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

Phase 4

Completed

• Conditions: Preterm Labor
• Interventions: Drug: micronized progesterone 400 mg (Utrogestan)

• Registration Number: NCT02430233
• Lead Sponsor: HaEmek Medical Center, Israel

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-04-20
• Study First Submitted QC: 2015-04-29
• Study First Posted: 2015-04-30
• Study Start: 2018-12-19
• Status Verified: 2023-02
• Primary Completion: 2023-02-27
• Study Completion: 2023-02-27
• Last Update Submitted: 2023-02-27
• Last Update Posted: 2023-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 129

Inclusion Criteria

1. 18 years of age
2. Tocolytic treatment between 24+0 and 34+0 weeks
3. Patient's consent to participate in this study
4. 24 hours after tocolytic initiation and up to 3 days after finishing the tocolytic treatment
5. Arrest of preterm labor

Exclusion Criteria

1. Contraindication to ongoing pregnancy including:

   1. 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
   2. Evidence of significant placental abruption (contractions and significant bleeding from placental origin)
   3. Intrauterine fetal death diagnosed at the time of admission

2. Major fetal malformation

3. Known maternal allergy to progesterone

4. Current use of progesterone at the time of admission

5. Epilepsy

6. Breast cancer

7. PPROM (preterm premature rupture of membranes) during testing for eligibility

8. Age below 18 years

9. 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)

10. History of deep vein thrombosis

11. Major active psychiatric disorders (major affective disorders and psychotic disorders)

12. Uncontrolled chronic hypertension

13. Heart failure

14. Chronic renal failure

15. Pre-gestational diabetes with known target organ damage

16. History of spontaneous preterm delivery

17. Previous tocolytic treatment during the current pregnancy

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
micronized progesterone 400 mg	micronized progesterone 400 mg (Utrogestan)	participants receive vaginal micronized progesterone (Utrogestan- 200mg×2 PV(per vagina) per day)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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
Admission to the NICU (neonatal intensive care unit)	From delivery and up to 28 days
Fetal/neonatal death	Around delivery
Birth weight and the rate of small for gestational age neonates	Around delivery
The rate of chorioamnionitis and endometritis	around delivery and up to 1 week post-partum
Adverse medication reactions	Up to 13 weeks
Need for repeated acute tocolysis	Up to 13 weeks
Length of NICU stay	From delivery and up to 3 months
The rate of neonatal complications	From delivery and up to 3 months	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).
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
Length of neonate hospital stay	From delivery and up to 3 months
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

Trial Locations

Locations (3)

Poriya Medical Center; 🇮🇱 Tiberias, North, Israel

Emek Medical center; 🇮🇱 Afula, Please Select, Israel

Assuta Ashdod medical center; 🇮🇱 Ashdod, Israel