Feasibility of Vaginal Progesterone to Reduce HIV-Associated Preterm Birth (VP)

A Pilot Study of Vaginal Progesterone to Reduce Preterm Birth Among Women Receiving Antiretroviral Therapy in Pregnancy

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.

Study Overview

• Status: Completed
• Conditions: PreTerm Birth
• Intervention / Treatment: Drug: Vaginal Progesterone; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 4

Contacts and Locations

Study Locations

• Zambia
  • Lusaka, Zambia
    • Kamwala District Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vaginal Progesterone; Daily self-administered vaginal progesterone	Drug: Vaginal Progesterone; 200 mg micronized vaginal progesterone suppository
Placebo Comparator: Placebo; Daily self-administered indistinguishable placebo	Drug: Placebo; Indistinguishable placebo vaginal suppository

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adequate Adherence to Study Product	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	Enrollment through 36th gestational week, an overall total of up to 17 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability of Use of Vaginal Progesterone (VP)	Semi-structured interviews will be held with a random sample of participants who enroll and those who decline enrollment.	At enrollment (20-24 weeks gestation), at 28 weeks gestation, and at 36 weeks gestation
Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study	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.	Late in pregnancy or postpartum
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)	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.	Late in pregnancy or postpartum
Acceptability of a Vaginal Medication to Prevent Preterm Birth	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.	Visit 9.0 (36 weeks of gestation)
Reported Barriers to Adherence to Study Product	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.	Visit 9.0 (36 weeks of gestation)
Sensitivity, Specificity, and Predictive Value of Dose Diaries	Comparison of self-reported adherence rates (Dose Diary/DD) and use of returned applicators measured by dye stain assay (DSA)	Enrollment through 36th gestational week, an overall total of up to 17 weeks
Enrollment of Eligible Participants	Number of eligible participants who enrolled in the study	Screening through Enrollment
Ascertainment of Date of Delivery and Infant Vital Status	Number of women for whom date of delivery and infant vital status at birth was ascertained	Visit 10.0 (Delivery)
Preliminary Efficacy	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	Visit 10.0 (Delivery)
Birth Weight	Number of participants with neonates weighing less than 2500 grams at birth	Visit 10.0 (Delivery)
Stillbirth	Number of participants who experienced a stillbirth	Visit 10.0 (Delivery)
Adverse Events	Number of women experiencing a serious adverse event or event that resulted in study product discontinuation	Enrollment through Visit 10.0 (Delivery)

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Jeffrey Stringer, MD, University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

• 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. Erratum In: Pilot Feasibility Stud. 2017 Oct 24;3:48.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): November 13, 2018
• Study Completion (Actual): November 13, 2018

Study Registration Dates

• First Submitted: November 17, 2016
• First Submitted That Met QC Criteria: November 18, 2016
• First Posted (Estimate): November 22, 2016

Study Record Updates

• Last Update Posted (Actual): February 6, 2020
• Last Update Submitted That Met QC Criteria: January 27, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Adherence; Feasibility; HIV; PreTerm Birth; ART; Vaginal Progesterone
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 16-2174; 1R21HD090987-01 (U.S. NIH Grant/Contract); Z 31606 (Other Identifier: IGHID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes