Trial Outcomes & Findings for Feasibility of Vaginal Progesterone to Reduce HIV-Associated Preterm Birth (NCT NCT02970552)
NCT ID: NCT02970552
Last Updated: 2020-02-06
Results Overview
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
COMPLETED
PHASE4
140 participants
Enrollment through 36th gestational week, an overall total of up to 17 weeks
2020-02-06
Participant Flow
Participant milestones
| Measure |
Vaginal Progesterone
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Overall Study
STARTED
|
70
|
70
|
|
Overall Study
COMPLETED
|
67
|
67
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Feasibility of Vaginal Progesterone to Reduce HIV-Associated Preterm Birth
Baseline characteristics by cohort
| Measure |
Vaginal Progesterone
n=70 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=70 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
Total
n=140 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
70 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
70 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
70 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Zambia
|
70 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Enrollment through 36th gestational week, an overall total of up to 17 weeksPopulation: Participants who returned for at least one follow-up study visit following enrollment
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
Outcome measures
| Measure |
Vaginal Progesterone
n=68 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=69 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Adequate Adherence to Study Product
|
62 Participants
|
63 Participants
|
SECONDARY outcome
Timeframe: At enrollment (20-24 weeks gestation), at 28 weeks gestation, and at 36 weeks gestationPopulation: Activation was delayed by 6 months because of a protracted regulatory process. Resulting low resources limited investigators' ability to conduct interviews at all specified times or with decliners. Investigators did conduct a single interview with a sample of participants late in pregnancy or postpartum; these data are captured in outcomes #3 and 4
Semi-structured interviews will be held with a random sample of participants who enroll and those who decline enrollment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Late in pregnancy or postpartumPopulation: A sample of enrolled participants selected to participate in a semi-structured interview. Investigators included 30 trial participants based on expectations regarding saturation of qualitative themes.
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.
Outcome measures
| Measure |
Vaginal Progesterone
n=19 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=11 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study
Reported any barriers to medication use
|
7 Participants
|
1 Participants
|
|
Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study
Discontinued med due to challenges or discomfort
|
0 Participants
|
0 Participants
|
|
Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study
Reported any facilitators to medication use
|
19 Participants
|
11 Participants
|
|
Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study
Reported barrier to returning used applicators
|
0 Participants
|
0 Participants
|
|
Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study
Reported barriers to returning for study visits
|
2 Participants
|
0 Participants
|
|
Reported Barriers and Facilitators to Adherence to Study Product, Returning Used Applicators, and Retention in the Study
Reported positive experience with study clinic
|
19 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Late in pregnancy or postpartumPopulation: A sample of enrolled participants selected to participate in a semi-structured interview. Investigators included 30 trial participants based on expectations regarding saturation of qualitative themes.
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.
Outcome measures
| Measure |
Vaginal Progesterone
n=19 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=11 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
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)
Belief that being in the study prevented PTB
|
15 Participants
|
6 Participants
|
|
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)
Belief that women might refuse a placebo RCT
|
9 Participants
|
3 Participants
|
|
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)
Disclosed study participation to others
|
19 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: Visit 9.0 (36 weeks of gestation)Population: 131 randomized participants who completed an exit satisfaction survey
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.
Outcome measures
| Measure |
Vaginal Progesterone
n=67 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=64 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Happy that I took part in the study · Strongly disagree
|
0 Participants
|
0 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Happy that I took part in the study · Disagree
|
0 Participants
|
0 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Happy that I took part in the study · Neutral
|
0 Participants
|
1 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Happy that I took part in the study · Agree
|
1 Participants
|
3 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Happy that I took part in the study · Strongly agree
|
66 Participants
|
60 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Did not mind taking daily vaginal medication · Strongly disagree
|
0 Participants
|
0 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Did not mind taking daily vaginal medication · Disagree
|
0 Participants
|
0 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Did not mind taking daily vaginal medication · Neutral
|
0 Participants
|
1 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Did not mind taking daily vaginal medication · Agree
|
9 Participants
|
3 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Did not mind taking daily vaginal medication · Strongly agree
|
58 Participants
|
60 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Would choose daily vag med over wkly injection · Strongly disagree
|
13 Participants
|
15 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Would choose daily vag med over wkly injection · Disagree
|
3 Participants
|
0 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Would choose daily vag med over wkly injection · Neutral
|
1 Participants
|
2 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Would choose daily vag med over wkly injection · Agree
|
7 Participants
|
5 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Would choose daily vag med over wkly injection · Strongly agree
|
43 Participants
|
42 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Other women would like to take med to stop PTB · Strongly disagree
|
1 Participants
|
0 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Other women would like to take med to stop PTB · Disagree
|
1 Participants
|
2 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Other women would like to take med to stop PTB · Neutral
|
9 Participants
|
3 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Other women would like to take med to stop PTB · Agree
|
16 Participants
|
15 Participants
|
|
Acceptability of a Vaginal Medication to Prevent Preterm Birth
Other women would like to take med to stop PTB · Strongly agree
|
40 Participants
|
44 Participants
|
SECONDARY outcome
Timeframe: Visit 9.0 (36 weeks of gestation)Population: 131 randomized participants who completed an exit satisfaction survey
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.
Outcome measures
| Measure |
Vaginal Progesterone
n=67 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=64 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Reported Barriers to Adherence to Study Product
Remembering to take it
|
0 Participants
|
2 Participants
|
|
Reported Barriers to Adherence to Study Product
Didn't like using the product
|
0 Participants
|
0 Participants
|
|
Reported Barriers to Adherence to Study Product
Obtaining refills at clinic
|
0 Participants
|
0 Participants
|
|
Reported Barriers to Adherence to Study Product
Disclosing participation to partner or family
|
0 Participants
|
0 Participants
|
|
Reported Barriers to Adherence to Study Product
Inserting the medication
|
1 Participants
|
0 Participants
|
|
Reported Barriers to Adherence to Study Product
Nothing was hard about taking the medication
|
66 Participants
|
62 Participants
|
SECONDARY outcome
Timeframe: Enrollment through 36th gestational week, an overall total of up to 17 weeksPopulation: Dose diaries completed by randomized participants returned at each follow-up visit, reported among participants who returned for at least 1 visit. Outcome assessed the reliability of dose diaries against DSA gold standard regardless of study arm to measure feasibility for future use. Estimates are presented in aggregate per original analysis plan.
Comparison of self-reported adherence rates (Dose Diary/DD) and use of returned applicators measured by dye stain assay (DSA)
Outcome measures
| Measure |
Vaginal Progesterone
n=12256 Daily dose diaries
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Sensitivity, Specificity, and Predictive Value of Dose Diaries
Sensitivity Pr(DD+/DSA+)
|
0.999 Proportion of ppts correctly identified
Interval 0.999 to 1.0
|
—
|
|
Sensitivity, Specificity, and Predictive Value of Dose Diaries
Specificity Pr(DD-/DSA-)
|
0.571 Proportion of ppts correctly identified
Interval 0.521 to 0.619
|
—
|
|
Sensitivity, Specificity, and Predictive Value of Dose Diaries
Positive Predictive Value Pr(DSA+/DD+)
|
0.985 Proportion of ppts correctly identified
Interval 0.983 to 0.987
|
—
|
|
Sensitivity, Specificity, and Predictive Value of Dose Diaries
Negative Predictive Value Pr(DSA-/DD-)
|
0.975 Proportion of ppts correctly identified
Interval 0.946 to 0.991
|
—
|
SECONDARY outcome
Timeframe: Screening through EnrollmentPopulation: Women with a completed ultrasound who were eligible for study screening procedures
Number of eligible participants who enrolled in the study
Outcome measures
| Measure |
Vaginal Progesterone
n=208 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Enrollment of Eligible Participants
Successfully Screened
|
154 Participants
|
—
|
|
Enrollment of Eligible Participants
Randomized
|
140 Participants
|
—
|
SECONDARY outcome
Timeframe: Visit 10.0 (Delivery)Population: All enrolled participants
Number of women for whom date of delivery and infant vital status at birth was ascertained
Outcome measures
| Measure |
Vaginal Progesterone
n=70 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=70 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Ascertainment of Date of Delivery and Infant Vital Status
|
67 Participants
|
67 Participants
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Vaginal Progesterone
n=67 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=67 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Preliminary Efficacy
Spontaneous preterm birth <34 weeks
|
4 Participants
|
6 Participants
|
|
Preliminary Efficacy
Preterm birth <37 weeks
|
9 Participants
|
10 Participants
|
|
Preliminary Efficacy
Spontaneous preterm birth <37 weeks
|
8 Participants
|
10 Participants
|
|
Preliminary Efficacy
Preterm birth <34 weeks
|
5 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Visit 10.0 (Delivery)Population: Randomized participants with birth weight data ascertained
Number of participants with neonates weighing less than 2500 grams at birth
Outcome measures
| Measure |
Vaginal Progesterone
n=64 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=64 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Birth Weight
|
9 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Visit 10.0 (Delivery)Number of participants who experienced a stillbirth
Outcome measures
| Measure |
Vaginal Progesterone
n=67 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=67 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Stillbirth
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Enrollment through Visit 10.0 (Delivery)Number of women experiencing a serious adverse event or event that resulted in study product discontinuation
Outcome measures
| Measure |
Vaginal Progesterone
n=70 Participants
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=70 Participants
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Adverse Events
Pre-eclampsia
|
1 Participants
|
0 Participants
|
|
Adverse Events
Stillbirth
|
2 Participants
|
2 Participants
|
Adverse Events
Vaginal Progesterone
Placebo
Serious adverse events
| Measure |
Vaginal Progesterone
n=70 participants at risk
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=70 participants at risk
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Stillbirth
|
2.9%
2/70 • Number of events 2 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
2.9%
2/70 • Number of events 2 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
|
Pregnancy, puerperium and perinatal conditions
Pre-eclampsia
|
1.4%
1/70 • Number of events 1 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
0.00%
0/70 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
Other adverse events
| Measure |
Vaginal Progesterone
n=70 participants at risk
Daily self-administered vaginal progesterone
Vaginal Progesterone: 200 mg micronized vaginal progesterone suppository
|
Placebo
n=70 participants at risk
Daily self-administered indistinguishable placebo
Placebo: Indistinguishable placebo vaginal suppository
|
|---|---|---|
|
General disorders
Headache
|
21.4%
15/70 • Number of events 15 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
14.3%
10/70 • Number of events 10 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
|
Gastrointestinal disorders
Nausea/Vomiting
|
8.6%
6/70 • Number of events 6 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
8.6%
6/70 • Number of events 6 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
|
General disorders
Lower Abdominal Pain
|
11.4%
8/70 • Number of events 8 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
7.1%
5/70 • Number of events 5 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
|
Reproductive system and breast disorders
Vaginal Itching/Burning
|
7.1%
5/70 • Number of events 5 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
11.4%
8/70 • Number of events 8 • From the time of enrollment through delivery, a total of approximately 16-20 weeks.
|
Additional Information
Joan Price, MD, MPH
University of North Carolina at Chapel Hill
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place