Feasibility of Vaginal Progesterone to Reduce HIV-Associated Preterm Birth

Phase 4

Completed

Conditions: PreTerm Birth

Interventions: Drug: Placebo
Drug: Vaginal Progesterone

Registration Number: NCT02970552

Lead Sponsor: University of North Carolina, Chapel Hill

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 140

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Daily self-administered indistinguishable placebo
Vaginal Progesterone	Vaginal Progesterone	Daily self-administered vaginal progesterone

Primary Outcome Measures

Name	Time	Method
Adequate Adherence to Study Product	Enrollment through 36th gestational week, an overall total of up to 17 weeks	Number of participants who achieved adequate adherence to study product, defined as proper self-administration of at least 80% of prescribed study product doses, as measured by a dye stain assay of returned applicators

Secondary Outcome Measures

Name	Time	Method
Acceptability of Use of Vaginal Progesterone (VP)	At enrollment (20-24 weeks gestation), at 28 weeks gestation, and at 36 weeks gestation	Semi-structured interviews will be held with a random sample of participants who enroll and those who decline enrollment.
Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study	Late in pregnancy or postpartum	Number of participants reporting barriers and facilitators to study product adherence, returning used applicators, and retention in the study during a semi-structured interview. Participants were selected for an interview based on their overall adherence rates, including those with excellent adherence throughout the study and those with lower adherence rates early or late in their participation. A trained female staff member conducted each 30-minute interview using an interview guide. Interviews were audiotaped, transcribed, and translated into English as necessary.
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)	Late in pregnancy or postpartum	Number of participants reporting attitudes and practices related to participation in placebo controlled RCTs during a semi-structured interview. Participants were selected for an interview based on their overall adherence rates, including those with excellent adherence throughout the study and those with lower adherence rates early or late in their participation. A trained female staff member conducted each 30-minute interview using an interview guide. Participants were asked about their attitudes toward participation in the study and research in general as HIV-infected women taking ART and at risk of preterm birth, but they were not specifically asked about their underlying knowledge of these conditions. Interviews were audio-taped, transcribed, and translated into English as necessary.
Acceptability of a Vaginal Medication to Prevent Preterm Birth	Visit 9.0 (36 weeks of gestation)	Number of participants reporting specific attitudes about medications for the prevention of preterm birth (PTB), including acceptability of daily vaginal administration as measured on the Exit Satisfaction Survey using a Likert scale of five possible options ranging from strongly agree to strongly disagree. The form included a range of facial illustrations to facilitate comprehension of the answer choices, particularly for illiterate participants.
Reported Barriers to Adherence to Study Product	Visit 9.0 (36 weeks of gestation)	Number of participants reporting challenges with taking the study medication as measured on the Exit Satisfaction Survey. The survey was administered by a study nurse who asked each participant what was the hardest part about taking the medication and presented all possible answer choices. Participant were asked to select only one answer.
Sensitivity, Specificity, and Predictive Value of Dose Diaries	Enrollment through 36th gestational week, an overall total of up to 17 weeks	Comparison of self-reported adherence rates (Dose Diary/DD) and use of returned applicators measured by dye stain assay (DSA)
Enrollment of Eligible Participants	Screening through Enrollment	Number of eligible participants who enrolled in the study
Ascertainment of Date of Delivery and Infant Vital Status	Visit 10.0 (Delivery)	Number of women for whom date of delivery and infant vital status at birth was ascertained
Preliminary Efficacy	Visit 10.0 (Delivery)	Number of participants delivering before 34 and 37 completed weeks of gestation, grouped based on whether the participant went into labor spontaneously or was induced by a provider
Birth Weight	Visit 10.0 (Delivery)	Number of participants with neonates weighing less than 2500 grams at birth
Stillbirth	Visit 10.0 (Delivery)	Number of participants who experienced a stillbirth
Adverse Events	Enrollment through Visit 10.0 (Delivery)	Number of women experiencing a serious adverse event or event that resulted in study product discontinuation