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TerminatedNCT01840228PALUpdated Jun 18, 2019Results posted

Vaginal Progesterone for the Prevention of Preterm Birth in Women With Arrested Preterm Labor

An interventional study of Micronized progesterone suppository in Premature Birth and Obstetric Labor, Premature, sponsored by Washington University School of Medicine. Terminated at 1 site in United States. Open to female participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-06-18.

Sponsored by Washington University School of Medicine · Not applicable, Interventional, and Prevention

Why this study was terminated
Low enrollment rate
Phase
Not applicable
Study type
Interventional
Enrollment
38
Allocation
Randomized
Ages
18 Years to 50 Years
Sex
Female
01

Study summary

Preterm birth, defined as birth before 37 weeks' gestation, is a leading cause of infant death and disease. Progesterone is the single most effective intervention in the prevention of preterm birth. However, current use of this therapy is limited to certain high-risk groups including women with a history of preterm birth and women with a short cervix. This study seeks to evaluate the efficacy of this preventive therapy in another high-risk group: women with arrested preterm labor. The investigators hypothesize that administration of vaginal progesterone in women who present with preterm labor but remain undelivered 12 hours after cessation of short-term therapy to inhibit contractions will result in lower rates of preterm birth before 37 weeks' than will administration of placebo.

Read the detailed description

RESEARCH DESIGN AND METHODS

The investigators will perform a randomized, blinded, placebo-controlled trial to evaluate the use of vaginal progesterone in women with arrested preterm labor after 24 weeks' gestation to reduce the risk of preterm birth before 37 weeks' gestation. Women enrolled in the study will be randomized to daily vaginal administration of progesterone (200 mg) or placebo from time of enrollment until 36 6/7 weeks' gestation. Women will be eligible if they have a singleton or twin gestation between 24 0/7 and 33 6/7 weeks' gestation and initially present with regular uterine contractions and a clinical diagnosis of preterm labor but remain undelivered without further cervical change 12 hours after discontinuation of acute tocolytic therapy. Women may also participate if it has been less than if they are considered eligible for discharge based on attending physician judgement prior to the 12 hour period of time.

Randomization and Blinding- Participants in the study will be randomized using a computer-generated randomization scheme with 1:1 allocation to receive progesterone or placebo. Investigators and research team members, participants, and the obstetric providers will be blinded to the allocated intervention.

Procedures-

  • Data collection- Information will be recorded from the participant's medical record. Additional study information not included in the medical record will be obtained directly from the participant in an interview with the research team member.
  • Follow-up- Regardless of whether the participant remains hospitalized or is discharged prior to delivery, she will meet with a study coordinator every 2 weeks. During the follow-up visit, a study team member will discuss compliance with the study drug and possible side effects. The participant will fill out a 1-page questionnaire that asks questions about compliance and side effects. This information will be recorded and provided to the Data Safety and Monitoring Board at the midpoint review.

SAMPLE SIZE ESTIMATION

The investigators plan to enroll 120 patients, with a 1:1 allocation to treatment and placebo. This sample size is adequate to detect a one-half reduction in the primary outcome, delivery before 37 weeks.

STATISTICAL ANALYSIS

Baseline characteristics of women randomized to progesterone will be compared with women randomized to placebo. Rates of delivery before 37 weeks' gestation will be compared among the groups using the Chi-square test. Secondary outcomes will be evaluated using the Chi-square test for binary outcomes and the Student t-test for continuous outcomes. Length of time from enrollment to delivery will be analyzed using Kaplan-Meier curves and the Cox proportional hazards model. All analyses will be performed using the intention-to-treat principle.

02

Conditions studied

  • Premature Birth
  • Obstetric Labor, Premature

Keywords

  • Preterm
  • Progesterone
03

In context

Premature Birth

2,554 studies on the registry are indexed under Premature Birth; 498 are open to participants now.

This study's enrollment of 38 is below the median of 84 across 1,688 interventional studies indexed under Premature Birth.

Browse Premature Birth studies →

Lead sponsor

Washington University School of Medicine is the lead sponsor of 1,765 studies on the registry; 271 are open to participants now.

Of its 324 completed or terminated interventional studies of FDA-regulated products, 212 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  • Singleton or twin gestation
  • Estimated gestational age between 24 0/7 and 33 6/7 weeks' gestation
  • Initially present with regular contractions and clinical diagnosis of preterm labor but remain undelivered with 1) no further cervical change 12 hours after discontinuation of acute tocolytic therapy; or 2) be considered eligible for discharge based on attending physician judgment prior to the 12 hour period of time
  • The participant's cervix must be at least 1 cm at the time of enrollment

Exclusion criteria

Exclusion Criteria:

  • Non-English speaking
  • Rupture of membranes
  • Chorioamnionitis
  • Non-reassuring fetal status
  • Maternal indication for delivery
  • Placental abruption
  • Intrauterine fetal demise
  • Prenatally diagnosed major fetal anomaly
  • Cervical cerclage in place
  • Previous administration of progesterone during the current pregnancy for a history of preterm birth or short cervix
  • Participant is either unwilling or unable to attend follow-up study visits following hospital discharge
05

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
38 participants (actual)

Study arms

  • Active comparator
    Micronized progesterone suppository

    Micronized progesterone suppository 200 mg vaginally daily until 36 6/7 weeks' gestation.

    Drug: Micronized progesterone suppository

  • Placebo comparator
    Placebo suppository

    One placebo suppository vaginally daily until 36 6/7 weeks' gestation.

    Drug: Micronized progesterone suppository

Interventions

  • DrugMicronized progesterone suppository
06

What researchers measure

Primary outcomes

  1. Number of Participants Who Delivered Before 37 Weeks'

    Time frame: Duration of current pregnancy, anticipated maximum 18 weeks

Secondary outcomes

  1. Number of Participants Who Delivered Before 34 Weeks'

    Evaluated in women enrolled prior to 32 weeks gestation

    Time frame: Duration of current pregnancy, anticipated maximum 18 weeks

  2. Delivery Within 2 Weeks of Randomization

    Time frame: 2 weeks

  3. Number of Weeks Pregnancy Prolongation

    Time frame: Duration of current pregnancy, anticipated maximum 18 weeks

  4. Infant Birth Weight

    Time frame: Day of delivery in current pregnancy

  5. Neonatal Intensive Care Unit Admission

    Time frame: Followed for duration of neonatal hospital stay, estimated maximum 16 weeks

  6. Number of Participants With Chorioamnionitis

    Time frame: Duration of current pregnancy, anticipated maximum 18 weeks

  7. Composite Neonatal Outcome

    A composite neonatal outcome comprising neonatal death, respiratory distress syndrome, bronchopulmonary dysplasia, severe (grade III/IV) interventricular hemorrhage, necrotizing enterocolitis, and sepsis.

    Time frame: Followed for duration of neonatal hospital stay, estimated maximum 16 weeks

07

Results

Posted Jun 18, 2019

Participant flow

Participant flow — Overall Study
MilestoneMicronized Progesterone SuppositoryPlacebo Suppository
Started1919
Completed1818
Not completed11
Withdrew: Lost to follow-up11

Outcome measures

PrimaryNumber of Participants Who Delivered Before 37 Weeks'
Time frame:
Duration of current pregnancy, anticipated maximum 18 weeks
Reported as:
Count of participants · Participants
Number of Participants Who Delivered Before 37 Weeks'
ParticipantsMicronized Progesterone SuppositoryPlacebo Suppository
Number of Participants Who Delivered Before 37 Weeks'1110
Statistical analysis
  • Micronized Progesterone Suppository vs Placebo Suppository · Chi-squared · p = 0.74 · Risk ratio (rr): 1.10 · 95% CI 0.63 to 1.91
SecondaryNumber of Participants Who Delivered Before 34 Weeks'

Evaluated in women enrolled prior to 32 weeks gestation

Time frame:
Duration of current pregnancy, anticipated maximum 18 weeks
Reported as:
Count of participants · Participants
Number of Participants Who Delivered Before 34 Weeks'
ParticipantsMicronized Progesterone SuppositoryPlacebo Suppository
Number of Participants Who Delivered Before 34 Weeks'36
Statistical analysis
  • Micronized Progesterone Suppository vs Placebo Suppository · Fisher Exact · p = 0.13 · Risk ratio (rr): 0.43 · 95% CI 0.14 to 1.36
SecondaryDelivery Within 2 Weeks of Randomization
Time frame:
2 weeks
Reported as:
Count of participants · Participants
Delivery Within 2 Weeks of Randomization
ParticipantsMicronized Progesterone SuppositoryPlacebo Suppository
Delivery Within 2 Weeks of Randomization64
Statistical analysis
  • Micronized Progesterone Suppository vs Placebo Suppository · Fisher Exact · p = 0.71 · Risk ratio (rr): 1.50 · 95% CI 0.51 to 4.43
SecondaryNumber of Weeks Pregnancy Prolongation
Time frame:
Duration of current pregnancy, anticipated maximum 18 weeks
Reported as:
Median · weeks
Number of Weeks Pregnancy Prolongation
weeksMicronized Progesterone SuppositoryPlacebo Suppository
Number of Weeks Pregnancy Prolongation5.3 (1.3 to 6.7)5.0 (2.0 to 8.0)
Statistical analysis
  • Micronized Progesterone Suppository vs Placebo Suppository · Wilcoxon (Mann-Whitney) · p = 0.73
SecondaryInfant Birth Weight
Time frame:
Day of delivery in current pregnancy
Reported as:
Mean · grams
Infant Birth Weight
gramsMicronized Progesterone Suppository - SINGLETONPlacebo Suppository - SINGLETONMicronized Progesterone Suppository - TWINSPlacebo Suppository - TWINS
Infant Birth Weight2454.9 ± 659.42523.1 ± 748.52164.4 ± 215.91974.1 ± 252.8
SecondaryNeonatal Intensive Care Unit Admission
Time frame:
Followed for duration of neonatal hospital stay, estimated maximum 16 weeks
Reported as:
Count of participants · Participants
Neonatal Intensive Care Unit Admission
ParticipantsMicronized Progesterone Suppository - SINGLETONPlacebo Suppository - SINGLETONMicronized Progesterone Suppository - TWINSPlacebo Suppository - TWINS
Neonatal Intensive Care Unit Admission2201
SecondaryNumber of Participants With Chorioamnionitis
Time frame:
Duration of current pregnancy, anticipated maximum 18 weeks
Reported as:
Count of participants · Participants
Number of Participants With Chorioamnionitis
ParticipantsMicronized Progesterone SuppositoryPlacebo Suppository
Number of Participants With Chorioamnionitis00
SecondaryComposite Neonatal Outcome

A composite neonatal outcome comprising neonatal death, respiratory distress syndrome, bronchopulmonary dysplasia, severe (grade III/IV) interventricular hemorrhage, necrotizing enterocolitis, and sepsis.

Time frame:
Followed for duration of neonatal hospital stay, estimated maximum 16 weeks
Reported as:
Count of participants · Participants
Composite Neonatal Outcome
ParticipantsMicronized Progesterone Suppository - SINGLETONPlacebo Suppository - SINGLETONMicronized Progesterone Suppository - TWINSPlacebo Suppository - TWINS
Composite Neonatal Outcome5537

Adverse events

Collected over Information about adverse events was collected from time of enrollment until discharge from the hospital after delivery for all participants, which is generally < 1 week after delivery. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Micronized Progesterone Suppository0/18 (0%)0/18 (0%)4/18 (22.2%)
Placebo Suppository0/18 (0%)0/18 (0%)5/18 (27.8%)
Most frequent other events
Most frequent other events
EventMicronized Progesterone SuppositoryPlacebo Suppository
Vaginal dischargeReproductive system and breast disorders3/185/18
Vaginal irritationReproductive system and breast disorders3/180/18
OtherGeneral disorders0/183/18

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Micronized Progesterone SuppositoryPlacebo SuppositoryTotal
<=18 years101
Between 18 and 65 years181937
>=65 years000
Age, Continuous
Age, Continuous(years)Micronized Progesterone SuppositoryPlacebo SuppositoryTotal
Mean25.8 ± 5.526.3 ± 4.626.0 ± 5.0
Sex: Female, Male
Sex: Female, Male(Participants)Micronized Progesterone SuppositoryPlacebo SuppositoryTotal
Female191938
Male000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Micronized Progesterone SuppositoryPlacebo SuppositoryTotal
American Indian or Alaska Native000
Asian213
Native Hawaiian or Other Pacific Islander000
Black or African American111021
White6713
More than one race000
Unknown or Not Reported011
Region of Enrollment
Region of Enrollment(participants)Micronized Progesterone SuppositoryPlacebo SuppositoryTotal
United States191938
Parity
Parity(births)Micronized Progesterone SuppositoryPlacebo SuppositoryTotal
Median1 (1 to 2)1 (1 to 2)1 (1 to 2)
Body mass index
Body mass index(kg/m2)Micronized Progesterone SuppositoryPlacebo SuppositoryTotal
Mean25.3 ± 7.925.4 ± 8.325.3 ± 8.0
Prior preterm birth
Prior preterm birth(Participants)Micronized Progesterone SuppositoryPlacebo SuppositoryTotal
Count of participants6814

8 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Washington University School of Medicine/ Barnes-Jewish Hospital
    Saint Louis, Missouri 63110, United States
09

References and documents

Publications

  • Lyell DJ, Pullen KM, Mannan J, Chitkara U, Druzin ML, Caughey AB, El-Sayed YY. Maintenance nifedipine tocolysis compared with placebo: a randomized controlled trial. Obstet Gynecol. 2008 Dec;112(6):1221-1226. doi: 10.1097/AOG.0b013e31818d8386. PubMed 19037029 ↗
  • Likis FE, Edwards DR, Andrews JC, Woodworth AL, Jerome RN, Fonnesbeck CJ, McKoy JN, Hartmann KE. Progestogens for preterm birth prevention: a systematic review and meta-analysis. Obstet Gynecol. 2012 Oct;120(4):897-907. doi: 10.1097/AOG.0b013e3182699a15. PubMed 22955308 ↗
  • Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, Vijayaraghavan J, Trivedi Y, Soma-Pillay P, Sambarey P, Dayal A, Potapov V, O'Brien J, Astakhov V, Yuzko O, Kinzler W, Dattel B, Sehdev H, Mazheika L, Manchulenko D, Gervasi MT, Sullivan L, Conde-Agudelo A, Phillips JA, Creasy GW; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31. doi: 10.1002/uog.9017. Epub 2011 Jun 15. PubMed 21472815 ↗
  • Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007 Aug 2;357(5):462-9. doi: 10.1056/NEJMoa067815. PubMed 17671254 ↗
  • Borna S, Sahabi N. Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial. Aust N Z J Obstet Gynaecol. 2008 Feb;48(1):58-63. doi: 10.1111/j.1479-828X.2007.00803.x. PubMed 18275573 ↗
  • Arikan I, Barut A, Harma M, Harma IM. Effect of progesterone as a tocolytic and in maintenance therapy during preterm labor. Gynecol Obstet Invest. 2011;72(4):269-73. doi: 10.1159/000328719. Epub 2011 Nov 12. PubMed 22086108 ↗

Study documents

  • Protocol and statistical analysis plan · Mar 11, 2015

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 18, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01840228
Lead sponsor
Washington University School of Medicine
Collaborators
Thrasher Research Fund
Responsible party
Sponsor
First posted
Apr 25, 2013
Start date
May 2013
Primary completion
May 7, 2018
Completion
May 7, 2018
Results posted
Jun 18, 2019
Last update
Jun 18, 2019

Study contacts

George A Macones, MD, MSCE
study chair · Washington University School of Medicine
Heather A Frey, MD, MSCI
principal investigator · Ohio State University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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