Short-course Benznidazole Treatment to Reduce Trypanosoma Cruzi Parasitic Load in Women of Reproductive Age

NCT03672487 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: R01HD095857
• Study Type: interventional
• Target: 87
• Locations: 2 countries
• Sites: 3

Brief Summary

The investigators are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short 30-day treatment with BZN 150mg/day (30d/150mg) vs. a 60-day treatment with BZN 300 mg/day (60d/300mg). The investigators will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at six months postpartum, and follow them up with the following specific aims: Specific Aim 1: To measure the effect of BZN 30d/150mg compared to 60d/300mg preconceptional treatment on parasitic load measured by the frequency of positive PCR (primary outcome) and by real-time quantitative PCR (qPCR), immediately (Specific Aim 1a) and 10 months (Specific Aim 1b) after treatment. Hypothesis 1a: The frequency of positive PCR and the parasitic load measured by qPCR immediately after BZN 30d/150mg will be non-inferior (Non Inferiority \[NI\] margin for PCR: 10% absolute difference) to BZN 60d/300mg. Hypothesis 1b: The frequency of positive PCR and the parasitic load measured by qPCR 10 months after BZN 30d/150mg will be non-inferior (NI margin for PCR: 9% absolute difference) to BZN 60d/300mg. Specific Aim 2: To measure the frequency of serious adverse events leading to treatment interruption of BZN 30d/150mg compared to 60d/300mg. Hypothesis 2: The frequency of serious adverse events leading to treatment interruption will be 50% lower with BZN 30d/150mg than with BZN 60d/300mg. A 24-month recruitment period is planned in four hospitals with 23,436 deliveries in 2015 and frequencies of T. cruzi seropositive women varying from 1.5% to 4.8%. The investigators are planning to enroll 600 T. cruzi seropositive women.

Conditions

Chagas Disease

Keywords

Congenital Transmission; Trypanosoma cruzi; Benznidazole

Outcome Measures

Primary Outcomes (2)

• Global PCR (Conventional PCR and Real-time Quantitative PCR) Immediately After the End of Treatment.

  Number of participants with at least one of the four conventional and/or one of the four quantitative PCR tests positive.

  Immediately after the end of treatment: 30 days for the 30-day arm, and 60 days for the 60-day arm.

• Global PCR (Conventional PCR and Real-time Quantitative PCR) at 10 Months After the End of the 60-day Treatment Period.

  Number of participants with at least one of the four conventional and/or one of the four quantitative PCR tests positive.

  10 months after the end of the 60-day treatment period.

Secondary Outcomes (3)

• Serious Adverse Events and/or Any Adverse Event Leading to Treatment Discontinuation.

  Randomization until last visit (10 months after the end of treatment or early termination).

• Median Parasitic Load by qPCR Immediately After the End of Treatment in Detectable Samples.

  Immediately after the end of treatment.

• Median Parasitic Load by qPCR at 10 Months From the End of the 60-day Treatment Period in Detectable Samples

  10 months from the end of the 60-day treatment period.

Study Arms (2)

60/300mg

ACTIVE COMPARATOR

The investigators will use a preparation of benznidazole (BZN) that is commercially available in Argentina: Abarax® 100mg and 50mg tablets from ELEA laboratories (Buenos Aires, Argentina). The investigators will purchase the drug at full cost. Interventions: The standard 60d course will be 300 mg per day, which is similar to the dose used in the second phase of the BENEFIT trial. The drug will be administered orally in two doses per day: the standard course will be one 100mg and one 50mg tablet in the morning and in the evening for 60 days.

Drug: Benznidazole

30/150mg

EXPERIMENTAL

The investigators will use a preparation of benznidazole (BZN) that is commercially available in Argentina: Abarax® 100mg and 50mg tablets from ELEA laboratories (Buenos Aires, Argentina). ELEA laboratories will prepare the placebo oral tablets, which will be identical to the drug tablets in aspect and taste. The investigators will purchase the drug and placebo at full cost. Interventions: The BZN short course low dose scheme will be 150 mg per day for 30 days. The drug will be administered orally in two doses per day: the short course treatment will start with the active drug and then placebo oral tablet; one 100 mg tablet and one placebo tablet in the morning and one 50 mg tablet and one placebo tablet in the evening for the first 30 days. The last 30 days will be two placebo tablets in the morning and the evening.

Drug: Benznidazole; Drug: Placebo Oral Tablet

Interventions

Benznidazole DRUG

Benznidazole tablet

Also known as: Abarax

30/150mg; 60/300mg

Placebo Oral Tablet DRUG

Sugar pill manufactured to mimic Benznidazole

Also known as: Placebo (for Benznidazole)

30/150mg

Eligibility Criteria

• Age: 13 Years+
• Gender Eligibility Details: Women of childbearing age
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent from the mother.
• T. cruzi seropositivity confirmed by at least two positive tests.
• Live birth.

You may not qualify if:

• Women residing outside of the provinces of Chaco, Santiago del Estero, or Tucumán.
• Previous trypanocide treatment (BZN or nifurtimox).
• Female sterilization; no intention to use modern contraception methods during treatment.
• Positive pregnancy test.
• History of severe alcohol abuse within two years; renal insufficiency.

Sponsors & Collaborators

• Institute for Clinical Effectiveness and Health Policy: collaborator
• Tulane University School of Public Health and Tropical Medicine: lead
• University of California, San Diego: collaborator

Study Sites (3)

University of California at San Diego

San Diego, California, 92093, United States

Location

Tulane School of Public Health and Tropical Medicine

New Orleans, Louisiana, 70112, United States

Location

Institute for Clinical Effectiveness and Health Policy

Buenos Aires, Argentina

Location

Related Publications (1)

• Cafferata ML, Toscani MA, Althabe F, Belizan JM, Bergel E, Berrueta M, Capparelli EV, Ciganda A, Danesi E, Dumonteil E, Gibbons L, Gulayin PE, Herrera C, Momper JD, Rossi S, Shaffer JG, Schijman AG, Sosa-Estani S, Stella CB, Klein K, Buekens P. Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): a non-inferiority randomized controlled trial study protocol. Reprod Health. 2020 Aug 24;17(1):128. doi: 10.1186/s12978-020-00972-1.

  PMID: 32831069 DERIVED

MeSH Terms

Conditions

Chagas Disease

Interventions

benzonidazole

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Pierre Buekens
• Organization: Tulane University Weatherhead School of Public Health

pbuekens@tulane.edu

504-988-8803

Study Officials

• Pierre Buekens, MD, PhD

  Tulane University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2018
• First Posted: September 14, 2018
• Study Start: June 1, 2019
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2025
• Last Updated: April 9, 2026
• Results First Posted: April 9, 2026

Record last verified: 2026-02

Locations

US (2); AR (1)