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

NCT ID: NCT03431168

Last Updated: 2023-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 308 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-07
• Study Completion Date: 2022-01-01

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).

Conditions

HIV; Pregnancy Malaria; Sexually Transmitted Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Azithromycin/TMPS

Azithromycin 1 gm po daily x 3 days at enrollment and at each 4 week follow up visit.

TMPS double strength 1 tablet po daily.

Group Type: ACTIVE_COMPARATOR

Azithromycin/TMPS

Intervention Type: DRUG

2 tabs po daily x 3 days at enrollment and at each monthly follow up visit

Placebo/TMPS

Azithromycin placebo 1 gm po daily x 3 days at enrollment and at each 4 week follow up visit.

TMPS double strength 1 tablet po daily.

Group Type: PLACEBO_COMPARATOR

Placebo/TMPS

Intervention Type: DRUG

2 tabs po daily x 3 days at enrollment and at each monthly follow up visit

Interventions

Azithromycin/TMPS

2 tabs po daily x 3 days at enrollment and at each monthly follow up visit

Intervention Type: DRUG

Placebo/TMPS

2 tabs po daily x 3 days at enrollment and at each monthly follow up visit

Intervention Type: DRUG

Other Intervention Names

Cotrimoxazole; Co-Trimoxazole

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).

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Jodie A. Dionne, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jodie A Dionne-Odom, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

References

Pons-Duran C, Wassenaar MJ, Yovo KE, Marin-Carballo C, Briand V, Gonzalez R. Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women. Cochrane Database Syst Rev. 2024 Sep 26;9(9):CD006689. doi: 10.1002/14651858.CD006689.pub3.

Reference Type: DERIVED

PMID: 39324693 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

IRB-300001112

Identifier Type: -

Identifier Source: org_study_id