Trial Outcomes & Findings for Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth (NCT NCT02913495)
NCT ID: NCT02913495
Last Updated: 2026-02-24
Results Overview
Incidence of gestational age of delivery less than 37 weeks
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
210 participants
Primary outcome timeframe
up to 9 months (delivery)
Results posted on
2026-02-24
Participant Flow
Enrollment 2016 - 2021
5 excluded (N=2 miscarriage, N=3 withdrawal) prior to randomization
Participant milestones
| Measure |
Vaginal Progesterone
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Overall Study
STARTED
|
102
|
103
|
|
Overall Study
COMPLETED
|
94
|
94
|
|
Overall Study
NOT COMPLETED
|
8
|
9
|
Reasons for withdrawal
| Measure |
Vaginal Progesterone
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
5
|
|
Overall Study
Pregnancy termination
|
1
|
0
|
|
Overall Study
Miscarriage<16wk
|
2
|
1
|
|
Overall Study
Placenta previa
|
0
|
1
|
Baseline Characteristics
Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth
Baseline characteristics by cohort
| Measure |
Vaginal Progesterone
n=94 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=94 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
Total
n=188 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
30.2 years
STANDARD_DEVIATION 5.7 • n=58 Participants
|
28.9 years
STANDARD_DEVIATION 5.2
|
29.5 years
STANDARD_DEVIATION 5.5 • n=1 Participants
|
|
Sex: Female, Male
Female
|
94 Participants
n=58 Participants
|
94 Participants
|
188 Participants
n=1 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=58 Participants
|
0 Participants
|
0 Participants
n=1 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
21 Participants
n=58 Participants
|
24 Participants
|
45 Participants
n=1 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
73 Participants
n=58 Participants
|
70 Participants
|
143 Participants
n=1 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=58 Participants
|
0 Participants
|
0 Participants
n=1 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=58 Participants
|
0 Participants
|
0 Participants
n=1 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=58 Participants
|
0 Participants
|
1 Participants
n=1 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=58 Participants
|
0 Participants
|
0 Participants
n=1 Participants
|
|
Race (NIH/OMB)
Black or African American
|
42 Participants
n=58 Participants
|
51 Participants
|
93 Participants
n=1 Participants
|
|
Race (NIH/OMB)
White
|
47 Participants
n=58 Participants
|
43 Participants
|
90 Participants
n=1 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=58 Participants
|
0 Participants
|
0 Participants
n=1 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=58 Participants
|
0 Participants
|
4 Participants
n=1 Participants
|
|
Region of Enrollment
United States
|
94 participants
n=58 Participants
|
94 participants
|
188 participants
n=1 Participants
|
PRIMARY outcome
Timeframe: up to 9 months (delivery)Incidence of gestational age of delivery less than 37 weeks
Outcome measures
| Measure |
Vaginal Progesterone
n=94 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=94 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Preterm Birth <37 Weeks
|
29 Participants
|
36 Participants
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Gestational age at delivery (weeks)
Outcome measures
| Measure |
Vaginal Progesterone
n=94 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=94 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Gestational Age of Delivery
|
37.36 weeks
Standard Deviation 2.72
|
36.34 weeks
Standard Deviation 4.1
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Delivery of pregnancy 20 0/7 - 33 6/7 weeks gestation
Outcome measures
| Measure |
Vaginal Progesterone
n=94 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=94 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Preterm Birth <34 Weeks
|
9 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: 2 monthsShort cervix diagnosis (transvaginal ultrasound cervical length \<=25mm prior to 24 weeks gestation
Outcome measures
| Measure |
Vaginal Progesterone
n=83 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=88 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Second Trimester Cervical Length <25mm
|
17 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Delivery mode- vaginal, cesarean, operative vaginal
Outcome measures
| Measure |
Vaginal Progesterone
n=94 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=94 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Mode of Delivery: Cesarean Section
|
20 Participants
|
29 Participants
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Maternal death for any reason from enrollment through hospital discharge from delivery hospitalization.
Outcome measures
| Measure |
Vaginal Progesterone
n=94 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=94 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Maternal Mortality
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)The Apgar score is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth. A score of 7, 8, or 9 is normal and is a sign that the newborn is in good health.
Outcome measures
| Measure |
Vaginal Progesterone
n=88 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=82 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
5 Minute Apgar Score<7
|
1 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Admission to neonatal intensive care unit for any reason (yes/no)
Outcome measures
| Measure |
Vaginal Progesterone
n=90 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=91 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Neonatal Intensive Care Unit Admission
|
31 Participants
|
25 Participants
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Population: Population analyzed limited to those with neonatal outcome data available regarding presence or absence of the composite findings.
Having at least one of the following: respiratory distress syndrome, grade III or IV intraventricular hemorrhage, culture proven sepsis, neonatal enterocolitis, or perinatal mortality up to 28 days of life
Outcome measures
| Measure |
Vaginal Progesterone
n=88 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=89 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Composite Neonatal Morbidity
Respiratory distress syndrome
|
8 Participants
|
8 Participants
|
|
Composite Neonatal Morbidity
Grade III or IV IVH
|
0 Participants
|
0 Participants
|
|
Composite Neonatal Morbidity
Sepsis
|
0 Participants
|
0 Participants
|
|
Composite Neonatal Morbidity
NEC
|
0 Participants
|
0 Participants
|
|
Composite Neonatal Morbidity
Perinatal mortality
|
0 Participants
|
3 Participants
|
|
Composite Neonatal Morbidity
None of the above
|
80 Participants
|
78 Participants
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Population: Population analyzed limited to those with neonatal outcome data available.
Birthweight assessed at delivery (grams)
Outcome measures
| Measure |
Vaginal Progesterone
n=90 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=91 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Birthweight
|
2940 grams
Standard Deviation 738
|
2793 grams
Standard Deviation 740
|
SECONDARY outcome
Timeframe: up to 10 months (4 weeks after delivery)In utero or neonatal death from enrollment through 28 days of neonatal life.
Outcome measures
| Measure |
Vaginal Progesterone
n=90 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=91 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Perinatal Mortality up to 28 Days of Life
|
0 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Medication side effects
Outcome measures
| Measure |
Vaginal Progesterone
n=91 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=81 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Medication Side Effects
Changes in mood
|
5 Participants
|
3 Participants
|
|
Medication Side Effects
No side effects
|
56 Participants
|
42 Participants
|
|
Medication Side Effects
Other
|
30 Participants
|
36 Participants
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Population: Participants analyzed limited to those who completed survey
5 point scale, 0 is very dissatisfied, 5 is very satisfied, 3 is neutral
Outcome measures
| Measure |
Vaginal Progesterone
n=86 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=78 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Satisfaction With Medication (5 Point Likert Scale)
|
3.77 units on a scale 1-5
Standard Deviation 1.18
|
4.06 units on a scale 1-5
Standard Deviation 1.0
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Vaginal progesterone: * Overall adherence: #days used/#days of treatment x 100 * Non-adherent: ≥4 days between doses Intramuscular progesterone: * Overall adherence: #weeks used/#weeks of treatment x 100 * Non-adherent: ≥10 days between doses
Outcome measures
| Measure |
Vaginal Progesterone
n=86 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=78 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Medication Adherence
|
82 percentage of doses taken
Standard Deviation 27
|
78 percentage of doses taken
Standard Deviation 35
|
SECONDARY outcome
Timeframe: up to 9 months (delivery)Population: Cerclage subgroup
Planned subgroup analysis for the primary outcome of patients with a cervical length \<25mm versus ≥25mm, history-indicated cerclage versus not, and for those started on progesterone 16-20 weeks versus 20-24 weeks.
Outcome measures
| Measure |
Vaginal Progesterone
n=22 Participants
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=21 Participants
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Planned Subgroup Analysis for the Outcome Preterm Birth <37 Weeks, <34 Weeks, <28 Weeks
|
8 Participants
|
11 Participants
|
Adverse Events
Vaginal Progesterone
Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths
Intramuscular Progesterone
Serious events: 0 serious events
Other events: 27 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Vaginal Progesterone
n=94 participants at risk
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Vaginal Progesterone
|
Intramuscular Progesterone
n=94 participants at risk
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
|
|---|---|---|
|
Product Issues
Early cessation
|
17.0%
16/94 • Number of events 16 • Until delivery
Serious adverse event was defined as an event likely related to medication assignment resulting in hospitalization, need for additional therapies to manage AE, or mortality
|
14.9%
14/94 • Number of events 14 • Until delivery
Serious adverse event was defined as an event likely related to medication assignment resulting in hospitalization, need for additional therapies to manage AE, or mortality
|
|
Product Issues
Medication cross over
|
8.5%
8/94 • Number of events 8 • Until delivery
Serious adverse event was defined as an event likely related to medication assignment resulting in hospitalization, need for additional therapies to manage AE, or mortality
|
13.8%
13/94 • Number of events 13 • Until delivery
Serious adverse event was defined as an event likely related to medication assignment resulting in hospitalization, need for additional therapies to manage AE, or mortality
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place