NCT03431168

A Novel Regimen to Prevent Malaria and STI in Pregnant Women With HIV

The PREMISE Trial: A Novel Regimen to Prevent Malaria and Sexually Transmitted Infections in Pregnant Women With HIV

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 308 (actual)
• Sponsor: University of Alabama at Birmingham · Academic / Other
• Sex: Female
• Age: 16 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

More than 3 billion people worldwide are at risk of acquiring malaria and pregnant women living with HIV in Africa are at particular risk. An effective prophylaxis regimen capable of preventing malaria and other common perinatal infections would have great potential to improve adverse birth outcomes. The purpose of this randomized controlled trial is to evaluate a new combination prophylaxis regimen in pregnant women with HIV in Cameroon to determine its efficacy and safety.

Detailed description

The World Health Organization (WHO) recommends malaria prophylaxis for all pregnant women living in endemic areas in order to reduce maternal anemia, low birth weight and perinatal mortality by 25-45%. The most commonly used regimen is intermittently dosed sulfadoxine-pyrimethamine (SP).Unfortunately, SP prophylaxis is contraindicated for HIV-infected pregnant women since co-administration with TMPS (trimethoprim-sulfamethoxazole) causes serious adverse events. TMPS (Bactrim or Cotrimoxazole) is an effective, well-tolerated, low-cost antibiotic that is used as prophylaxis in HIV-patients with low CD4 counts. It has anti-malarial activity with prophylactic efficacy that is comparable to SP (30-90%). Daily TMPS is recommended as malaria prophylaxis in pregnant women with HIV in many African countries (including Cameroon) but malaria infection rates are high even when medication compliance is excellent; thus, new and improved options are urgently needed. Azithromycin (AZ) is a macrolide antibiotic with activity against malaria, a good safety profile in pregnancy and proven utility as a part of combination malaria prevention regimens (such as SP-AZ). It also has activity against sexually transmitted infections (STI) and perinatal pathogens, including chlamydia (CT), gonorrhea (GC), syphilis and GBS (Streptococcus agalactiae or Group B Streptococcus), a potential but understudied contributor to high rates of newborn sepsis and death in Africa. SP-AZ prophylaxis in HIV-uninfected pregnant women has been reported to reduce prevalence of low birth weight (RR 0.74, 95% confidence interval (CI) 0.6-0.9) and preterm delivery (RR 0.66, 95% CI 0.48-0.91) compared to SP alone. Thus, the central hypothesis is that a TMPS-AZ combination will be more effective than standard TMPS malaria prophylaxis in pregnant women with HIV, and that it will also decrease STI coinfection. Investigators plan a test-of-concept of the central hypothesis by conducting a double blinded, Phase II randomized controlled trial (RCT).

Conditions

• HIV
• Pregnancy Malaria
• Sexually Transmitted Infection

Interventions

Type	Name	Description
DRUG	Azithromycin/TMPS	2 tabs po daily x 3 days at enrollment and at each monthly follow up visit
DRUG	Placebo/TMPS	2 tabs po daily x 3 days at enrollment and at each monthly follow up visit

Timeline

• Start date: 2018-03-07
• Primary completion: 2021-01-01
• Completion: 2022-01-01
• First posted: 2018-02-13
• Last updated: 2023-11-27
• Results posted: 2022-05-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study