Clinical trial NCT02970552: Feasibility of Vaginal Progesterone to Reduce HIV-Associated Preterm Birth
Official title: A Pilot Study of Vaginal Progesterone to Reduce Preterm Birth Among Women Receiving Antiretroviral Therapy in Pregnancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: PreTerm Birth
Keywords: PreTerm Birth
HIV
Vaginal Progesterone
ART
Adherence
Feasibility
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2016-11-22
Enrollment: 140
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: More than 1.5 million HIV-infected women become pregnant each year. Approximately half have access to antiretroviral therapy (ART), but all are at increased risk of preterm birth (PTB). Vaginal progesterone (VP) is a promising and cost-effective intervention to prevent PTB that should be studied in this high-risk population. This pilot study will provide critical insight into the feasibility of a phase III trial by determining whether women are willing to participate, to adhere to study drug, and to complete follow-up.

Detailed description: This will be a mixed method study to evaluate the feasibility and acceptability of a trial of VP to prevent PTB among HIV-infected Zambian women. To assess the feasibility of a full-scale clinical trial, the investigators will implement a pilot two-arm, double-masked, placebo-controlled trial of VP among HIV-infected women in antenatal care in Lusaka, Zambia. Participants will be randomly assigned to either daily self-administered VP or indistinguishable placebo prior to 24 weeks gestational age. In this pilot study, the investigators will be able to estimate study uptake, adherence to study product and protocol, and study retention. To assess the acceptability of a trial to test VP among HIV-infected women in Zambia, the investigators will employ a qualitative approach of longitudinal semi-structured interviews among women agreeing to trial participation and one-time semi-structured interviews (SSIs) among those who decline to participate.

Eligibility criteria: Inclusion Criteria:

1. 18 years of age or older
2. viable intrauterine pregnancy confirmed by ultrasound
3. presentation to antenatal care prior to 24 weeks gestation
4. antibody-confirmed HIV-1 infection
5. initiating or continuing ART treatment in pregnancy
6. ability and willingness to provide written informed consent
7. willing to adhere to study visit schedule

Exclusion Criteria:

1. multiple gestation
2. non-research indication for antenatal progesterone (i.e. prior spontaneous PTB and/or cervical length \<20mm on screening ultrasound)
3. planned or in situ cervical cerclage
4. evidence of threatened abortion, preterm labor, or ruptured membranes
5. major fetal anomaly detected on screening ultrasound
6. known uterine anomaly
7. known or suspected allergy or contraindication to VP or placebo components

Primary outcomes:
measure: Adequate Adherence to Study Product
timeFrame: Enrollment through 36th gestational week, an overall total of up to 17 weeks
Secondary outcomes:
measure: Acceptability of Use of Vaginal Progesterone (VP)
timeFrame: At enrollment (20-24 weeks gestation), at 28 weeks gestation, and at 36 weeks gestation
measure: Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study
timeFrame: Late in pregnancy or postpartum
measure: Summary of Reported Knowledge, Attitudes, and Practices Related to HIV, Antiretroviral Therapy (ART), Risk of Preterm Birth, and Participation in Placebo Controlled Randomized Clinical Trials (RCTs)
timeFrame: Late in pregnancy or postpartum
measure: Acceptability of a Vaginal Medication to Prevent Preterm Birth
timeFrame: Visit 9.0 (36 weeks of gestation)
measure: Reported Barriers to Adherence to Study Product
timeFrame: Visit 9.0 (36 weeks of gestation)
measure: Sensitivity, Specificity, and Predictive Value of Dose Diaries
timeFrame: Enrollment through 36th gestational week, an overall total of up to 17 weeks
measure: Enrollment of Eligible Participants
timeFrame: Screening through Enrollment
measure: Ascertainment of Date of Delivery and Infant Vital Status
timeFrame: Visit 10.0 (Delivery)
measure: Preliminary Efficacy
timeFrame: Visit 10.0 (Delivery)
measure: Birth Weight
timeFrame: Visit 10.0 (Delivery)
measure: Stillbirth
timeFrame: Visit 10.0 (Delivery)
measure: Adverse Events
timeFrame: Enrollment through Visit 10.0 (Delivery)
Other outcomes:
Locations:
city: Lusaka
country: Zambia
facility: Kamwala District Health Centre
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Jeffrey Stringer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Price JT, Mollan KR, Fuseini NM, Freeman BL, Mulenga HB, Corbett AH, Vwalika B, Stringer JSA. Vaginal progesterone to reduce preterm birth among HIV-infected pregnant women in Zambia: a feasibility study protocol. Pilot Feasibility Stud. 2017 Jul 18;4:21. doi: 10.1186/s40814-017-0170-7. eCollection 2018.