tribendimidine and Drug-Related-Side-Effects-and-Adverse-Reactions

Praziquantel is the only option for treatment of the liver fluke infection Opisthorchis viverrini. Tribendimidine could be an alternative drug. We aimed to assess the efficacy and safety of a single, oral dose of tribendimidine, compared with praziquantel administered in two doses, in participants with O viverrini infection.. We did an open-label, randomised, non-inferiority, phase 2 trial in children (8-14 years) and adolescents and adults (≥15 years) in Champasack province, southern Laos. Participants infected with O viverrini were randomly assigned (1:1), via a computer-generated block-randomisation procedure (block sizes of two, four, and six), to receive a single, oral dose of tribendimidine (200 mg for children, 400 mg for adolescents and adults) or two oral doses of praziquantel (50 mg/kg bodyweight and 25 mg/kg bodyweight, 6 h apart). Physicians assessing adverse events and laboratory personnel were masked to treatment allocation, but the investigators administering treatment and the participants could have recognised the treatment group based on differences in the number, appearance, and odour of the tablets. The primary outcomes were cure rate, defined as no parasite eggs in stool at 3 weeks' follow-up, and egg reduction rate. We did available-case analysis of all participants with primary endpoint data. The non-inferiority margin for the difference in cure rates between the groups was pre-specified as -3 percentage points. Adverse events were monitored at 3 h and 24 h after treatment. This trial is registered, number ISRCTN96948551.. Between Feb 1, and April 30, 2014, we assigned 607 participants with confirmed O viverrini infection to receive tribendimidine (n=300) or praziquantel (n=307). 11 participants (five in the tribendimidine group and six in the praziquantel group) did not provide stool samples at 3 weeks' follow-up and were excluded from the available-case analysis. 276 (93·6%) of 295 participants in the tribendimidine group were cured compared with 293 (97·3%) of 301 participants in the praziquantel group. The difference in cure rates between the two groups was -3·8 percentage points (95% CI -7·1 to -0·4), thus the lower limit of the confidence interval exceeded the non-inferiority margin. In both treatment groups, egg reduction rates were 99·9%. Adverse events were of mild and moderate intensity and were more frequent in the praziquantel group than in the tribendimidine group (odds ratio 4·5, 95% CI 3·2-6·3; p<0·0001). The most frequent adverse events were headache, vertigo, nausea, and fatigue.. Tribendimidine has a slightly lower cure rate than praziquantel and non-inferiority was not shown. However, tribendimidine has a similar egg reduction rate to praziquantel and leads to fewer adverse events and thus might complement praziquantel in O viverrini control programmes, particularly in settings co-endemic for hookworm.. Joint Global Health Trials scheme from the Wellcome Trust, Department for International Development, and Medical Research Council.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Anthelmintics; Child; Drug-Related Side Effects and Adverse Reactions; Feces; Female; Humans; Laos; Male; Middle Aged; Opisthorchiasis; Opisthorchis; Parasite Egg Count; Phenylenediamines; Praziquantel; Treatment Outcome; Young Adult

Clonorchiasis is of considerable public health importance, particularly in the People's Republic of China (PR China), where most of the 15 million individuals infected with Clonorchis sinensis are currently concentrated. Praziquantel is the drug of choice, but tribendimidine might be an alternative.. We performed a randomized open-label trial in Guangxi, PR China, to assess the efficacy and safety of 400 mg tribendimidine once, 400 mg tribendimidine daily for 3 days, and 75 mg/kg praziquantel in 1 day divided in 3 doses against parasitological-confirmed C. sinensis infections. Cure and egg reduction rates were determined 3 weeks posttreatment using available case analysis. Clinical symptoms were documented at baseline, and adverse events were recorded and graded 3 and 24 hours after each dose.. A total of 74 patients were included in the final analysis. Single-dose tribendimidine achieved a cure rate of 44%, whereas cure rates of 58% and 56% were obtained for tribendimidine administered for 3 days and praziquantel, respectively. High egg reduction rates (97.6%-98.8%) were observed for all treatment regimens. Single-dose tribendimidine was the best-tolerated treatment scheme. Patients treated with praziquantel experienced significantly more adverse events than did tribendimidine recipients (P < .05).. Tribendimidine has an efficacy comparable to praziquantel in the treatment of C. sinensis infection and resulted in fewer adverse events compared to praziquantel. Larger clinical trials are warranted among C. sinensis-infected patients to determine the potential of tribendimidine against clonorchiasis and other helminthiases. Clinical Trials Registration.Controlled-Trials.com, ISRCTN80829842.

Topics: Adult; Animals; Anthelmintics; China; Clonorchiasis; Clonorchis sinensis; Drug-Related Side Effects and Adverse Reactions; Feces; Female; Humans; Male; Middle Aged; Parasite Egg Count; Phenylenediamines; Praziquantel; Treatment Outcome