Clinical trial NCT06339710: Short Benznidazole Regimen for Chronic Phase Chagas Disease Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Chronic Chagas Disease
Keywords: Chagas disease
Short treatment
Benznidazole
Lead sponsor: Evandro Chagas Institute of Clinical Research
Sponsor class: OTHER
Collaborators: name: Andrea Silvestre de Sousa
First posted: 2024-04-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:o Adults aged ≥ 18 years;

* 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.

Primary outcomes:
measure: Proportion of participants with sustained negative Polymerase Chain Reaction (PCR) during the 24 months of follow-up after treatment.
timeFrame: during the 24-month follow-up
Secondary outcomes:
measure: Incidence of Adverse Events (AE) leading to treatment discontinuation during treatment period
timeFrame: during treatment period (up to 8 weeks)
measure: Proportion of participants with positive PCR at different time points
timeFrame: At the different time points: 1, 4, 6, 8, 12, 18 and 24 months after the end of treatment
Other outcomes:
measure: Incidence and severity of clinically relevant events attributed to Chagas disease
timeFrame: during the 24-month follow-up
measure: To measure the quality of life (QoL) of participants
timeFrame: during the 24-month follow-up
measure: To measure the quality of life (QoL) of participants
timeFrame: during the 24-month follow-up
Locations:
city: Minas Gerais
country: Brazil
facility: Israel Molina
state: Belo Horizonte
city: Rio de Janeiro
country: Brazil
facility: Monique Gurgel de Oliveira
state: RJ
Study officials:
References: