Short Benznidazole Regimen for Chronic Phase Chagas Disease Patients

NCT ID: NCT06339710

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-30
• Study Completion Date: 2026-10-30

Brief Summary

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.

Detailed Description

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.

Conditions

Chronic Chagas Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Short treatment 1

benznidazole 300 mg daily for the first 2 weeks plus placebo for the last 6 weeks or

Group Type: EXPERIMENTAL

benznidazole 300 mg daily 8 weeks

Intervention Type: DRUG

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)

Short Treatment 2

benznidazole 300 mg daily for the first 4 weeks plus placebo for the last 4 weeks

Group Type: EXPERIMENTAL

benznidazole 300 mg daily 8 weeks

Intervention Type: DRUG

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)

Standard treatment

benznidazole 300 mg daily for 8 weeks

Group Type: ACTIVE_COMPARATOR

benznidazole 300 mg daily 8 weeks

Intervention Type: DRUG

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)

Interventions

benznidazole 300 mg daily 8 weeks

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)

Intervention Type: DRUG

Other Intervention Names

benznidazole 300 mg daily for the first 2 weeks plus placebo for the last 6 weeks; benznidazole 300 mg daily for the first 4 weeks plus placebo for the last 4 weeks

Eligibility Criteria

Inclusion Criteria

• CD diagnosis through the positivity of two serological tests that use different antigens (recombinant and native antigens, according to World Health Organization (WHO) recommendations) (28).
• Informed consent form read and signed by the participant.
• Weight ≥ 50 kg to ≤ 95 kg.

Exclusion Criteria

• o Currently pregnant, breastfeeding or expressing gestational desire for the next 2 months.

• Previously received treatment with Benznidazole (BZN) or NIfurtimox (NFX) - (either completely or incompletely);
• Any concomitant use or documented history of using allopurinol or antifungals (ketoconazole, itraconazole and posaconazole);
• History of hypersensitivity, allergic or serious adverse event (SAE) to any "nitroimidazole", and/or its components;
• Acute or chronic health problems that, in the informed opinion of the investigator, may interfere with the evaluation of the efficacy and/or safety of the drug. Examples are acute infections, Human Immunodeficiency Virus (HIV) infections, liver disease with liver failure and kidney disease requiring support treatment;
• Signs and/or symptoms of severe cardiac form of CD ;
• History of cardiomyopathy, heart failure or severe ventricular arrhythmia of any etiology;
• Alcoholic participants or those with a history of alcohol abuse (considered as intake of >4 drinks on any single day AND >14 drinks per week for men and >3 drinks on any single day AND >7 drinks per week for women);
• Have basic laboratory parameters outside the normal range or parameters that are considered clinically relevant by the physician responsible for the participant;
• Participation in another clinical trial over the past 12 months.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Andrea Silvestre de Sousa

UNKNOWN

Sponsor Role: collaborator

Evandro Chagas Institute of Clinical Research

OTHER

Sponsor Role: lead

Responsible Party

Israel Molina

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Israel Molina

Minas Gerais, Belo Horizonte, Brazil

Monique Gurgel de Oliveira

Rio de Janeiro, Rio de Janeiro, Brazil

Countries

Brazil

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

U1111-1288-5508

Identifier Type: -

Identifier Source: org_study_id