Clinical trial NCT03672487: Short-course Benznidazole Treatment to Reduce Trypanosoma Cruzi Parasitic Load in Women of Reproductive Age
Official title: Short-course Benznidazole Treatment to Reduce Trypanosoma Cruzi Parasitic Load in Women of Reproductive Age: A Non-inferiority Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chagas Disease
Keywords: Congenital Transmission
Trypanosoma cruzi
Benznidazole
Lead sponsor: Tulane University
Sponsor class: OTHER
Collaborators: name: Institute for Clinical Effectiveness and Health Policy
name: University of California, San Diego
First posted: 2018-09-14
Enrollment: 273
Sex: FEMALE
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Frequency of positive PCR and the parasitic load measured by qPCR immediately after BZN 30d/150mg
timeFrame: 30 days for the 30d course arm, and 60 days for the 60d course arm
measure: The frequency of positive PCR and the parasitic load measured by qPCR 10 months after BZN 30d/150mg
timeFrame: 10 months from the end of the 60d treatment
Secondary outcomes:
measure: The frequency of serious adverse events leading to treatment interruption of BZN 30d/150mg compared to 60d/300mg immediately after BZN 30d/150mg
timeFrame: 60 days after treatment initiation
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: New Orleans
country: United States
facility: Tulane School of Public Health and Tropical Medicine
state: Louisiana
city: Buenos Aires
country: Argentina
facility: Institute for Clinical Effectiveness and Health Policy
Study officials:
affiliation: Tulane University
name: Pierre Buekens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.