Double Blind, Phase III Randomized,Safety and Efficacy Non-inferiority Trial to Evaluate Two Short Benznidazole Regimens for the Treatment of Adults in the Chronic Phase of Chagas Disease in Its Indeterminate and Mild Cardiac Forms in Bolivia and Colombia
Double Blind, Phase III Randomized,Safety and Efficacy Non-inferiority Trial to Evaluate Two Short Benznidazole Regimens for the Treatment of Adults in the Chronic Phase of Chagas Disease in Its Indeterminate and Mild Cardiac Forms in Bolivia and Colombia
Multicentric study on Chagas disease that seeks to evaluate a new treatment regimen using the drug benznidazole. Currently, existing treatment regimens are long and have frequent side effects, which leads to a high dropout rate among patients. The research proposes testing two shorter benznidazole regimens to see if they are as effective as standard treatment, but with fewer side effects.
The study will have 672 participants and will be carried out in four locations, Bolivia and Colombia. The objective is to analyze the efficacy and safety of new treatment regimens, evaluating the parasitological response in comparison with standard treatment. In addition, an economic assessment will be carried out to analyze direct and indirect costs, including procedures associated with the management of adverse events.
Chagas disease is a major cause of heart disease, morbidity, and premature loss of life in the Americas. Eliminating the Trypanosoma cruzi parasite using antitrypanosomal drugs has shown to produce cure in children, halt future congenital transmission, and reduce morbidity from the disease. However, the current treatment regimens are lengthy (60 days) and entail frequent side effects, causing about 20% of patients to drop out of treatment, and discouraging others from starting. Recent research found that a reduced treatment of benznidazole still has adequate efficacy with few side effects.
In this international, multicenter, double-blind, phase III, placebo-controlled study, 672 participants will be randomly assigned to receive the standard-dose of benznidazole (300 mg daily for 8 weeks) or the short experimental regimens (benznidazole 300 mg daily for the first 2 weeks plus placebo for the last 6 weeks or benznidazole 300 mg daily for the first 4 weeks plus placebo for the last 4 weeks). Efficacy will be assessed considering a non-inferiority design and through the detection of parasite deoxyribonucleic acid (DNA) through molecular biology (Polymerase Chain Reaction - PCR). Meanwhile, safety will be evaluated through a superiority design, with the aim to find the new regimen as effective as the standard one, but superior in terms of safety. An intention-to-treat analysis will be performed, and statistical significance will be set at 0.025 for the non-inferiority outcome (positive PCR) and 0.05 for the superiority outcome.
The study population will be adult participants, 18 years or older, with chronic Chagas disease in its indeterminate or mild cardiac forms, with a positive diagnosis from two serological assays. The trial will be conducted in four sites: two in Bolivia, and two in Colombia. The primary endpoint will be parasitological response determined as sustained negative qualitative PCR at 24 months after treatment. The proportion of participants with positive qualitative PCR will be measured at 1, 4, 6, 8, 12, 18, and 24 months from end of treatment. The frequency of adverse events leading to treatment discontinuation will be compared. An economic evaluation will be conducted assessing the direct and indirect costs, including procedures associated with the management of adverse events.
Inclusion Criteria:o Adults aged ≥ 18 years;
Exclusion Criteria:
o Currently pregnant, breastfeeding or expressing gestational desire for the next 2 months.