Page last updated: 2024-10-29

isoniazid and Premature Birth

isoniazid has been researched along with Premature Birth in 2 studies

Hydra: A genus of freshwater polyps in the family Hydridae, order Hydroida, class HYDROZOA. They are of special interest because of their complex organization and because their adult organization corresponds roughly to the gastrula of higher animals.
hydrazide : Compounds derived from oxoacids RkE(=O)l(OH)m (l =/= 0) by replacing -OH by -NRNR2 (R groups are commonly H). (IUPAC).

Premature Birth: CHILDBIRTH before 37 weeks of PREGNANCY (259 days from the first day of the mother's last menstrual period, or 245 days after FERTILIZATION).

Research Excerpts

Excerpt	Relevance	Reference
"In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group)."	5.30	Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women. ( Aaron, L; Aurpibul, L; Bhosale, R; Bradford, S; Chakhtoura, N; Chipato, T; Costello, D; Gupta, A; Hesseling, A; Jean-Philippe, P; Masheto, GR; Mave, V; McCarthy, K; Mmbaga, BT; Montepiedra, G; Onyango-Makumbi, C; Rouzier, V; Shin, K; Sterling, TR; Stranix-Chibanda, L; Theron, G; Vhembo, T; Violari, A; Weinberg, A; Zimmer, B, 2019)

Research

Studies (2)

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	1 (50.00)	24.3611
2020's	1 (50.00)	2.80

Authors

Authors	Studies
Quincer, EM	1
Lyland, A	1
Onyango, D	1
LaCourse, SM	1
Figueroa, J	1
John-Stewart, GC	1
Cranmer, LM	1
Gupta, A	1
Montepiedra, G	1
Aaron, L	1
Theron, G	1
McCarthy, K	1
Bradford, S	1
Chipato, T	1
Vhembo, T	1
Stranix-Chibanda, L	1
Onyango-Makumbi, C	1
Masheto, GR	1
Violari, A	1
Mmbaga, BT	1
Aurpibul, L	1
Bhosale, R	1
Mave, V	1
Rouzier, V	1
Hesseling, A	1
Shin, K	1
Zimmer, B	1
Costello, D	1
Sterling, TR	1
Chakhtoura, N	1
Jean-Philippe, P	1
Weinberg, A	1

Clinical Trials (2)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase IV Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Safety of Immediate (Antepartum-Initiated) Versus Deferred (Postpartum-Initiated) Isoniazid Preventive Therapy Among HIV-Infected Women in High Tuberculosis (TB) Incidence Setting[NCT01494038]	Phase 4	956 participants (Actual)	Interventional	2014-08-19	Completed
TB Screening Improves Preventive Therapy Uptake Trial[NCT04557176]		1,719 participants (Actual)	Interventional	2020-11-16	Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Incidence Rate of Combined Endpoint, Antepartum: Grade 3 or Higher AE Related to Treatment, or Discontinuation of Treatment Due to AE

Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata (NCT01494038)
Timeframe: Measured from study entry through end of pregnancy

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	15.93
Arm B (Deferred INH Treatment)	13.79

Incidence Rate of Combined Endpoint, up to 12 Weeks Postpartum: Grade 3 or Higher AE Related to Treatment, or Discontinuation of Treatment Due to AE

Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through 12 weeks after birth

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	16.98
Arm B (Deferred INH Treatment)	10.09

Incidence Rate of Combined Endpoint: Grade 3 or Higher Adverse Events (AEs) Related to Treatment, or AE Causing Discontinuation of Treatment

Incidence rate, calculated by Mantel-Haenszel (MH), weighted by gestational age strata 1) gestational age at entry less than 24 weeks or 2) gestational age at entry greater than or equal to 24 weeks. AE's include laboratory results, signs/symptoms, or diagnoses; graded as per Division of AIDS (DAIDS) or by protocol-defined hepatotoxicity measures. Related to treatment indicates possibly, probably, or definitely related to INH or Placebo for INH as judged by Independent Endpoint Review Committee. Discontinuation refers to permanent discontinuation of study treatment. (NCT01494038)
Timeframe: Measured from study entry through Week 48 after birth

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	15.03
Arm B (Deferred INH Treatment)	14.93

Incidence Rate of Combined Endpoints: Infant TB or Infant Death

Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through Week 48 after birth

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	2.99
Arm B (Deferred INH Treatment)	4.68

Incidence Rate of Combined Endpoints: Maternal TB or Maternal Death

Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through Week 48 after birth

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	1.00
Arm B (Deferred INH Treatment)	1.38

Incidence Rate of Combined Endpoints: Maternal TB, Maternal Death, Infant TB, or Infant Death

Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through Week 48 after birth

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	3.42
Arm B (Deferred INH Treatment)	4.72

Incidence Rate of Infant Death

Incidence rate was calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through Week 48 after birth

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	2.99
Arm B (Deferred INH Treatment)	4.42

Incidence Rate of Maternal Deaths

Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through Week 48 postpartum

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	0.40
Arm B (Deferred INH Treatment)	0.78

Incidence Rate of TB Infection Among Mothers

Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Probable or confirmed TB infection, as judged by Secondary Endpoint Review Committee (NCT01494038)
Timeframe: Measured from study entry to Week 48 after birth

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	0.60
Arm B (Deferred INH Treatment)	0.59

Incidence Rate of Tuberculosis (TB) Among Infants

Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Probable or confirmed TB, or congenital TB as defined using the Cantwell criteria (see reference), judged by the Secondary Endpoint Review Committee. Includes an infant death due to unknown cause. (NCT01494038)
Timeframe: Measured from study entry through Week 48 after birth

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	0.54
Arm B (Deferred INH Treatment)	0.52

Incidence Rate, Antepartum, of Grade 3 or Higher AE

Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through end of pregnancy

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	56.36
Arm B (Deferred INH Treatment)	50.88

Incidence Rate, Antepartum, of Hepatotoxicity, Defined by DAIDS, Any Cause

Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through delivery

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	1.77
Arm B (Deferred INH Treatment)	2.59

Incidence Rate, Antepartum, of Hepatotoxicity, Defined by DAIDS, Related to Treatment

Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Hepatotoxicity definition as defined by DAIDS AE grading criteria 1.0. (NCT01494038)
Timeframe: Measured from study entry through delivery

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	1.77
Arm B (Deferred INH Treatment)	2.59

Incidence Rate, Antepartum, of Hepatotoxicity, Defined by Protocol-specific Definition of Hepatotoxicity, Related to Treatment

Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata. Protocol-specific definition of hepatotoxicity: Any one of the following: 1) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 times the upper limit of normal (ULN), where ULN is specified by the clinic physician; 2) Total bilirubin > 3 X ULN; 3) ALT greater than 3 X ULN and total bilirubin greater than 2 X ULN; or 4) ALT > 3 X ULN and persistent symptomatic clinical hepatitis (NCT01494038)
Timeframe: Measured from study entry through delivery

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	1.77
Arm B (Deferred INH Treatment)	2.59

Incidence Rate, Antepartum, of Hepatotoxicity, Protocol-specific Definition, Any Cause

Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through delivery

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	1.77
Arm B (Deferred INH Treatment)	2.59

Incidence Rate, to 12 Weeks Postpartum, of Hepatotoxicity, Protocol-specific Definition, Any Cause

Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through 12 weeks postpartum

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	8.37
Arm B (Deferred INH Treatment)	4.98

Incidence Rate, to 12 Weeks Postpartum, of Hepatotoxicity, Protocol-specific Definition, Related to Treatment

Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata (NCT01494038)
Timeframe: Measured from study entry through 12 weeks postpartum

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	7.91
Arm B (Deferred INH Treatment)	4.52

Incidence Rate, up to 12 Weeks Postpartum, of Grade 3 or Higher AE

Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study entry through 12 weeks postpartum

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	56.48
Arm B (Deferred INH Treatment)	40.59

Incidence Rate, up to 12 Weeks Postpartum, of Hepatotoxicity, Defined by DAIDS, Any Cause

Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. (NCT01494038)
Timeframe: Measured from study start through 12 weeks postpartum

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	8.37
Arm B (Deferred INH Treatment)	4.98

Incidence Rate, up to 12 Weeks Postpartum, of Hepatotoxicity, Defined by DAIDS, Related to Treatment

Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata (NCT01494038)
Timeframe: Measured from study start through 12 weeks postpartum

Intervention	events per 100 person-years (Number)
Arm A (Immediate INH Treatment)	7.91
Arm B (Deferred INH Treatment)	4.52

Number of Infants Hospitalized

Hospitalization due to reasons other than birth (NCT01494038)
Timeframe: Measured from study entry through Week 48 after birth

Intervention	Participants (Count of Participants)
Arm A (Immediate INH Treatment)	73
Arm B (Deferred INH Treatment)	75

Number of Infants With Grade 3 or Higher Clinical or Laboratory AE

Laboratory, sign/symptom, or diagnoses graded as 3 or higher by DAIDS criteria. (NCT01494038)
Timeframe: Measured from study entry through Week 48 after birth

Intervention	Participants (Count of Participants)
Arm A (Immediate INH Treatment)	193
Arm B (Deferred INH Treatment)	196

Number of Infants With Grade 3 or Higher Clinical or Laboratory AE Related to Treatment

As before, but AE is judged to be possibly, probably, or definitely related to INH or Placebo for INH, by clinic medical staff (NCT01494038)
Timeframe: Measured from study entry through Week 48 after birth

Intervention	Participants (Count of Participants)
Arm A (Immediate INH Treatment)	5
Arm B (Deferred INH Treatment)	6

Number of Mothers With a Fetal Death

Fetal deaths include both stillbirths and spontaneous abortions; in case of a multiple birth, mothers who had at least one fetal death (NCT01494038)
Timeframe: Measured from study entry through end of pregnancy

Intervention	Participants (Count of Participants)
Arm A (Immediate INH Treatment)	17
Arm B (Deferred INH Treatment)	9

Number of Mothers With an Infant Born Prematurely

Premature birth is defined as gestational age of < 37 weeks at delivery. (NCT01494038)
Timeframe: Measured at delivery

Intervention	Participants (Count of Participants)
Arm A (Immediate INH Treatment)	48
Arm B (Deferred INH Treatment)	40

Number of Mothers With Tuberculosis Resistant to INH

Resistance to INH from isolates of Mycobacterium tuberculosis, as a percentage of mothers who develop culture-confirmed TB (NCT01494038)
Timeframe: Measured from study entry through Week 48 postpartum

Intervention	Participants (Count of Participants)
Arm A (Immediate INH Treatment)	1
Arm B (Deferred INH Treatment)	0

Pharmacokinetic (PK) Parameter: Adjusted Mean of Area Under the Curve (AUC24h), for EFV

Pharmacokinetic parameter was estimated from population PK modeling fitted to the intensive PK data. AUC0-24h was predicted using population pharmacokinetic model using the NONMEM software program. A 2-compartment model with first-order absorption with transit compartment and first-order elimination with well-stirred liver model to capture hepatic clearance and first-pass extraction with 1 parameter (hepatic intrinsic clearance) was used, (NCT01494038)
Timeframe: Measured at antepartum (third trimester and >= 2 weeks after starting study drug) and week 16 postpartum (+/-) 4 weeks) while on active INH; blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dosing.

Intervention	hour*mg/L (Mean)
	Third trimester of pregnancy	Week 16 postpartum
Fast Metabolizers	38.5	46.9
Intermediate Metabolizers	62.5	76.2
Slow Metabolizers	153.02	186

Pharmacokinetic (PK) Parameter: Adjusted Mean of Area Under the Curve of Plasma Concentration Versus Time (AUC24h), for INH

Intervention	hour*mg/L (Mean)
	Third trimester of pregnancy	Week 16 postpartum
Fast Metabolizers	3.63	4.25
Intermediate Metabolizers	6.55	7.67
Slow Metabolizers	21.6	25.3

Trials

1 trial available for isoniazid and Premature Birth

Article	Year
Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women. The New England journal of medicine, 2019, 10-03, Volume: 381, Issue:14 Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Double-Blind Method	2019
Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women. The New England journal of medicine, 2019, 10-03, Volume: 381, Issue:14 Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Double-Blind Method	2019
Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women. The New England journal of medicine, 2019, 10-03, Volume: 381, Issue:14 Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Double-Blind Method	2019
Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women. The New England journal of medicine, 2019, 10-03, Volume: 381, Issue:14 Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Double-Blind Method	2019

Other Studies

1 other study available for isoniazid and Premature Birth

Article	Year
The effect of antenatal isoniazid preventive therapy on birth outcomes in Western Kenya. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2023, Dec-01, Volume: 27, Issue:12 Topics: Female; HIV Infections; Humans; Infant, Newborn; Isoniazid; Kenya; Perinatal Death; Pregnancy; Prema	2023