HIV InfectionsPhase 2MpepuNCT01229761

Study to Improve Survival Among HIV-Exposed Infants in Botswana

A Phase 2 study testing cotrimoxazole prophylaxis, exclusive breastfeeding until 6 months of age and breastfeeding for 12 months in people with HIV Infections and Neutropenia, run by Harvard School of Public Health (HSPH) at 3 sites in Botswana.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: HIV Infections, Neutropenia, Anemia
What is being tested?: cotrimoxazole prophylaxis, exclusive breastfeeding until 6 months of age and breastfeeding for 12 months
Type of treatment: Pill or oral medicine, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 3,724 participants
Where: 3 sitesBotswana
Study dates: May 2011to Oct 2018
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

3 sites in 1 country.

Botswana3 sites

Princess Marina Hospital
Gaborone
Athlone Hospital
Lobatse
Scottish Livingstone Hospital
Molepolole

Other trials in Botswana

About this study

Official title: 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.

Read the 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.

Conditions: HIV Infections, Neutropenia, Anemia
Being tested: cotrimoxazole prophylaxis, cotrimoxazole placebo, exclusive breastfeeding until 6 months of age, breastfeeding for 12 months
Keywords: HIV, Trimethoprim-Sulfamethoxazole Combination, Breast Feeding, Infant Mortality, Morbidity, Botswana, Africa, Infectious disease transmission, vertical, adverse drug event
Medical subject headings: HIV Infections, Neutropenia, Anemia, Breast Feeding, Infant Death, Drug-Related Side Effects and Adverse Reactions

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

cotrimoxazole prophylaxisDrug
Also called Trimethoprim-Sulfamethoxazole Combination
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
cotrimoxazole placeboDrug
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
exclusive breastfeeding until 6 months of ageBehavioural
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.
breastfeeding for 12 monthsBehavioural
Breastfeeding infants will be prophylaxed with maternal HAART (if available) or with infant nevirapine.

Study groups in NCT01229761
Study group	Role	What they receive
infant cotrimoxazole	Active comparator	Not described Receives: Drug: cotrimoxazole prophylaxis
infant placebo	Placebo comparator	Not described Receives: Drug: cotrimoxazole placebo
exclusive breastfeeding for 6 months	Active comparator	Not described Receives: Behavioral: exclusive breastfeeding until 6 months of age
exclusive breastfeeding for 12 months	Active comparator	Not described Receives: Behavioral: breastfeeding for 12 months

What is being measured

The primary outcome is the main question the study is designed to answer.

Survival
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.
Measured: 18 months of age

Secondary outcomes (3)

HIV-free Survival
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.
Measured: 18 months of age
Safety of CTX prophylaxis
Secondary outcome measures will evaluate the safety of CTX prophylaxis through 18 months
Measured: 18 months
Morbidity and mortality
Secondary outcome measures will evaluate morbidity and mortality to 18 months.
Measured: 18 months of age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2011Oct 2018

First posted28 Oct 2010 (estimated)
Study startMay 2011
Primary completionMar 2015
Study completionOct 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 3,724 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01229761
Sponsor's protocol ID: 18677
Other IDs: R01HD061265
Acronym: Mpepu
Status last verified: Sep 2019
First submitted: 22 Oct 2010
Last updated: 9 Sep 2019
Results posted: No
Data monitoring committee: Yes

Publications

Powis KM, Souda S, Lockman S, Ajibola G, Bennett K, Leidner J, Hughes MD, Moyo S, van Widenfelt E, Jibril HB, Makhema J, Essex M, Shapiro RL. Cotrimoxazole prophylaxis was associated with enteric commensal bacterial resistance among HIV-exposed infants in a randomized controlled trial, Botswana. J Int AIDS Soc. 2017 Nov;20(3):e25021. doi: 10.1002/jia2.25021.
PubMed 29119726
Lockman S, Hughes M, Powis K, Ajibola G, Bennett K, Moyo S, van Widenfelt E, Leidner J, McIntosh K, Mazhani L, Makhema J, Essex M, Shapiro R. Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial. Lancet Glob Health. 2017 May;5(5):e491-e500. doi: 10.1016/S2214-109X(17)30143-2.
PubMed 28395844
Ajibola G, Zash R, Shapiro RL, Batlang O, Botebele K, Bennett K, Chilisa F, Widenfelt EV, Makhema J, Lockman S, Holmes LB, Powis KM. Detecting congenital malformations - Lessons learned from the Mpepu study, Botswana. PLoS One. 2017 Mar 24;12(3):e0173800. doi: 10.1371/journal.pone.0173800. eCollection 2017.
PubMed 28339500

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder

All HIV Infections trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Study of Cotrimoxazole Prophylaxis and Longer Breastfeeding Duration to Improve Survival Among HIV-Exposed Infants in Botswana
ClinicalTrials.gov ID: NCT01229761
Acronym / sponsor ID: Mpepu / 18677
Conditions: HIV Infections, Neutropenia, Anemia
Keywords: HIV, Trimethoprim-Sulfamethoxazole Combination, Breast Feeding, Infant Mortality, Morbidity, Botswana, Africa, Infectious disease transmission, vertical
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 3,724 participants (estimated)
Lead sponsor: Harvard School of Public Health (HSPH)University, hospital or other
Collaborators: Harvard Medical School (HMS and HSDM), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Allergy and Infectious Diseases (NIAID)
Study start: May 2011
Primary completion: Mar 2015 (actual)
Study completion: Oct 2018 (actual)
First posted: 28 Oct 2010 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
infant cotrimoxazole	Active comparator	Drug: cotrimoxazole prophylaxis
infant placebo	Placebo comparator	Drug: cotrimoxazole placebo
exclusive breastfeeding for 6 months	Active comparator	Behavioral: exclusive breastfeeding until 6 months of age
exclusive breastfeeding for 12 months	Active comparator	Behavioral: breastfeeding for 12 months

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (2 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
cotrimoxazole prophylaxisAlso: Trimethoprim-Sulfamethoxazole Combination100mg/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	Drug	infant cotrimoxazole
cotrimoxazole placebo100mg/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	Drug	infant placebo
exclusive breastfeeding until 6 months of ageBreastfeeding 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.	Behavioural	exclusive breastfeeding for 6 months
breastfeeding for 12 monthsBreastfeeding infants will be prophylaxed with maternal HAART (if available) or with infant nevirapine.	Behavioural	exclusive breastfeeding for 12 months

Primary outcome

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.

3 secondary outcomes

HIV-free Survival
Time frame: 18 months of age
Safety of CTX prophylaxis
Time frame: 18 months
Morbidity and mortality
Time frame: 18 months of age

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2019.
Derived from this study: PubMed 29119726Powis KM, Souda S, Lockman S, Ajibola G, Bennett K, Leidner J, Hughes MD, Moyo S, van Widenfelt E, Jibril HB, Makhema J, Essex M, Shapiro RL. Cotrimoxazole prophylaxis was associated with enteric commensal bacterial resistance among HIV-exposed infants in a randomized controlled trial, Botswana. J Int AIDS Soc. 2017 Nov;20(3):e25021. doi: 10.1002/jia2.25021.
Derived from this study: PubMed 28395844Lockman S, Hughes M, Powis K, Ajibola G, Bennett K, Moyo S, van Widenfelt E, Leidner J, McIntosh K, Mazhani L, Makhema J, Essex M, Shapiro R. Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial. Lancet Glob Health. 2017 May;5(5):e491-e500. doi: 10.1016/S2214-109X(17)30143-2.
Derived from this study: PubMed 28339500Ajibola G, Zash R, Shapiro RL, Batlang O, Botebele K, Bennett K, Chilisa F, Widenfelt EV, Makhema J, Lockman S, Holmes LB, Powis KM. Detecting congenital malformations - Lessons learned from the Mpepu study, Botswana. PLoS One. 2017 Mar 24;12(3):e0173800. doi: 10.1371/journal.pone.0173800. eCollection 2017.
Shapiro RL et al. Similar mortality with cotrimoxazole vs. placebo in HIV-exposed uninfected children, Conference on Retroviruses and Opportunistic Infections (CROI 2016), Boston, abstract 37.Link provided by the sponsor.

Related trials for HIV Infections

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Shahin Lockman, MD, MS principal investigator

Harvard School of Public Health (HSPH)

Roger L Shapiro, MD, MPH principal investigator

Harvard School of Public Health (HSPH)

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Botswana. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Survival (time frame: 18 months of age). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01229761, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2019.