hydrochlorothiazide and Hypertension, Essential studies

Hydrochlorothiazide: A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.
hydrochlorothiazide : A benzothiadiazine that is 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide substituted by a chloro group at position 6 and a sulfonamide at 7. It is diuretic used for the treatment of hypertension and congestive heart failure.

Research Excerpts

Excerpt	Relevance	Reference
"The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of metoprolol, telmisartan, and chlorthalidone in patients with essential hypertension and stable coronary artery disease (CAD) who showed inadequate response to dual therapy."	9.51	Fixed-dose Combination of Metoprolol, Telmisartan, and Chlorthalidone for Essential Hypertension in Adults with Stable Coronary Artery Disease: Phase III Study. ( Agrawal, S; Anand, J; Bachani, D; Doshi, M; Gaikwad, VB; Halder, SK; Kinholkar, B; Kumar, DA; Kumbhar, A; Mathur, R; Mehta, S; Sarkar, G; Sharma, A, 2022)
" Patients who met the criteria for essential hypertension (mean sitting systolic blood pressure [MSSBP], ≥140 and <200 mm Hg, or ≥130 and<200 mm Hg in those with diabetes mellitus or chronic kidney disease) after period 1 were randomly assigned to receive TA 40/5 mg + hydrochlorothiazide 12."	9.27	Efficacy and Tolerability of Telmisartan/Amlodipine + Hydrochlorothiazide Versus Telmisartan/Amlodipine Combination Therapy for Essential Hypertension Uncontrolled With Telmisartan/Amlodipine: The Phase III, Multicenter, Randomized, Double-blind TAHYTI St ( Ahn, JC; Ahn, JH; Ahn, YK; Cha, DH; Chae, IH; Cho, DK; Cho, SK; Choi, YJ; Hong, SJ; Hong, TJ; Hyon, MS; Jang, JY; Jeon, DW; Jeong, JO; Kim, BS; Kim, HS; Kim, SH; Nam, CW; Oh, YS; Park, SH; Rha, SW; Song, JM; Sung, KC; Won, KH; Yang, TH; Yoo, BS; Yoo, KD; Yoon, YW, 2018)
"Japanese patients with uncontrolled essential hypertension received single-blind losartan 50 mg/hydrochlorothiazide 12."	9.20	Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension. ( Azuma, K; Fujita, KP; Nishida, C; Numaguchi, H; Rakugi, H; Shimada, K; Shirakawa, M; Tsuchihashi, T; Yamaguchi, H, 2015)
"5)/amlodipine 5 mg (A5) versus co-administration of L50 plus A5 (L50+A5) in Japanese subjects with uncontrolled essential hypertension."	9.20	Add-on effect of hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension uncontrolled with losartan 50 mg and amlodipine 5 mg. ( Azuma, K; Fujita, KP; Nishida, C; Numaguchi, H; Rakugi, H; Shimada, K; Shirakawa, M; Tsuchihashi, T; Yamaguchi, H, 2015)
"A total of 48 patients with hypertension treated with 20 mg olmesartan were randomized to receive combination treatment with 16 mg azelnidipine (O/A group) or diuretics (1 mg indapamide; O/D group) for 12 months."	9.19	Effects of combination therapy with olmesartan and azelnidipine on serum osteoprotegerin in patients with hypertension. ( Amaya, N; Arakawa, K; Fukuoka, Y; Ishida, K; Lee, JD; Morishita, T; Nakano, A; Tada, H; Uzui, H, 2014)
"To assess the association of single nucleotide polymorphisms (SNPs) of STK39 gene with response to hydrochlorothiazide among ethnic Han Chinese patients with essential hypertension."	7.91	[Association of STK39 gene polymorphism with response to hydrochlorothiazide among ethnic Han Chinese with essential hypertension]. ( Cao, W; Du, H; Hou, W; Liu, M; Wang, X; Yu, S; Zhou, L, 2019)
"Most adverse events (AEs) were mild or moderate in intensity, and no deaths or treatment-related serious AEs were reported."	6.87	A phase III, open-label, multicenter study to evaluate the safety and efficacy of long-term triple combination therapy with azilsartan, amlodipine, and hydrochlorothiazide in patients with essential hypertension. ( Nishiyama, Y; Rakugi, H; Sano, Y; Shimizu, K; Umeda, Y, 2018)
" The adverse events (AEs) during both treatment periods were generally mild."	6.84	The efficacy and long-term safety of a triple combination of 80 mg telmisartan, 5 mg amlodipine and 12.5 mg hydrochlorothiazide in Japanese patients with essential hypertension: a randomized, double-blind study with open-label extension. ( Higaki, J; Ikeda, H; Komuro, I; Kuroki, D; Nishimura, S; Ogihara, T; Shiki, K; Taniguchi, A; Ugai, H, 2017)
" Drug-related adverse events with an incidence ⩾ 2% in the L100/H12."	6.79	Efficacy and safety of losartan 100 mg/hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension: two randomized, controlled trials. ( Azuma, K; Fujimoto, G; Fujita, KP; Hanson, ME; Nishida, C; Numaguchi, H; Rakugi, H; Shimada, K; Shirakawa, M; Tsuchihashi, T; Yamaguchi, H, 2014)
" Safety and tolerability were assessed by the incidence rate of adverse events (AEs) and discontinuation."	5.56	Real-World Effectiveness and Safety of a Single-Pill Combination of Olmesartan/Amlodipine/Hydrochlorothiazide in Korean Patients with Essential Hypertension (RESOLVE): A Large, Observational, Retrospective, Cohort Study. ( Park, SJ; Rhee, SJ, 2020)
"The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of metoprolol, telmisartan, and chlorthalidone in patients with essential hypertension and stable coronary artery disease (CAD) who showed inadequate response to dual therapy."	5.51	Fixed-dose Combination of Metoprolol, Telmisartan, and Chlorthalidone for Essential Hypertension in Adults with Stable Coronary Artery Disease: Phase III Study. ( Agrawal, S; Anand, J; Bachani, D; Doshi, M; Gaikwad, VB; Halder, SK; Kinholkar, B; Kumar, DA; Kumbhar, A; Mathur, R; Mehta, S; Sarkar, G; Sharma, A, 2022)
" Patients who met the criteria for essential hypertension (mean sitting systolic blood pressure [MSSBP], ≥140 and <200 mm Hg, or ≥130 and<200 mm Hg in those with diabetes mellitus or chronic kidney disease) after period 1 were randomly assigned to receive TA 40/5 mg + hydrochlorothiazide 12."	5.27	Efficacy and Tolerability of Telmisartan/Amlodipine + Hydrochlorothiazide Versus Telmisartan/Amlodipine Combination Therapy for Essential Hypertension Uncontrolled With Telmisartan/Amlodipine: The Phase III, Multicenter, Randomized, Double-blind TAHYTI St ( Ahn, JC; Ahn, JH; Ahn, YK; Cha, DH; Chae, IH; Cho, DK; Cho, SK; Choi, YJ; Hong, SJ; Hong, TJ; Hyon, MS; Jang, JY; Jeon, DW; Jeong, JO; Kim, BS; Kim, HS; Kim, SH; Nam, CW; Oh, YS; Park, SH; Rha, SW; Song, JM; Sung, KC; Won, KH; Yang, TH; Yoo, BS; Yoo, KD; Yoon, YW, 2018)
"This 52-week, randomized, open-label study evaluated long-term safety/tolerability of fixed-dose combination azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs fixed-dose combination olmesartan medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with essential hypertension (stage 2; clinic systolic blood pressure 160-190 mm Hg)."	5.24	Comparison of long-term safety of fixed-dose combinations azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide. ( Barger, B; Cushman, WC; Handley, A; Lloyd, E; Neutel, JM, 2017)
"In this randomized, open-label, controlled trial, we enrolled 175 Caucasian patients with essential hypertension not well controlled by concomitant ACE-I or ARBs and hydrochlorothiazide."	5.24	Efficacy and safety of two dosages of canrenone as add-on therapy in hypertensive patients taking ace-inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE-IT trial. ( Bestetti, A; D'Avino, M; Derosa, G; Felis, S; Gaudio, G; Guasti, L; Maffioli, P; Mugellini, A; Sala, C; Sarzani, R; Vanasia, M; Vulpis, V, 2017)
"Japanese patients with uncontrolled essential hypertension received single-blind losartan 50 mg/hydrochlorothiazide 12."	5.20	Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension. ( Azuma, K; Fujita, KP; Nishida, C; Numaguchi, H; Rakugi, H; Shimada, K; Shirakawa, M; Tsuchihashi, T; Yamaguchi, H, 2015)
" The Genetics of Drug Responsiveness in Essential Hypertension (GENRES) study is a double-blind, placebo-controlled cross-over study where each subject received amlodipine, bisoprolol,hydrochlorothiazide, and losartan, each as a monotherapy, in a randomized order."	5.20	Pharmacogenomics of hypertension: a genome‐wide, placebo‐controlled cross‐over study, using four classes of antihypertensive drugs. ( Boerwinkle, E; Chapman, AB; Cooper-DeHoff, RM; Donner, KM; Frau, F; Glorioso, N; Glorioso, V; Gong, Y; Gums, JG; Hiltunen, TP; Johnson, JA; Kontula, KK; Ripatti, S; Saarela, J; Salvi, E; Sarin, AP; Turner, ST; Zaninello, R, 2015)
"This exploratory study reports two plausible loci associated with SBP response to hydrochlorothiazide: TET2, an aldosterone-responsive mediator of αENaC gene transcription; and CSMD1, previously described as associated with hypertension in a case-control study."	5.20	TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives. ( Argiolas, G; Barlassina, C; Boerwinkle, E; Braga, D; Carpini, SD; Chapman, AB; Chittani, M; Citterio, L; Condorelli, G; Cooper-Dehoff, RM; Cusi, D; Dominiczak, AF; Donner, KM; Frau, F; Fresu, G; Glorioso, N; Glorioso, V; Gong, Y; Hiltunen, TP; Johnson, JA; Kontula, KK; Lanzani, C; Manunta, P; Melander, O; Ortu, MF; Padmanabhan, S; Piras, DA; Pozzoli, S; Rivera, NV; Salvi, E; Simonini, M; Trimarco, B; Troffa, C; Turner, ST; Velayutham, D; Zaninello, R, 2015)
"5)/amlodipine 5 mg (A5) versus co-administration of L50 plus A5 (L50+A5) in Japanese subjects with uncontrolled essential hypertension."	5.20	Add-on effect of hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension uncontrolled with losartan 50 mg and amlodipine 5 mg. ( Azuma, K; Fujita, KP; Nishida, C; Numaguchi, H; Rakugi, H; Shimada, K; Shirakawa, M; Tsuchihashi, T; Yamaguchi, H, 2015)
"A total of 48 patients with hypertension treated with 20 mg olmesartan were randomized to receive combination treatment with 16 mg azelnidipine (O/A group) or diuretics (1 mg indapamide; O/D group) for 12 months."	5.19	Effects of combination therapy with olmesartan and azelnidipine on serum osteoprotegerin in patients with hypertension. ( Amaya, N; Arakawa, K; Fukuoka, Y; Ishida, K; Lee, JD; Morishita, T; Nakano, A; Tada, H; Uzui, H, 2014)
"Our aim was to compare changes of vascular and metabolic parameters in patients with essential hypertension on treatment with combination of perindopril with either indapamide retard or hydrochlorothiazide."	5.19	[Direct comparison of endothelial and metabolic effects of perindopril combination with indapamide retard or hydrochlorothiazide]. ( Chindareva, OI; Nechaeva, GI; Pritykina, TV; Semenkin, AA; Stroeva, TV; Zhenatov, AB; Zhivilova, LA, 2014)
"These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension."	3.91	Effects of Different Antihypertensive Drug Combinations on Blood Pressure and Arterial Stiffness. ( Hebibovic, S; Jatic, Z; Rustempasic, E; Skopljak, A; Sukalo, A; Valjevac, A, 2019)
"To assess the association of single nucleotide polymorphisms (SNPs) of STK39 gene with response to hydrochlorothiazide among ethnic Han Chinese patients with essential hypertension."	3.91	[Association of STK39 gene polymorphism with response to hydrochlorothiazide among ethnic Han Chinese with essential hypertension]. ( Cao, W; Du, H; Hou, W; Liu, M; Wang, X; Yu, S; Zhou, L, 2019)
"Purpose - to improve antihypertensive therapy on the basis of studying the antioxidant properties of an angiotensin-converting enzyme (ACE) inhibitor (fosinopril sodium) and a diuretic (hydrochlorothiazide), their impact on endothelial dysfunction and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity."	3.85	PATHOGENETIC ADVANCES OF FOSINOPRIL SODIUM WITH HYDROCHLOROTHIAZIDE IN OBESE HYPERTENSIVE PATIENTS. ( Ashcheulova, T; Demydenko, G; Gerasimchuk, N; Kochubiei, O; Rezunenko, Y, 2017)
"Lercanidipine both in monotherapy and in combination with enalapril, was able to improve microvascular structure and to decrease central blood pressure, being thus a useful approach for both reducing blood pressure and improving vascular alterations in hypertension."	3.80	Effect of antihypertensive treatment on microvascular structure, central blood pressure and oxidative stress in patients with mild essential hypertension. ( Caimi, L; Cancarini, A; De Ciuceis, C; Duse, S; La Boria, E; Muiesan, ML; Paini, A; Ricotta, D; Rizzoni, D; Rosei, CA; Rosei, EA; Rossini, C; Ruggeri, G; Salvetti, M; Sarkar, A; Semeraro, F, 2014)
"A European multi-center, prospective, 24-week, non-interventional study was conducted including 14,979 patients with essential hypertension and new treatment with olmesartan, amlodipine and hydrochlorothiazide as an FDC."	3.80	Clinical impact of patient adherence to a fixed-dose combination of olmesartan, amlodipine and hydrochlorothiazide. ( Bramlage, P; Fronk, EM; Ketelhut, R; Schmieder, RE; Smolnik, R; Wolf, WP; Zemmrich, C, 2014)
"Adult patients with angiotensin receptor blocker (ARB)-resistant essential hypertension (n = 104) were enrolled and switched to combination therapy with losartan (50 mg/day) and hydrochlorothiazide (12."	3.79	Release from glomerular overload by the addition of low-dose thiazide in patients with angiotensin receptor blocker-resistant hypertension. ( Asakura, J; Hasegawa, H; Iwashita, T; Kawashima, K; Matsuda, A; Mitarai, T; Nakamura, T; Ogawa, T; Shimizu, T; Takayanagi, K; Tayama, Y, 2013)
"Most adverse events (AEs) were mild or moderate in intensity, and no deaths or treatment-related serious AEs were reported."	2.87	A phase III, open-label, multicenter study to evaluate the safety and efficacy of long-term triple combination therapy with azilsartan, amlodipine, and hydrochlorothiazide in patients with essential hypertension. ( Nishiyama, Y; Rakugi, H; Sano, Y; Shimizu, K; Umeda, Y, 2018)
" The adverse events (AEs) during both treatment periods were generally mild."	2.84	The efficacy and long-term safety of a triple combination of 80 mg telmisartan, 5 mg amlodipine and 12.5 mg hydrochlorothiazide in Japanese patients with essential hypertension: a randomized, double-blind study with open-label extension. ( Higaki, J; Ikeda, H; Komuro, I; Kuroki, D; Nishimura, S; Ogihara, T; Shiki, K; Taniguchi, A; Ugai, H, 2017)
" Adverse events (AEs) were reported in 75."	2.82	Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study. ( Barger, B; Handley, A; Lloyd, E; Roberts, A, 2016)
" Drug-related adverse events with an incidence ⩾ 2% in the L100/H12."	2.79	Efficacy and safety of losartan 100 mg/hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension: two randomized, controlled trials. ( Azuma, K; Fujimoto, G; Fujita, KP; Hanson, ME; Nishida, C; Numaguchi, H; Rakugi, H; Shimada, K; Shirakawa, M; Tsuchihashi, T; Yamaguchi, H, 2014)
"Hypertension is a modifiable cardiovascular risk factor."	2.50	Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. ( Bassett, K; Musini, VM; Nazer, M; Wright, JM, 2014)
" Safety and tolerability were assessed by the incidence rate of adverse events (AEs) and discontinuation."	1.56	Real-World Effectiveness and Safety of a Single-Pill Combination of Olmesartan/Amlodipine/Hydrochlorothiazide in Korean Patients with Essential Hypertension (RESOLVE): A Large, Observational, Retrospective, Cohort Study. ( Park, SJ; Rhee, SJ, 2020)

Research

Studies (37)

Authors

Clinical Trials (11)

Trial Overview

Trial Outcomes

Change From Baseline in Home Sitting Clinic Systolic and Diastolic Blood Pressure at Each Visit

Timeframe	Studies, this research(%)	All Research%
pre-1990	6 (16.22)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	27 (72.97)	24.3611
2020's	4 (10.81)	2.80

Authors	Studies
Sarkar, G	1
Gaikwad, VB	1
Sharma, A	2
Halder, SK	1
Kumar, DA	1
Anand, J	1
Agrawal, S	1
Kumbhar, A	1
Kinholkar, B	1
Mathur, R	1
Doshi, M	1
Bachani, D	1
Mehta, S	1
Xie, M	1
Tang, T	1
Liang, H	1
Jatic, Z	1
Skopljak, A	1
Hebibovic, S	1
Sukalo, A	1
Rustempasic, E	1
Valjevac, A	1
Lee, JW	1
Choi, E	1
Son, JW	1
Youn, YJ	1
Ahn, SG	1
Ahn, MS	1
Kim, JY	1
Lee, SH	1
Yoon, J	1
Ryu, DR	1
Park, SM	1
Hong, KS	1
Yoo, BS	2
Park, SJ	1
Rhee, SJ	1
Neutel, JM	1
Cushman, WC	1
Lloyd, E	2
Barger, B	2
Handley, A	2
Ashcheulova, T	1
Gerasimchuk, N	1
Rezunenko, Y	1
Demydenko, G	1
Kochubiei, O	1
Rakugi, H	5
Shimizu, K	2
Nishiyama, Y	2
Sano, Y	2
Umeda, Y	1
Kinugawa, Y	1
Terashio, S	1
Sung, KC	1
Oh, YS	1
Cha, DH	1
Hong, SJ	1
Won, KH	1
Yoo, KD	1
Rha, SW	1
Ahn, YK	1
Ahn, JC	1
Jang, JY	1
Hong, TJ	1
Cho, SK	1
Park, SH	1
Hyon, MS	2
Nam, CW	1
Chae, IH	1
Song, JM	1
Jeong, JO	1
Yoon, YW	1
Kim, BS	1
Yang, TH	1
Cho, DK	1
Kim, SH	1
Choi, YJ	1
Ahn, JH	1
Jeon, DW	1
Kim, HS	1
Ahn, Y	1
Kim, Y	1
Chang, K	1
Kim, W	1
Rhee, MY	1
Cha, KS	1
Shim, CY	1
Lee, SY	1
Kim, DI	1
Kim, SW	1
Lim, SW	1
Han, KR	1
Jo, SH	1
Lee, NH	1
Kwan, J	1
Ahn, T	1
Hou, W	1
Liu, M	1
Yu, S	1
Wang, X	1
Du, H	1
Zhou, L	1
Cao, W	1
Hiremath, JS	1
Chokalingam, K	1
Mathan, G	1
Reddy, PNC	1
Dhawan, S	1
Toppo, A	1
Chapman, AB	3
Cotsonis, G	1
Parekh, V	1
Schwartz, GL	1
Gong, Y	3
Bailey, KR	1
Turner, ST	3
Gums, JG	2
Beitelshees, AL	1
Cooper-DeHoff, R	1
Boerwinkle, E	3
Johnson, JA	3
Hasegawa, H	1
Tayama, Y	1
Takayanagi, K	1
Asakura, J	1
Nakamura, T	1
Kawashima, K	1
Shimizu, T	1
Iwashita, T	1
Ogawa, T	1
Matsuda, A	1
Mitarai, T	1
Uzui, H	1
Morishita, T	1
Nakano, A	1
Amaya, N	1
Fukuoka, Y	1
Ishida, K	1
Arakawa, K	1
Lee, JD	1
Tada, H	1
De Ciuceis, C	1
Salvetti, M	1
Rossini, C	1
Muiesan, ML	1
Paini, A	1
Duse, S	1
La Boria, E	1
Semeraro, F	1
Cancarini, A	1
Rosei, CA	1
Sarkar, A	1
Ruggeri, G	1
Caimi, L	1
Ricotta, D	1
Rizzoni, D	1
Rosei, EA	1
Bramlage, P	1
Ketelhut, R	1
Fronk, EM	1
Wolf, WP	1
Smolnik, R	1
Zemmrich, C	1
Schmieder, RE	1
Musini, VM	1
Nazer, M	1
Bassett, K	1
Wright, JM	1
Tsuchihashi, T	3
Shimada, K	3
Numaguchi, H	3
Nishida, C	3
Yamaguchi, H	3
Fujimoto, G	1
Azuma, K	3
Shirakawa, M	3
Hanson, ME	1
Fujita, KP	3
Hiltunen, TP	2
Donner, KM	2
Sarin, AP	1
Saarela, J	1
Ripatti, S	1
Cooper-DeHoff, RM	2
Frau, F	2
Glorioso, V	2
Zaninello, R	2
Salvi, E	2
Glorioso, N	2
Kontula, KK	2
Chittani, M	1
Lanzani, C	1
Ortu, MF	1
Fresu, G	1
Citterio, L	1
Braga, D	1
Piras, DA	1
Carpini, SD	1
Velayutham, D	1
Simonini, M	1
Argiolas, G	1
Pozzoli, S	1
Troffa, C	1
Padmanabhan, S	1
Dominiczak, AF	1
Melander, O	1
Rivera, NV	1
Condorelli, G	1
Trimarco, B	1
Manunta, P	1
Cusi, D	1
Barlassina, C	1
Semenkin, AA	1
Zhenatov, AB	1
Zhivilova, LA	1
Nechaeva, GI	1
Pritykina, TV	1
Chindareva, OI	1
Stroeva, TV	1
Wang, J	1
Qiu, B	1
Du, JL	1
Deng, SB	1
Liu, YJ	1
She, Q	1
MacDonald, TM	2
Williams, B	2
Caulfield, M	2
Cruickshank, JK	2
McInnes, G	2
Sever, P	2
Webb, DJ	2
Mackenzie, IS	1
Salsbury, J	2
Morant, S	2
Ford, I	2
Brown, MJ	2
Roberts, A	1
Higaki, J	1
Komuro, I	1
Shiki, K	1
Ugai, H	1
Taniguchi, A	1
Ikeda, H	1
Kuroki, D	1
Nishimura, S	1
Ogihara, T	1
Derosa, G	1
Maffioli, P	1
D'Avino, M	1
Sala, C	1
Mugellini, A	1
Vulpis, V	1
Felis, S	1
Guasti, L	1
Sarzani, R	1
Bestetti, A	1
Vanasia, M	1
Gaudio, G	1
FURBETTA, D	1
SANTUCCI, F	1
BREST, AN	1
ONESTI, G	1
SEKINE, G	1
SELLER, R	1
MOYER, JH	1
GLAUBITT, D	1
RAUSCH-STROOMANN, JG	1
WILSON, WR	1
OKUN, R	1
TETREAULT, L	1
NANAVATY, JM	1
KAMAT, GR	1
CARTER, FS	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase 3, Open-label, Multicenter, Long-term Study to Evaluate the Safety and Efficacy of TAK-536, Amlodipine and Hydrochlorothiazide in Subjects With Essential Hypertension[NCT02277691]	Phase 3	341 participants (Actual)	Interventional	2014-11-07	Completed
Randomized, Double-Blind, Multi-Center, Phase 3 Trial to Evaluate the Efficacy and Safety of Telmisartan/Amlodipine/Hydrochlorothiazide Combination in Comparison With Telmisartan/Amlodipine Combination for Essential Hypertension Patients Not Controlled by[NCT02738632]	Phase 3	300 participants (Anticipated)	Interventional	2015-05-31	Completed
Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR)[NCT00246519]	Phase 4	1,701 participants (Actual)	Interventional	2005-10-31	Completed
A Phase III, Randomized, Active-comparator Controlled Clinical Trial to Study the Efficacy and Safety of MK-0954A in Japanese Patients With Essential Hypertension Uncontrolled With the High Dose of Losartan Potassium[NCT01307046]	Phase 3	336 participants (Actual)	Interventional	2011-03-29	Completed
A Phase III, Randomized, Active-comparator Controlled and a Long-term Clinical Trial to Study the Safety of MK-0954A (L100/H12.5 mg) in Japanese Patients With Essential Hypertension Uncontrolled With MK-954H (L50/H12.5 mg) [PREMINENT®][NCT01307033]	Phase 3	278 participants (Actual)	Interventional	2011-03-29	Completed
A Phase III, Randomized, Active-Comparator Controlled Clinical Trial to Study the Efficacy and Safety of MK-0954E in Japanese Patients With Essential Hypertension Uncontrolled With Losartan and Amlodipine Co-administration[NCT01302691]	Phase 3	327 participants (Actual)	Interventional	2011-01-01	Completed
A Phase III, Randomized, Active-Comparator Controlled Clinical Trial to Study the Efficacy and Safety of MK-0954E in Japanese Patients With Essential Hypertension Uncontrolled With MK-954H (L50/H12.5 mg) [PREMINENT®] and an Open-label, Long-term Clinical [NCT01299376]	Phase 3	286 participants (Actual)	Interventional	2011-01-24	Completed
A Randomised Double-blind Cross-over Single-centre Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension[NCT03276598]	Phase 4	233 participants (Actual)	Interventional	1999-11-25	Completed
Increasing Stay-on-therapy in Hypertensive Patients Treated With First-line Diuretics: An Active Pharmacosurveillance and Pharmacogenetic Study.[NCT00408512]	Phase 4	2,500 participants (Anticipated)	Interventional	2006-12-31	Completed
Comparison of Single and Combination Diuretics in Low-Renin Hypertension[NCT02351973]	Phase 4	423 participants (Actual)	Interventional	2009-11-30	Active, not recruiting
Efficacy and Safety of Canrenone as Add-on in Patients With Essential Hypertension-Italy (ESCAPE-IT)[NCT02687178]	Phase 4	180 participants (Actual)	Interventional	2010-10-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The change in home morning SPB and DBP measured at End of Week 12, End of Treatment (Up to Week 52) relative to baseline. (NCT02277691)
Timeframe: Baseline (End of Run-in Period, Week 0), End of Week 12 and End of Treatment (Up to Week 52)

Change From Baseline in Office Trough Sitting Clinic Systolic and Diastolic Blood Pressure at Each Visit

Intervention	mmHg (Mean)
	Change at End of Week 12, Morning SBP	Change at EOT (Up to Week 52), Morning SBP	Change at End of Week 12, Morning DBP	Change at EOT (Up to Week 52), Morning DBP
TAK-536TCH	-13.9	-12.4	-7.9	-6.9

The change in office trough SBP and DBP measured at Weeks 12 last observation was carried forward (LOCF) and 52 (LOCF) relative to baseline. Sitting blood pressure was measured at least 3 times. Each measurement session ended once blood pressure was found stable at 2 consecutive measurements. The average of the last 2 measurements of office sitting blood pressure was used. (NCT02277691)
Timeframe: Baseline (End of Run-in Period, Week 0) and Weeks 12 (LOCF) and 52 (LOCF)

Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Intervention	mmHg (Mean)
	Change at Week 12 (LOCF), SBP	Change at Week 52 (LOCF), SBP	Change at Week 12 (LOCF), DBP	Change at Week 52 (LOCF), DBP
TAK-536TCH	-14.4	-13.9	-8.6	-8.3

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. (NCT02277691)
Timeframe: Baseline up to Week 52

Number of Participants With Markedly Abnormal Clinical Laboratory Tests

Intervention	Participants (Count of Participants)
	TEAEs	SAEs
TAK-536TCH	289	20

The number of participants with any markedly abnormal clinical laboratory test values collected throughout study. RBC = Red blood cells, ALT = alanine aminotransferase, AST = aspartate aminotransferase, GGT = gamma-glutamyl transferase, LLN = lower limit of normal or lower reference limit, ULN = upper limit of normal or upper reference limit. Laboratory vallues were considered abnormal if they were beyond the values defined in categories. (NCT02277691)
Timeframe: Baseline up to Week 52

Number of Participants With Markedly Abnormal Vital Signs Values

Intervention	Participants (Count of Participants)
	RBC (< 0.8×LLN×10^6cells/μL)	Hemoglobin (<0.8 × LLN g/dL)	Hematocrit (<0.8 × LLN Percent)	ALT (>3 × ULN U/L)	AST (>3 × ULN U/L)	Total Bilirubin (>2.0 mg/dL)	Creatinine (>2.0 mg/dL)	Blood Urea Nitrogen (>30 mg/dL)	GGT (>3 × ULN U/L)	Eosinophils (>2 × ULN×10^3cells/μL)	Uric Acid (>13.0 mg/dL)	Total Cholesterol (>300 mg/dL)	Triglycerides (>2.5 × ULN mg/dL)	Potassium (<3.0 mEq/L)	Sodium (<130 mEq/L)
TAK-536TCH	5	2	2	4	4	2	1	20	14	4	1	2	29	3	3

Vital signs included supine and standing systolic and diastolic blood pressure (SBP and DBP) respectively and office sitting pulse. Vital signs were considered abnormal if they were beyond the values defined in categories. (NCT02277691)
Timeframe: Baseline up to Week 52

Number of Participants With Treatment Emergent Adverse Event (TEAE) Related to Body Weight

Intervention	Participants (Count of Participants)
	SBP (Supine) (>180mmHg)	SBP (Standing) (<85mmHg)	SBP (Standing) (>180mmHg)	DBP (Supine) (<50mmHg)	DBP (Standing) (>110mmHg)	Office, Sitting Pulse (<50bpm)
TAK-536TCH	1	1	3	2	4	10

Reported TEAE is categorized into investigations System Organ Class (SOC) related to body weight. (NCT02277691)
Timeframe: Baseline up to Week 52

Number of Participants With Treatment Emergent Adverse Event (TEAE) Related to Electrocardiogram (ECG)

Intervention	Participants (Count of Participants)
	Weight decreased	Weight increased
TAK-536TCH	2	2

Reported TEAE is categorized into cardiac disorders and investigations system organ class (SOC) related to ECG. (NCT02277691)
Timeframe: Baseline up to Week 52

Blood Pressure Response (Delta BP (After 18 Weeks of Medication - Baseline)).

Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP)

Intervention	Participants (Count of Participants)
	Atrial fibrillation	Sinus bradycardia	QRS axis abnormal
TAK-536TCH	3	1	1

Intervention	mmHg (Mean)
Atenolol +HCTZ Arm	-12.06
HCTZ + Atenolol	-13.33

Sitting diastolic blood pressure was measured by automated sphygmomanometer pre-dose on Day 1 (baseline) and at 24 ± 2 hours after the last study drug administration (Day 56 ± 7 days). (NCT01307046)
Timeframe: Baseline and Week 8

Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP)

Intervention	mmHg (Least Squares Mean)
MK-0954A	-8.7
Losartan	-3.6

Sitting systolic blood pressure was measured by automated sphygmomanometer pre-dose on Day 1 (baseline) and at 24 ± 2 hours after the last study drug administration (Day 56 ± 7 days). (NCT01307046)
Timeframe: Baseline and Week 8

Percentage of Participants Who Experienced at Least One Adverse Event (AE)

Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8

Intervention	mmHg (Least Squares Mean)
MK-0954A	-14.5
Losartan	-5.4

Intervention	percentage of participants (Number)
MK-0954A	31.3
Losartan	26.5

Blood pressure (BP) was measured with an automatic sphygmomanometer after participant has been resting in a sitting position for at least 10 minutes. BP was determined averaging 3 replicate measurements obtained at least a 1- to 2-minute interval between BP measurements. The recorded BP was the calculated average of the 3 readings. (NCT01307033)
Timeframe: Baseline and Week 8 (End of Double-blind Period)

Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8

Intervention	mmHg (Least Squares Mean)
MK-0954H (L50/H12.5)	-5.3
MK-0954A (L100/H12.5)	-5.0

Percentage of Participants Who Experienced an Adverse Event When Receiving MK-0954A (L100/H12.5) During Study (8-week Double-blind and/or 44-week Open-label Extension)

Change in Mean Trough Sitting Diastolic Blood Pressure (SiDBP)

Intervention	mmHg (Least Squares Mean)
MK-0954H (L50/H12.5)	-6.2
MK-0954A (L100/H12.5)	-8.5

Intervention	Percentage of Participants (Number)
L50/H12.5→L100/H12.5 Open Label (Period 2)	71.0
L100/H12.5→L100/H12.5 Open Label (Period 2)	72.4

Sitting diastolic blood pressure was measured by automated sphygmomanometer pre-dose on Day 1 (baseline) and at 24 ± 2 hours after the last study drug administration at Week 8. The difference between the baseline and Week 8 assessments was calculated and summarized by treatment arm. (NCT01302691)
Timeframe: Baseline and Week 8

Change in Mean Trough Sitting Systolic Blood Pressure (SiSBP)

Intervention	mmHg (Least Squares Mean)
L50/H12.5/A5	-9.1
L50 + A5	-8.0

Sitting systolic blood pressure was measured by automated sphygmomanometer pre-dose on Day 1 (baseline) and at 24 ± 2 hours after the last study drug administration at Week 8. The difference between the baseline and Week 8 assessments was calculated and summarized by treatment arm. (NCT01302691)
Timeframe: Baseline and Week 8

Percentage of Participants Who Experience ≥1 Adverse Event (AE)

Intervention	mmHg (Least Squares Mean)
L50/H12.5/A5	-13.4
L50 + A5	-10.2

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who experienced at least 1 AE during the 10-week treatment and follow-up period were summarized by study drug received. (NCT01302691)
Timeframe: up to 14 days after last dose of study drug (up to 10 weeks)

Percentage of Participants Who Experience ≥1 Drug-related AE

Intervention	Percentage of Participants (Number)
L50/H12.5/A5	30.5
L50 + A5	28.8

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. Percentage of participants that experienced at least 1 AE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the 10-week treatment and follow-up period were summarized by study drug received. (NCT01302691)
Timeframe: up to 14 days after last dose of study drug (up to 10 weeks)

Percentage of Participants Who Experience ≥1 Drug-related SAE

Intervention	Percentage of Participants (Number)
L50/H12.5/A5	11.6
L50 + A5	3.7

An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. Percentage of participants that experienced at least 1 SAE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the 10-week treatment and follow-up period were summarized by study drug received (NCT01302691)
Timeframe: up to 14 days after last dose of study drug (up to 10 weeks)

Percentage of Participants Who Experience ≥1 Serious Adverse Event (SAE)

Intervention	Percentage of Participants (Number)
L50/H12.5/A5	0.0
L50 + A5	0.0

An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. The percentage of participants who experienced at least 1 SAE during the 10-week treatment and follow-up period were summarized by study drug received. (NCT01302691)
Timeframe: up to 14 days after last dose of study drug (up to 10 weeks)

Percentage of Participants Who Had Study Drug Stopped Due to an AE

Intervention	Percentage of Participants (Number)
L50/H12.5/A5	0.6
L50 + A5	0.6

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who had study drug stopped during the 8-week treatment period due to an AE regardless of whether or not they completed the study was summarized by treatment arm (NCT01302691)
Timeframe: up to 8 weeks

Change in Trough Sitting Diastolic Blood Pressure (SiDBP)-Double-Blind Treatment Period

Intervention	Percentage of Participants (Number)
L50/H12.5/A5	1.2
L50 + A5	0.0

Change in Trough Sitting Systolic Blood Pressure (SiSBP)-Double-Blind Treatment Period

Intervention	mmHg (Least Squares Mean)
L50/H12.5/A5	-12.1
L50/H12.5	-6.2

Sitting systolic blood pressure was measured by automated sphygmomanometer pre-dose on Day 1 (baseline) and at 24 ± 2 hours after the last study drug administration at Week 8. (NCT01299376)
Timeframe: Baseline and Week 8

Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Double-Blind Treatment Period

Intervention	mmHg (Least Squares Mean)
L50/H12.5/A5	-17.7
L50/H12.5	-7.5

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who experienced at least 1 AE during the 8-week double-blind treatment period were summarized by study drug received. (NCT01299376)
Timeframe: up to Week 8

Percentage of Participants Who Experience 1 or More Adverse Events (AEs)- Long Term

Intervention	Percentage of Participants (Number)
L50/H12.5/A5	27.0
L50/H12.5	29.7

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants that experienced at least 1 AE during long-term period was summarized. (NCT01299376)
Timeframe: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5

Percentage of Participants Who Experience 1 or More Drug-Related AEs- Double-Blind Treatment Period

Intervention	Percentage of Participants (Number)
L50/H12.5/A5→L50/H12.5/A5	70.9
L50/H12.5→L50/H12.5/A5	66.2

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. Percentage of participants that experienced at least 1 AE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the 8-week double-blind treatment period were summarized by study drug received. (NCT01299376)
Timeframe: up to Week 8

Percentage of Participants Who Experience 1 or More Drug-related AEs- Long Term

Intervention	Percentage of Participants (Number)
L50/H12.5/A5	12.1
L50/H12.5	14.5

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. Percentage of participants that experienced at least 1 AE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the long-term reporting period was summarized. (NCT01299376)
Timeframe: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5

Percentage of Participants Who Experience 1 or More Drug-related SAEs- Long Term

Intervention	Percentage of Participants (Number)
L50/H12.5/A5→L50/H12.5/A5	27.7
L50/H12.5→L50/H12.5/A5	14.3

An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. the percentage of participants that experienced an SAE that assessed as possibly, probably, or definitely related to the study drug by the investigator was summarized. (NCT01299376)
Timeframe: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5

Percentage of Participants Who Experience 1 or More Drug-Related Serious Adverse Events (SAEs)- Double-Blind Treatment Period

Intervention	Percentage of Participants (Number)
L50/H12.5/A5→L50/H12.5/A5	0.0
L50/H12.5→L50/H12.5/A5	0.8

An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. Percentage of participants that experienced at least 1 SAE that was reported as possibly, probably, or definitely related to the study drug by the investigator during the 8-week double-blind treatment period were summarized by study drug received. (NCT01299376)
Timeframe: up to Week 8

Percentage of Participants Who Experience 1 or More SAEs- Long Term

Intervention	Percentage of Participants (Number)
L50/H12.5/A5	0.0
L50/H12.5	0.0

An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. Those SAEs assessed as possibly, probably, or definitely related to the study drug during the long-term period were summarized. (NCT01299376)
Timeframe: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5

Percentage of Participants Who Experience 1 or Serious Adverse Events (SAEs)- Double-Blind Treatment Period

Intervention	Percentage of Participants (Number)
L50/H12.5/A5→L50/H12.5/A5	2.1
L50/H12.5→L50/H12.5/A5	3.0

An SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. The percentage of participants who experienced at least 1 SAE during the 8-week double-blind treatment period were summarized by study drug received. (NCT01299376)
Timeframe: up to Week 8

Percentage of Participants Who Had Study Drug Discontinued Due to an AE - Double Blind Treatment Period

Intervention	Percentage of Participants (Number)
L50/H12.5/A5	0.7
L50/H12.5	1.4

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who had study drug stopped during the 8-week double-blind treatment period due to an AE regardless of whether or not they completed the study was summarized by treatment arm. (NCT01299376)
Timeframe: up to Week 8

Percentage of Participants Who Had Study Drug Discontinued From the Study Due to an AE- Long Term

Intervention	Percentage of Participants (Number)
L50/H12.5/A5	0.7
L50/H12.5	1.4

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who had study drug discontinued during the 44 week extension due to an AE regardless of completion status were summarized. (NCT01299376)
Timeframe: Week 9 up to Week 52 for L50/H12.5→L50/H12.5/A5 arm; Week 1 to Week 52 for L50/H12.5/A5→L50/H12.5/A5

Article	Year
Efficacy of single-pill combination in uncontrolled essential hypertension: A systematic review and network meta-analysis. Clinical cardiology, 2023, Volume: 46, Issue:8 Topics: Amlodipine; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihyperten	2023
Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. The Cochrane database of systematic reviews, 2014, May-29, Issue:5 Topics: Adult; Antihypertensive Agents; Blood Pressure; Chlorthalidone; Essential Hypertension; Humans; Hydr	2014

Article	Year
Fixed-dose Combination of Metoprolol, Telmisartan, and Chlorthalidone for Essential Hypertension in Adults with Stable Coronary Artery Disease: Phase III Study. Advances in therapy, 2022, Volume: 39, Issue:2 Topics: Adult; Amlodipine; Antihypertensive Agents; Blood Pressure; Chlorthalidone; Coronary Artery Disease;	2022
Comparison of Blood Pressure Variability Between Losartan and Amlodipine in Essential Hypertension (COMPAS-BPV). American journal of hypertension, 2020, 08-04, Volume: 33, Issue:8 Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Essenti	2020
Comparison of long-term safety of fixed-dose combinations azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide. Journal of clinical hypertension (Greenwich, Conn.), 2017, Volume: 19, Issue:9 Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimida	2017
A phase III, open-label, multicenter study to evaluate the safety and efficacy of long-term triple combination therapy with azilsartan, amlodipine, and hydrochlorothiazide in patients with essential hypertension. Blood pressure, 2018, Volume: 27, Issue:3 Topics: Adult; Aged; Amlodipine; Benzimidazoles; Blood Pressure; Drug Administration Schedule; Drug Therapy,	2018
Effects of triple combination therapy with azilsartan/amlodipine/hydrochlorothiazide on office/home blood pressure: a randomized-controlled trial in Japanese essential hypertensive patients. Blood pressure monitoring, 2018, Volume: 23, Issue:2 Topics: Aged; Amlodipine; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Double-Blind Method; Drug	2018
Efficacy and Tolerability of Telmisartan/Amlodipine + Hydrochlorothiazide Versus Telmisartan/Amlodipine Combination Therapy for Essential Hypertension Uncontrolled With Telmisartan/Amlodipine: The Phase III, Multicenter, Randomized, Double-blind TAHYTI St Clinical therapeutics, 2018, Volume: 40, Issue:1 Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood Pressure; Dizzine	2018
A multicenter, randomized, and double-blind phase IV clinical trial to compare the efficacy and safety of fixed-dose combinations of amlodipine orotate/valsartan 5/160 mg versus valsartan/hydrochlorothiazide 160/12.5 mg in patients with essential hyperten Medicine, 2018, Volume: 97, Issue:37 Topics: Aged; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Double-Blind	2018
A Randomized, Double-blinded, Controlled, Multicentre Phase III Study to Evaluate the Efficacy and Safety of Telmisartan /Amlodipine/Hydrochlorothiazide Compared to Telmisartan/Hydrochlorothiazide in Patients with Essential Hypertension. The Journal of the Association of Physicians of India, 2018, Volume: 66, Issue:12 Topics: Amlodipine; Antihypertensive Agents; Drug Combinations; Drug Therapy, Combination; Essential Hyperte	2018
Night blood pressure responses to atenolol and hydrochlorothiazide in black and white patients with essential hypertension. American journal of hypertension, 2014, Volume: 27, Issue:4 Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Atenolol; Black People; Blood Pressure; Blood Pres	2014
Effects of combination therapy with olmesartan and azelnidipine on serum osteoprotegerin in patients with hypertension. Journal of cardiovascular pharmacology and therapeutics, 2014, Volume: 19, Issue:3 Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Azetidine	2014
Efficacy and safety of losartan 100 mg/hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension: two randomized, controlled trials. Hypertension research : official journal of the Japanese Society of Hypertension, 2014, Volume: 37, Issue:12 Topics: Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; As	2014
Efficacy and safety of losartan 100 mg/hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension: two randomized, controlled trials. Hypertension research : official journal of the Japanese Society of Hypertension, 2014, Volume: 37, Issue:12 Topics: Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; As	2014
Efficacy and safety of losartan 100 mg/hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension: two randomized, controlled trials. Hypertension research : official journal of the Japanese Society of Hypertension, 2014, Volume: 37, Issue:12 Topics: Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; As	2014
Efficacy and safety of losartan 100 mg/hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension: two randomized, controlled trials. Hypertension research : official journal of the Japanese Society of Hypertension, 2014, Volume: 37, Issue:12 Topics: Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; As	2014
Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension. Clinical and experimental hypertension (New York, N.Y. : 1993), 2015, Volume: 37, Issue:3 Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Combinations; Drug Monitoring; Essen	2015
Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension. Clinical and experimental hypertension (New York, N.Y. : 1993), 2015, Volume: 37, Issue:3 Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Combinations; Drug Monitoring; Essen	2015
Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension. Clinical and experimental hypertension (New York, N.Y. : 1993), 2015, Volume: 37, Issue:3 Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Combinations; Drug Monitoring; Essen	2015
Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension. Clinical and experimental hypertension (New York, N.Y. : 1993), 2015, Volume: 37, Issue:3 Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Combinations; Drug Monitoring; Essen	2015
Pharmacogenomics of hypertension: a genome‐wide, placebo‐controlled cross‐over study, using four classes of antihypertensive drugs. Journal of the American Heart Association, 2015, Jan-26, Volume: 4, Issue:1 Topics: Adult; Aldehyde Oxidoreductases; Amlodipine; Antihypertensive Agents; Benzimidazoles; Biphenyl Compo	2015
TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives. Journal of hypertension, 2015, Volume: 33, Issue:6 Topics: Adult; Aged; Aldosterone; Antihypertensive Agents; Blood Pressure; Case-Control Studies; Dioxygenase	2015
Add-on effect of hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension uncontrolled with losartan 50 mg and amlodipine 5 mg. Hypertension research : official journal of the Japanese Society of Hypertension, 2015, Volume: 38, Issue:5 Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Blood Pressure; Double-Blind Me	2015
[Direct comparison of endothelial and metabolic effects of perindopril combination with indapamide retard or hydrochlorothiazide]. Kardiologiia, 2014, Volume: 54, Issue:11 Topics: Aged; Antihypertensive Agents; Biological Availability; Blood Pressure; Carbohydrate Metabolism; Del	2014
The effects of a low-salt diet on the efficacy of different antihypertensive drug regimens. Journal of clinical pharmacology, 2015, Volume: 55, Issue:12 Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Diet, Sodium-R	2015
Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial. BMJ open, 2015, Aug-07, Volume: 5, Issue:8 Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulat	2015
Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension. BMJ open, 2015, Aug-07, Volume: 5, Issue:8 Topics: Adolescent; Adult; Aged; Amiloride; Blood Glucose; Blood Pressure; Clinical Protocols; Diuretics; Do	2015
Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study. Clinical and experimental hypertension (New York, N.Y. : 1993), 2016, Volume: 38, Issue:2 Topics: Adult; Aged; Benzimidazoles; Chlorthalidone; Cohort Studies; Dizziness; Drug Therapy, Combination; E	2016
The efficacy and long-term safety of a triple combination of 80 mg telmisartan, 5 mg amlodipine and 12.5 mg hydrochlorothiazide in Japanese patients with essential hypertension: a randomized, double-blind study with open-label extension. Hypertension research : official journal of the Japanese Society of Hypertension, 2017, Volume: 40, Issue:1 Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood Pressure; Double-	2017
Efficacy and safety of two dosages of canrenone as add-on therapy in hypertensive patients taking ace-inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE-IT trial. Cardiovascular therapeutics, 2017, Volume: 35, Issue:1 Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihyperte	2017

Article	Year
Effects of Different Antihypertensive Drug Combinations on Blood Pressure and Arterial Stiffness. Medical archives (Sarajevo, Bosnia and Herzegovina), 2019, Volume: 73, Issue:3 Topics: Aged; Amlodipine; Antihypertensive Agents; Arteries; Blood Pressure; Diastole; Drug Combinations; Es	2019
Real-World Effectiveness and Safety of a Single-Pill Combination of Olmesartan/Amlodipine/Hydrochlorothiazide in Korean Patients with Essential Hypertension (RESOLVE): A Large, Observational, Retrospective, Cohort Study. Advances in therapy, 2020, Volume: 37, Issue:8 Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Asian People; Cohort Studies; D	2020
PATHOGENETIC ADVANCES OF FOSINOPRIL SODIUM WITH HYDROCHLOROTHIAZIDE IN OBESE HYPERTENSIVE PATIENTS. Georgian medical news, 2017, Issue:271 Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Case-Control Studies	2017
[Association of STK39 gene polymorphism with response to hydrochlorothiazide among ethnic Han Chinese with essential hypertension]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics, 2019, Jun-10, Volume: 36, Issue:6 Topics: Asian People; Essential Hypertension; Genotype; Humans; Hydrochlorothiazide; Polymorphism, Single Nu	2019
Release from glomerular overload by the addition of low-dose thiazide in patients with angiotensin receptor blocker-resistant hypertension. Kidney & blood pressure research, 2013, Volume: 37, Issue:6 Topics: Aged; Aged, 80 and over; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Dose-Response Relatio	2013
Effect of antihypertensive treatment on microvascular structure, central blood pressure and oxidative stress in patients with mild essential hypertension. Journal of hypertension, 2014, Volume: 32, Issue:3 Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arterioles; Blood Pressure	2014
Clinical impact of patient adherence to a fixed-dose combination of olmesartan, amlodipine and hydrochlorothiazide. Clinical drug investigation, 2014, Volume: 34, Issue:6 Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Combinations; Essential Hyper	2014
[Treatment of severe essential arterial hypertension with combined reserpine and hydrochlorothiazide]. Il Policlinico. Sezione pratica, 1960, Feb-29, Volume: 67 Topics: Antihypertensive Agents; Chlorothiazide; Essential Hypertension; Hydrochlorothiazide; Hypertension;	1960
Meprobamate alone and in combination with hydrochlorothiazide in the treatment of essential hypertension. Current therapeutic research, clinical and experimental, 1962, Volume: 4 Topics: Chlorothiazide; Essential Hypertension; Hydrochlorothiazide; Hypertension; Meprobamate	1962
[Magnesium, calcium and phosphorus balances in essential hypertension and heart insufficiency in the treatment with hydrochlorothiazide]. Klinische Wochenschrift, 1962, Feb-01, Volume: 40 Topics: Calcium, Dietary; Chlorothiazide; Essential Hypertension; Heart Failure; Humans; Hydrochlorothiazide	1962
METHYLDOPA AND HYDROCHLOROTHIAZIDE IN PRIMARY HYPERTENSION: CONTROLLED CLINICAL TRIAL OF DRUGS SINGLY AND IN COMBINATION. JAMA, 1963, Sep-14, Volume: 185 Topics: Antihypertensive Agents; Essential Hypertension; Humans; Hydrochlorothiazide; Hypertension; Methyldo	1963
CLINICAL EXPERIENCES WITH HYDROCHLOROTHIAZIDE IN THE MANAGEMENT OF UNCOMPLICATED, UNTREATED, ESSENTIAL HYPERTENSION. Indian journal of medical sciences, 1964, Volume: 18 Topics: Disease Management; Drug Therapy; Essential Hypertension; Humans; Hydrochlorothiazide; Hypertension	1964
COMPARATIVE EFFICACY OF MEBUTAMATE COMBINED WITH HYDROCHLOROTHIAZIDE IN ESSENTIAL HYPERTENSION. The Journal of the Indiana State Medical Association, 1965, Volume: 58 Topics: Antihypertensive Agents; Carbamates; Drug Therapy; Essential Hypertension; Hydrochlorothiazide; Hype	1965

hydrochlorothiazide and Hypertension, Essential