Vaginal Progesterone for Prevention of Preterm Birth After an Episode of Preterm Labor

Study Overview
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Brief Summary
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The investigators study objective is to investigate the effectiveness of vaginal micronized progesterone in prolonging pregnancy after an episode of preterm labor which responded to tocolytic treatment. Furthermore, the investigators aim is to study the mechanisms of actions of progesterone supplementation by examining its effect on the two components of parturition: cervical ripening and myometrial contractility. The investigators will utilize transvaginal ultrasound to assess the changes in the cervical tissue, and non-invasive trans-abdominal uterine EMG to assess the uterine muscle activity. The investigators will also look at the effect of progesterone on contraction frequency by tocodynamometer (TOCO), though EMG is expected to provide much more information.

Official Title
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Vaginal Progesterone for Prevention of Preterm Birth After an Episode of Preterm Labor

Conditions
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Preterm Birth

Intervention / Treatment
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* Drug: Progesterone
* Drug: placebo vaginal capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with singleton pregnancies at gestational ages 25+0 to 33+6 weeks after an episode of preterm labor, with cervical length ≤25mm: Patients presenting with signs and symptoms of preterm labor will be admitted and given the standard treatment for preterm labor, i.e. tocolysis for 48 hours, and antenatal steroids. Those who will remain undelivered for 48 hours and will be found to have a cervical length of 25mm or less will be offered entrance into the study. Preterm labor will be defined as at least 4 contractions in 30 minutes with cervical change assessed by digital cervical examination. Exclusion Criteria: Patients with preterm premature rupture of membranes (PPROM) will be excluded from the study, due to the possibility of ascending infection, as will those with suspected chorioamnionitis. We will not include multiple pregnancies. Patients with medical conditions that contraindicate tocolysis, such as non-reassuring fetal heart tracings, will also be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 48 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Experimental: Progesterone<br>Patients in this arm will receive two micronized progesterone capsules (Utrogestan® 200 mg, i.e. 400 mg of micronized progesterone in sunflower oil) placed into the posterior vaginal fornix once daily for up to 36+6 weeks of gestation. | Drug: Progesterone<br>* Two micronized progesterone capsules (Utrogestan® 200 mg, i.e. 400 mg of micronized progesterone in sunflower oil) placed into the posterior vaginal fornix once daily for up to 36+6 weeks of gestation.<br>* Other names: Brand name: Utrogestan® 200 mg;|
| Placebo Comparator: placebo<br>Patients will receive two placebo capsules placed into the posterior vaginal fornix once daily for up to 36+6 weeks of gestation. | Drug: placebo vaginal capsules<br>* Two placebo capsules placed (soy lecithin and sunflower oil) into the posterior vaginal fornix once daily for up to 36+6 weeks of gestation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preterm delivery (before completed 37th week of gestation) |  | Assessed every 14 days until delivery or 36+6 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in uterine electromyographic (EMG) activity | EMG tracing will be analyzed using power density spectrum (PDS) and raw signal amplitude techniques to find mean PDS peak frequency and magnitude. Propagation velocity (PV) of uterine EMG signals will be determined from the time interval between signal arrivals at adjacent electrodes. Amplitude and duration of EMG burst plots will also be analyzed. The study groups will be compared with the PDS, PV and EMG burst plots to determine if progesterone alters the EMG in a way that is less likely to proceed toward labor and delivery. | Assessed every 14 days until delivery or 36+6 weeks of gestation | 
| Cervical length changes | Cervical length will be measured by transvaginal ultrasound. The study groups will be compared to determine if progesterone alters the cervical shortening process. | Assessed every 14 days until delivery or 36+6 weeks of gestation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preterm birth, preterm labor, progesterone, uterine electromyography, cervical length