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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Premature Birth, Obstetric Labor, Premature

Intervention / Treatment
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* Drug: Micronized progesterone suppository


Participation Criteria
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Eligibility Criteria
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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: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Micronized progesterone suppository<br>Micronized progesterone suppository 200 mg vaginally daily until 36 6/7 weeks' gestation. | Drug: Micronized progesterone suppository<br> <br> |
| Placebo Comparator: Placebo suppository<br>One placebo suppository vaginally daily until 36 6/7 weeks' gestation. | Drug: Micronized progesterone suppository<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Delivered Before 37 Weeks' |  | Duration of current pregnancy, anticipated maximum 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Delivered Before 34 Weeks' | Evaluated in women enrolled prior to 32 weeks gestation | Duration of current pregnancy, anticipated maximum 18 weeks | 
| Delivery Within 2 Weeks of Randomization |  | 2 weeks | 
| Number of Weeks Pregnancy Prolongation |  | Duration of current pregnancy, anticipated maximum 18 weeks | 
| Infant Birth Weight |  | Day of delivery in current pregnancy | 
| Neonatal Intensive Care Unit Admission |  | Followed for duration of neonatal hospital stay, estimated maximum 16 weeks | 
| Number of Participants With Chorioamnionitis |  | Duration of current pregnancy, anticipated maximum 18 weeks | 
| 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. | Followed for duration of neonatal hospital stay, estimated maximum 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progesterone, Preterm