Shorter Benznidazole Regimens Compared to the Standard Regimen for Chagas Disease

NCT04897516 | Recruiting Phase 3

• 1 other identifier: NuestroBen
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 6

Brief Summary

Chagas disease, a parasitic infection caused by Trypanosoma cruzi, is endemic in much of Latin America and affects people throughout the world. Currently treatment with the only two drugs effective against the infection, benznidazole and nifurtimox, has significant limitations including frequent adverse effects in adult patients. However, timely treatment is key to achieving global objectives of controlling the disease. The standard treatment has a long duration (60 days). NuestroBen will test the hypothesis that shorter treatment regimens of 14 days and 28 days will be non-inferior to the standard 60-day treatment while improving the safety profile.

Conditions

Chagas Disease

Keywords

Chagas disease; Benznidazole; Trypanosoma Cruzi; Standar treatment; Short treatment

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with sustained negativation of parasitemia according to the results of qualitative PCR tests

  Sustained parasitological response will be determined by negative serial qualitative PCR results (two negative PCR results from three DNA extractions from a sample) from the end of treatment with the elimination of sustained parasitaemia until the end of 12 months' follow-up from the end of treatment.

  From the end of treatment, and up to 12 months of follow-up from the end of treatment.

Secondary Outcomes (4)

• Proportion of patients with negative parasitemia at 1, 4, 6 and 8 months follow-up form the end of treatment

  1, 4, 6 and 8 months from the end of treatment

• Incidence and severity of adverse events

  From the end of treatment, and up to 12 months of follow-up from the end of treatment

• Incidence of SAEs, Adverse Events of Special Interest (AESIs) and/or adverse events that cause treatment interruption

  From the end of treatment, and up to 12 months of follow-up from the end of treatment.

• Descriptions of patients adherence to treatment in each study arm.

  2, 4 and 8 weeks

Other Outcomes (2)

• Incidence and severity of adverse events

  From the end of treatment, and up to 12 months of follow-up from the end of treatment.

• Incidence of SAEs, Adverse Events of Special Interest (AESIs) and/or adverse events that cause treatment interruption

  From the end of treatment, and up to 12 months of follow-up from the end of treatment

Study Arms (3)

Short regimen of benznidazole 2 weeks

EXPERIMENTAL

Experimental: Short regimen of benznidazole Participants will receive an investigational treatment of benznidazole for 2 weeks. Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 2 weeks.

Drug: Short regimen of benznidazole

Short regimen of benznidazole 4 weeks

EXPERIMENTAL

Experimental: Short regimen of benznidazole Participants will receive an investigational treatment of benznidazole for 4 weeks. Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 4 weeks.

Drug: Short treatment with benznidazole

Standard treatment with benznidazole

ACTIVE COMPARATOR

Active Comparator: Standard treatment with benznidazole Benznidazole, 300 mg divided into three daily doses (100 mg every 08 hours), orally for 8 weeks

Drug: Standard treatment with benznidazole

Interventions

Short regimen of benznidazole DRUG

Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 2 weeks.

Also known as: Benznidazole 2 weeks

Short regimen of benznidazole 2 weeks

Short treatment with benznidazole DRUG

Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 4 weeks.

Also known as: Benznidazole 4 weeks

Short regimen of benznidazole 4 weeks

Standard treatment with benznidazole DRUG

Benznidazole, 300 mg divided into three daily doses (100 mg every 08 hours), orally for 8 weeks

Also known as: Benznidazole 8 weeks

Standard treatment with benznidazole

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent form;
• Between ≥18 and ≤60 years of age;
• Weight ≥ 50 kg to ≤ 95 kg;
• Confirmation of the diagnosis of T. cruzi infection by conventional serology (a minimum of two tests must be reactive);
• Serial qualitative PCR (one blood sample divided in three DNA extractions, at least one of which must be positive);
• Ability to comply with all exams and specific protocol visits;
• Having a permanent address;
• Normal or minimal structural changes in echocardiogram (left ventricular diastolic diameter (LVDD) \<= 55 mm, diastolic dysfunction, absence of Microaneurysm or tip aneurysm, absence of hypo or generalized akinesia, absence of Systolic dysfunction (low fractional shortening and ejection fraction), and/or absence of mural thrombus);
• Not presenting signs or symptoms of moderate- severe chronic cardiac and/or digestive forms of Chagas disease (criteria detailed in Study Manual and specific SOP);
• No prior history of mental disorders or suicidal tendencies;
• Not suffering from known acute or chronic illnesses at the moment of selection for the study that, in the Investigator's discretion, may interfere with the evaluation of the efficacy or safety of the investigational product (such as acute infections, immunosuppressive conditions, or liver or kidney diseases that have required treatment);
• Not having received a formal indication not to take BZN (contraindication, according to the Summary of Product Characteristics - SmPC);
• No prior history of hypersensitivity, allergy, or serious adverse reactions to any of the nitroimidazole compounds (including BNZ) and/or its components/excipients;
• Have not previously undergone antiparasitic treatment for T. cruzi infection;
• No prior history of drug abuse or alcoholism;

You may not qualify if:

• Subject pregnant or intending to become pregnant during treatment and within 30 days of the last dose of study treatment;
• History of cardiomyopathy, heart failure, or severe ventricular arrhythmia;
• History of digestive surgery potentially related to Chagas Disease or megacolon / mega-esophagus;
• Acute or chronic disease that, in the Investigator's discretion, may interfere with the evaluation of the efficacy or safety of the investigational product (such as acute infection, history of immunosuppressive conditions, or liver or kidney disease that has required treatment);
• Laboratory test values that are considered clinically significant or outside the allowable values, per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1;
• Disease or clinical condition that prevents subjects from consuming oral medication;
• Subjects with a contraindication (known hypersensitivity) to any of the nitroimidazole compounds, e.g. metronidazole;
• Subjects with a history of allergy (serious or not), allergic rash, asthma, intolerance, sensitivity or photosensitivity;
• Concomitant use and/or consumption of allopurinol, antimicrobial and antiparasitic agents, herbal medicines, dietary supplements and energy drinks;
• Scheduled surgery that may interfere with the conduct of the trial and/or with the treatment evaluation;
• Inability to attend study visits, comply with treatment, and cooperate with study procedures;
• Previous participation in a trial for the evaluation of the treatment of T. cruzi infection;
• Simultaneous participation in another trial or within 3 months prior to screening for this trial (in accordance with national regulations).
• Subjects suffering from a serious medical or psychiatric illness that increases the risk associated with study participation or that interferes with the interpretation of study results should not be included.

Sponsors & Collaborators

• Laboratorio Elea Phoenix S.A.: lead
• Drugs for Neglected Diseases: collaborator

Study Sites (6)

Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"

Buenos Aires, C1097, Argentina

NOT YET RECRUITING

Fundación Huésped

Buenos Aires, C1202ABB, Argentina

RECRUITING

Hospital Francisco Javier Muñiz

Buenos Aires, C1282A, Argentina

RECRUITING

Hospital Donación Francisco Santojanni

Buenos Aires, C1408INH, Argentina

NOT YET RECRUITING

Instituto de Cardiología de Corrientes "Juana Francisca Cabral"

Corrientes, W3400, Argentina

RECRUITING

Centro de Chagas y Patología Regional, Hospital Independencia

Santiago del Estero, G4200, Argentina

RECRUITING

Related Publications (1)

• Marques T, Forsyth C, Barreira F, Lombas C, Blum de Oliveira B, Laserna M, Molina I, Bangher MDC, Javier Fernandez R, Lloveras S, Fernandez ML, Scapellato P, Patterson P, Garcia W, Ortiz L, Schijman A, Moreira OC, Garcia L, Viele K, Longhi S, Vaillant M, Tipple C, Fraisse L, Silvestre-Sousa A, Sosa-Estani S, Pinazo MJ. New regimens of benznidazole for the treatment of chronic Chagas disease in adult participants in indeterminate form or with mild cardiac progression (NuestroBen study): protocol for a phase III randomised, multicentre non-inferiority clinical trial. BMJ Open. 2025 Sep 30;15(9):e098079. doi: 10.1136/bmjopen-2024-098079.

  PMID: 41027700 DERIVED

MeSH Terms

Conditions

Chagas Disease

Interventions

benzonidazole

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Study Officials

• María Jesús Pinazo, MD

  Drugs for Neglected Diseases

  STUDY DIRECTOR

Central Study Contacts

Carola Lombas, MD

CONTACT

(54) 11 44898300; carola.lombas@elea.com

Tayná Marques, MSc

CONTACT

(55) 21 9978 40503; tmarques@dndi.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase III, open-label, prospective, controlled, multicenter, non-inferiority study to compare the efficacy of the Drug: 1. Short regimen of benznidazole :Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 2 weeks. 2\. Drug: Short regimen of benznidazole : Benznidazole, under the brand name Abarax (100 mg tablet), 300 mg divided into three daily doses (100 mg every 08 hours) for 4 weeks. And 3. Drug: Standard treatment with benznidazole : Benznidazole, 300 mg divided into three daily doses (100 mg every 08 hours), orally for 8 weeks

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: May 21, 2021
• Study Start: July 28, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 30, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 6 months after publication of study results
• Access Criteria: Beginning 6 months after publication of study results

Locations

AR (6)