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

The University of Alabama at Birmingham

Status and phase

Completed

Phase 2

Conditions

Pregnancy Malaria

Sexually Transmitted Infection

HIV

Treatments

Drug: Azithromycin/TMPS

Drug: Placebo/TMPS

Study type

Interventional

Funder types

Other

Identifiers

NCT03431168

IRB-300001112

Details and patient eligibility

About

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.

Full 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).

Enrollment

308 patients

Sex

Female

Ages

16 to 55 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Confirmed HIV-infection (documented in medical record)
Age ≥16 years
Confirmed pregnancy, <28 weeks estimated gestational age (by best obstetric estimate which may include ultrasound or fundal height and LMP)
Live singleton pregnancy
Receiving prenatal care at Mboppi Hospital or Mutengene Hospital
Plan to receive follow up prenatal care and deliver at study facility
Capable of providing written informed consent
Able and agree to come to facility for febrile episodes or acute illness during pregnancy (with reimbursement of transportation costs).
Agree to avoid antimalarial medications outside of study protocol.

Exclusion criteria

Severe anemia (last hemoglobin <6)
History of severe adverse reaction to co-trimoxazole or azithromycin
Active medical problem requiring inpatient evaluation at the time of screening
Intention of moving far away from the facility during pregnancy or not likely to return for follow up care or delivery
Signs or symptoms of early or active labor
History of severe cardiac disease (including congestive heart failure, severe valvular disease or arrhythmias).