Chagas Disease
Conditions
Keywords
Congenital Transmission, Trypanosoma cruzi, Benznidazole
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.
Interventions
DRUGBenznidazole
Benznidazole tablet
DRUGPlacebo Oral Tablet
Sugar pill manufactured to mimic Benznidazole
Sponsors
Tulane University School of Public Health and Tropical Medicine
Institute for Clinical Effectiveness and Health Policy
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Placebo
Eligibility
Sex/Gender
FEMALE
Age
13 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global PCR (Conventional PCR and Real-time Quantitative PCR) Immediately After the End of Treatment. | Immediately after the end of treatment: 30 days for the 30-day arm, and 60 days for the 60-day arm. | Number of participants with at least one of the four conventional and/or one of the four quantitative PCR tests positive. |
| Global PCR (Conventional PCR and Real-time Quantitative PCR) at 10 Months After the End of the 60-day Treatment Period. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Parasitic equivalents/mL. |
| 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. | Parasitic equivalents/mL. |
Countries
Argentina, United States
Contacts
PRINCIPAL_INVESTIGATORPierre Buekens, MD, PhD
Tulane University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 8 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants |
| Age, Continuous | 29.6 years |
| Endemic Area Endemic | 26 Participants |
| Endemic Area Non-endemic | 19 Participants |
| Place of Residence Rural | 12 Participants |
| Place of Residence Urban | 31 Participants |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment Argentina | 44 participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 43 |
| other Total, other adverse events | 32 / 44 | 31 / 43 |
| serious Total, serious adverse events | 0 / 44 | 0 / 43 |
Outcome results
None listed