Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): a non-inferiority randomized controlled trial study protocol

María L Cafferata, María A Toscani, Fernando Althabe, Jose M Belizán, Eduardo Bergel, Mabel Berrueta, Edmund V Capparelli, Álvaro Ciganda, Emmaria Danesi, Eric Dumonteil, Luz Gibbons, Pablo E Gulayin, Claudia Herrera, Jeremiah D Momper, Steven Rossi, Jeffrey G Shaffer, Alejandro G Schijman, Sergio Sosa-Estani, Candela B Stella, Karen Klein, Pierre Buekens, María L Cafferata, María A Toscani, Fernando Althabe, Jose M Belizán, Eduardo Bergel, Mabel Berrueta, Edmund V Capparelli, Álvaro Ciganda, Emmaria Danesi, Eric Dumonteil, Luz Gibbons, Pablo E Gulayin, Claudia Herrera, Jeremiah D Momper, Steven Rossi, Jeffrey G Shaffer, Alejandro G Schijman, Sergio Sosa-Estani, Candela B Stella, Karen Klein, Pierre Buekens

Abstract

Background: Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for preconceptional treatment to reduce parasitic load. The fear of treatment-related side effects limits the implementation of the Argentine guideline recommending BZN 60d/300 mg (or equivalent) treatment of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60d/300 mg course is not yet established. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed.

Methods and design: We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150 mg/day (30d/150 mg) vs. BZN 60d/300 mg. We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at 6 months postpartum, and follow them up with the following specific aims: Specific aim 1: to measure the effect of BZN 30d/150 mg compared to 60d/300 mg preconceptional treatment on parasitic load measured by the frequency of positive Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately and 10 months after treatment. Specific aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment interruption.

Trial registration: ClinicalTrials.gov . Identifier: NCT03672487 . Registered 14 September 2018.

Keywords: Benznidazole; Chagas disease; Preconception care; Randomized controlled trial; Trypanosoma cruzi.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

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Fig. 1
Study design

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