Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): study protocol for a multicenter randomized Phase II non-inferiority clinical trial.

BACKGROUND: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. METHODS/DESIGN: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. CONCLUSION: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.

[Tobacco dependency and adolescents: a good time to give up smoking? Relation to social and family factors]. / Tabaquismo y adolescentes: 'buen momento para dejar de fumar? Relación con factores sociofamiliares.

OBJECTIVES: To find the prevalence and dependency of adolescents on tobacco, its relation with family and social factors and the motivation for giving up smoking. DESIGN: Cross-sectional, descriptive study using questionnaires. SETTING: Secondary school, Jaén, Spain. PARTICIPANTS AND MEASUREMENTS: A total of 232 students: the questionnaire included questions on age, sex, tobacco consumption, smoking habits of family and friends, and family structure. The following tests were given: the Apgar family (AFT), Fagerström (FT), and Richmond (RT) tests. RESULTS: Mean age 14.1 years old (95% CI, 13.9-14.3; range, 5 years); 57% boys. A 22% (17.1%-24.5%) were smokers, most of whom were boys (65.2%-86.7%; P<.001, *2) and were older than non-smokers (0.7-1.5; P<.001, Student's t). Mean consumption was 9.2 cigarettes a day (7.4-11.0) over 32 months (14.6-49.5). Friends who smoked were more frequent among adolescents who smoked (80.9%-99%) than among non-smokers (57.3%-70.6%; P<.001, *2). Smoking every day increased consumption by 6 cigarettes a day (3.6-9.2; P<.001, Student's t). In 71% (65.3%-76.6%) of families, there were smokers, principally the parents (63.3%-74.6%), who, in 85% (74.2%-95.8%) of cases, disapproved of their son/daughter smoking. Family dysfunction was more frequent in smokers (30% mild [16.1%-43.9%] and 17% severe [5.4%-28.6%]; P<.001, *2). The FT was positive for 12% (2%-22%) and was associated with the consumption of cigarettes per day (r=0.78; P<.05, Pearson). The RT was positive for 22% (15.1%-28.9%): 70% in the contemplation stage (55.6%-84.3%); 17% in preparation (5.4%-28.6%); 13% in action (3%-23%). CONCLUSIONS: The consumption of tobacco among adolescents is related to family function and having friends who smoke. The low dependency and the motivation to change make this stage of life a good moment to concentrate on anti-smoking counselling.