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

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

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.

Study Overview

• Status: Completed
• Conditions: Preterm Labor
• Intervention / Treatment: Drug: micronized progesterone 400 mg (Utrogestan)

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 Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Ashdod, Israel
    • Assuta Ashdod Medical Center
  • North
    • Tiberias, North, Israel, 15208
      • Poriya Medical Center
  • Please Select
    • Afula, Please Select, Israel, 18100
      • Emek Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: HaEmek Medical Center, Israel

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2018
• Primary Completion (Actual): February 27, 2023
• Study Completion (Actual): February 27, 2023

Study Registration Dates

• First Submitted: April 20, 2015
• First Submitted That Met QC Criteria: April 29, 2015
• First Posted (Estimate): April 30, 2015

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 0080-13

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No