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
D. Molina-Morant,
M. L. Fernández,
P. Bosch-Nicolau,
E. Sulleiro,
M. Bangher,
F. Salvador,
A. Sanchez-Montalva,
A. L. P. Ribeiro,
A. M. B. de Paula,
S. Eloi,
R. Correa-Oliveira,
J. C. Villar,
S. Sosa-Estani,
I. Molina
Affiliations
D. Molina-Morant
Infectious Diseases Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona
M. L. Fernández
Departamento de Clínica, Patología y Tratamiento, Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, Ministerio de Salud y Desarrollo Social
P. Bosch-Nicolau
Infectious Diseases Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona
E. Sulleiro
Microbiology Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona
M. Bangher
Instituto de Cardiología de Corrientes Juana Francisca Cabral (Argentina)
F. Salvador
Infectious Diseases Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona
A. Sanchez-Montalva
Infectious Diseases Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona
A. L. P. Ribeiro
Programa de Pós-graduação Infectologia e Medicina Tropical, Faculdade de Medicina da Universidade Federal de Minas Gerais
A. M. B. de Paula
Laboratory of Health Science, Postgraduate Program in Health Sciences, Universidade Estadual de Montes Claros (Unimontes)
S. Eloi
Programa de Pós-graduação em Patologia, Departamento de Propedêutica Complementar, Faculdade de Medicina da Universidade Federal de Minas Gerais
R. Correa-Oliveira
René Rachou Institute, Oswaldo Cruz Foundation
J. C. Villar
Faculty of Health Sciences, Universidad Autónoma de Bucaramanga and Research Department
S. Sosa-Estani
Chagas Clinical Program, Drugs for Neglected Disease initiative (DNDi)
I. Molina
Infectious Diseases Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona
Abstract 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.
