Clinical trial NCT03431168: A Novel Regimen to Prevent Malaria and STI in Pregnant Women With HIV
Official title: The PREMISE Trial: A Novel Regimen to Prevent Malaria and Sexually Transmitted Infections in Pregnant Women With HIV
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV
Pregnancy Malaria
Sexually Transmitted Infection
Keywords: STI Prevention
Cameroon
sub-Saharan Africa
HIV pregnancy
Malaria in pregnancy
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2018-02-13
Enrollment: 308
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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).

Eligibility criteria: 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).

Primary outcomes:
measure: Plasmodium Falciparum Peripheral Parasitemia
timeFrame: At end of pregnancy (>35 weeks) or at delivery
measure: Proportion With Composite STI Outcome
timeFrame: will be measured in both groups (>35 weeks) or at delivery
Secondary outcomes:
measure: Low Birthweight (<2500 Grams)
timeFrame: at birth
measure: Proportion With Adverse Birth Outcomes
timeFrame: Birth outcomes will be measured at birth for all outcomes except early neonatal mortality defined as within 7 days of birth. Early neonatal mortality will be assessed at a six week follow up phone call.
measure: Maternal Adherence to the Prophylactic Regimen
timeFrame: Adherence of study medication taken at home will be documented from the date of randomization until the time of delivery, assessed up to 42 weeks.
measure: Proportion of Participants With Symptomatic Malaria
timeFrame: From the date of randomization until the time of delivery, assessed up to 42 weeks.
measure: Proportion With Placental Malaria
timeFrame: At delivery
measure: Proportion With Maternal Anemia and Severe Maternal Anemia
timeFrame: At the end of pregnancy (>35 weeks) or at delivery
measure: Composite STI Measure (Including All STI Tests)
timeFrame: After 35 weeks GA or at delivery
measure: GBS Colonization
timeFrame: at or near term or at delivery
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Jodie A Dionne-Odom, MD
role: PRINCIPAL_INVESTIGATOR
References: