Study to Improve Survival Among HIV-Exposed Infants in Botswana (Mpepu)

September 5, 2019 updated by: Roger Shapiro, Harvard School of Public Health (HSPH)

A Randomized Study of Cotrimoxazole Prophylaxis and Longer Breastfeeding Duration to Improve Survival Among HIV-Exposed Infants in Botswana

The purpose of this study is to find ways to improve infant health and survival among infants whose mothers are HIV-infected but who do not themselves have HIV.

Study Overview

Detailed Description

As improved MTCT prevention interventions reduce the number of HIV-infected infants in the antepartum and peripartum periods, interventions to improve HIV-free survival among HIV-uninfected infants are needed. Morbidity and mortality are increased among HIV-uninfected infants born to HIV-infected mothers, and reduced infant survival among HIV-exposed infants may lead to as many deaths as HIV infection itself. In Botswana, the use of formula feeding or shorter breastfeeding may worsen the problem of early infant mortality among HIV-exposed infants.

The study will enroll pregnant or postpartum HIV-1-infected women, and their HIV-uninfected infants in Botswana. At 2-4 weeks of age, live HIV-uninfected infants will be randomized to receive either double-blinded cotrimoxazole (CTX) or placebo from 2-4 weeks through 15 months. In addition, breastfeeding (BF) infants will be randomized to BF until either 6 or 12 months of age. Children will be followed prospectively until 18 months of age. The primary endpoint will be survival at 18 months comparing all infants in the CTX vs. placebo arms, and by randomized duration of BF among those BF at randomization. Secondary endpoints will evaluate survival and morbidity/mortality at 12 and 15 months; HIV-free survival to 18 months; and the safety of CTX prophylaxis. Secondary observational objectives include comparing MTCT and mortality by initial feeding method (formula feeding or any BF > 1 month), and an analysis of maternal characteristics as predictors for initial feeding choice and HIV-free survival. All women and infants will receive standard antenatal and peripartum prophylaxis from the Botswana government for MTCT prevention (PMTCT), and will choose a feeding method with counseling. Breastfeeding infants will receive infant nevirapine (NVP) prophylaxis or will be protected from MTCT by the use of maternal HAART.

Study Type

Interventional

Enrollment (Anticipated)

3724

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Gaborone, Botswana
        • Princess Marina Hospital
      • Lobatse, Botswana
        • Athlone Hospital
      • Molepolole, Botswana
        • Scottish Livingstone Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • HIV-infected women, > 26 weeks gestation and < 34 days postpartum.
  • Women must be ¬> 18 years of age and willing/able to sign informed consent.
  • Women and infants must be able to follow up regularly at a study clinic through 18 months postpartum.
  • For Feeding Randomization Only: Women must be willing to breastfeed for up to 12 months, and to stop at 6 months, depending upon their feeding assignment.

Exclusion Criteria:

  • Antepartum women: Known infant anomalies resulting in a high probability that the infant will not survive to 18 months.
  • Postpartum women: Known HIV-infected infant, or infant medical condition making survival to 18 months unlikely.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: infant cotrimoxazole
100mg/20mg per day (or 2.5 mL of syrup from a 200mg/40mg per 5mL suspension) from 1-6 months, followed by 200mg/40mg per day (or 5 mL of syrup from a 200mg/40mg per 5 mL suspension) from 6 to 12 months
Other Names:
  • Trimethoprim-Sulfamethoxazole Combination
Placebo Comparator: infant placebo
100mg/20mg per day (or 2.5 mL of syrup from a 200mg/40mg per 5mL suspension) from 1-6 months, followed by 200mg/40mg per day (or 5 mL of syrup from a 200mg/40mg per 5 mL suspension) from 6 to 12 months
Active Comparator: exclusive breastfeeding for 6 months
Breastfeeding for 6 months, followed by formula feeding for 6 month. Breastfeeding infants will be prophylaxed with maternal highly active antiretroviral therapy (HAART) (if available) or with infant nevirapine.
Active Comparator: exclusive breastfeeding for 12 months
Breastfeeding infants will be prophylaxed with maternal HAART (if available) or with infant nevirapine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: 18 months of age
The primary outcome measure is survival at 18 months comparing all infants in the CTX vs. placebo arms, and by randomized duration of breastfeeding among those breastfeeding at randomization.
18 months of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HIV-free Survival
Time Frame: 18 months of age
Secondary outcome measures will evaluate HIV-free survival between 4 weeks and 18 months among infants randomized to either 6 months or 12 months of breastfeeding.
18 months of age
Safety of CTX prophylaxis
Time Frame: 18 months
Secondary outcome measures will evaluate the safety of CTX prophylaxis through 18 months
18 months
Morbidity and mortality
Time Frame: 18 months of age
Secondary outcome measures will evaluate morbidity and mortality to 18 months.
18 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

October 1, 2018

Study Registration Dates

First Submitted

October 22, 2010

First Submitted That Met QC Criteria

October 26, 2010

First Posted (Estimate)

October 28, 2010

Study Record Updates

Last Update Posted (Actual)

September 9, 2019

Last Update Submitted That Met QC Criteria

September 5, 2019

Last Verified

September 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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