Vaginal Progesterone for the Prolongation of Pregnancy After Arrested Pre-term Labor

Study Overview
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Brief Summary
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Patients diagnosed with arrested pre-term labor following tocolytics at 24-34 gestational weeks will be randomly allocated to receive either vaginal micronized progesterone 400 mg/day or no treatment.

Detailed Description
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Since progesterone derivatives are useful in preventing preterm labor in cases of risk factors or previous preterm labor, we hypothesize that they will also show efficacy in pregnancy prolongation in women whose preterm labor was arrested following tocolytic treatment. Patients diagnosed with arrested pre-term labor following tocolytics at 24-34 gestational weeks will be randomly allocated to receive either vaginal micronized progesterone 400 mg/day or no treatment. This study has the potential to find a treatment to prevent preterm labor and thus to reduce neonatal morbidity and mortality.

Official Title
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Vaginal Progesterone for the Prolongation of Pregnancy After Arrested Pre-term Labor - Randomized Double Blind Placebo Controlled Trial

Conditions
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Preterm Labor

Intervention / Treatment
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* Drug: micronized progesterone 400 mg (Utrogestan)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age Tocolytic treatment between 24+0 and 34+0 weeks Patient's consent to participate in this study 24 hours after tocolytic initiation and up to 3 days after finishing the tocolytic treatment Arrest of preterm labor Exclusion Criteria Contraindication to ongoing pregnancy including: Suspected amnionitis during testing for eligibility- evidence of active infection including temperature ≥ 38.0°C and uterine tenderness, foul-smelling vaginal discharge, maternal tachycardia of 120 beats per minute or greater, or sustained fetal tachycardia of 160 beats per minute or greater Evidence of significant placental abruption (contractions and significant bleeding from placental origin) Intrauterine fetal death diagnosed at the time of admission Major fetal malformation Known maternal allergy to progesterone Current use of progesterone at the time of admission Epilepsy Breast cancer PPROM (preterm premature rupture of membranes) during testing for eligibility Age below 18 years Known active liver disease (elevated liver enzymes at twice the upper normal limit according to medical history or blood test that were taking doring standard medical care) History of deep vein thrombosis Major active psychiatric disorders (major affective disorders and psychotic disorders) Uncontrolled chronic hypertension Heart failure Chronic renal failure Pre-gestational diabetes with known target organ damage History of spontaneous preterm delivery Previous tocolytic treatment during the current pregnancy

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: micronized progesterone 400 mg<br>participants receive vaginal micronized progesterone (Utrogestan- 200mg×2 PV(per vagina) per day) | Drug: micronized progesterone 400 mg (Utrogestan)<br>* participants receive vaginal micronized progesterone (Utrogestan- 200mg×2 PV(per vagina) per day)<br>* Other names: Utrogestan- 200mg×2 PV(per vagina) per day;|
| No Intervention: No treatment<br>No treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean number of days from enrollment to delivery |  | Up to 18 weeks | 
| The rate of preterm spontaneous delivery | defined as spontaneous labor or preterm delivery following induction/cesarean section due to preterm premature rupture of membranes prior to 37 weeks of gestation | Up to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days from recruitment to repeated preterm labor episode or preterm premature rupture of membranes, up to 37 weeks of gestation |  | Up to 13 weeks | 
| Pregnancy prolongation beyond one week |  | Up to 18 weeks | 
| Need for repeated acute tocolysis |  | Up to 13 weeks | 
| Number of hospitalizations and length of stay until 36.6 gestational weeks |  | Up to 13 weeks | 
| The rate of preterm spontaneous labor (defined as spontaneous labor or preterm premature rupture of membranes prior to 37 weeks of gestation) |  | Up to 13 weeks | 
| Admission to the NICU (neonatal intensive care unit) |  | From delivery and up to 28 days | 
| Length of NICU stay |  | From delivery and up to 3 months | 
| Length of neonate hospital stay |  | From delivery and up to 3 months | 
| Fetal/neonatal death |  | Around delivery | 
| Birth weight and the rate of small for gestational age neonates |  | Around delivery | 
| The rate of neonatal complications | including transient tachypnea, RDS (respiratory distress syndrome), bronchopulmonary dysplasia, ventilatory support, supplemental oxygen, IVH (intraventricular hemorrhage), NEC (necrotizing enterocolitis), PDA (patent ductus arteriosus), retinopathy, neonatal sepsis, and congenital abnormalities not previously identified (specifically genital abnormalities). | From delivery and up to 3 months | 
| The rate of chorioamnionitis and endometritis |  | around delivery and up to 1 week post-partum | 
| Adverse medication reactions |  | Up to 13 weeks | 
| Postpartum hemorrhage |  | From delivery and up to 1 week post-partum | 
| Revision of uterine and cervix and reasons for the procedure |  | During the 48 hours from delivery | 
| Urinary tract or vulvovaginal infection until 36.6 weeks |  | Up to 13 weeks |