Different Types of Progesterone in the Prevention of Preterm Labor

Intramuscular 17Alpha-hydroxyprogestrone, Progesterone Suppositories and Dydrogesterone Tablets in Preventing Preterm Labor

Preterm birth is a common problem in obstetric care,with estimates ranging from 5% in several European countries to 18% in some African countries, Preterm labor defined as delivery before 37 completed weeks is the leading cause of perinatal and neonatal morbidity and mortality and strongly related to the developmental and neurological disabilities later in life..

There is still considerable uncertainty regarding the optimal progesterone type, route of administration, dosage and timing of start of therapy to prevent preterm labor in risky women

Study Overview

• Status: Unknown
• Conditions: Preterm Labor
• Intervention / Treatment: Drug: 17 alpha hydroxyprogestrone caproate; Drug: Vaginal progesterone; Drug: Oral dydrogesterone

Detailed Description

This study aims to compare between the efficacy of intramuscular 17alpha-hydroxyprogestrone, progesterone vaginal suppositories and dydrogesterone oral tablets in prevention of preterm labor in high risk women.

All women will be counseled regarding mode of intervention and informed consent will be obtained. All cases will be subjected to complete history taking, routine antenatal examination and investigations, treatment of genital or urinary tract infections if diagnosed. Routine obstetric ultrasound examination and measurement of cervical length by transvaginal ultrasound will be carried out at 16-18weeks of pregnancy.

The study population will be randomly distributed according to the mode of intervention into 3 groups.

Randomization is performed using a Computer-generated randomization system. Blinding of the intervention is not feasible in this trial (owing to the different route of administration of the studied drugs).Table of randomization is obtained

Group 1:

Women who will take intramuscular 17 alpha hydroxyprogestrone caproate

Dose:

250 mg intramuscularly, once weekly starting from 16 weeks till delivery or 36 weeks.

Group 2 :

Women who will take progesterone 200mg vaginal suppositories.

Dose:

Once per day starting from 16 weeks till delivery or 36 weeks

Group 3 :

Women who will take oral dydrogesterone

Dose:

Take 2 tablets a day starting from 16 weeks till delivery or 36 weeks

Color Doppler blood flow velocity examination of fetal circulation will be performed by an independent investigator blinded to treatment before treatment &after two weeks of treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Abbaseya
    • Cairo, Abbaseya, Egypt
      • Recruiting
      • Ain Shams Maternity Hospital
      • Contact: Mohamed Samy, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Singleton pregnancy
• Living fetus with gestational age 16-18weeks (calculated according to date of last menstrual period confirmed with earlier ultrasound examination).

• Presence of risk factor for preterm labor:

  1. Previous spontaneous preterm labor in previous singleton Pregnancy, OR
  2. Previous spontaneous second trimestric miscarriage less than 3 times, OR
  3. Short cervix less than 25mm diagnosed during midtrimesteric transvaginal ultrasound examination at 16-18 weeks with or without history of previous preterm labor.

Exclusion Criteria:

• Multiple pregnancy.
• Medical or obstetric conditions requiring termination of pregnancy

• Contraindication to progesterone administration or its use earlier in this pregnancy

  • Current or past history of thrombophlebitis, thromboembolic disorders, or cerebral apoplexy.
  • Liver dysfunction or disease.
  • Known or suspected malignancy of breast or genital organs.
  • Undiagnosed vaginal bleeding.
  • Missed abortion.
  • Known sensitivity to progesterone injection.
  • Known sensitivity to sesame oil/seeds.
• Congenital fetal anomalies
• Cervical cerclage in the current pregnancy.
• Presence of uterine anomalies (Unicornuate uterus , Uterus didelphys, bicornuate uterus,Septated uterus) or uterine fibroid.
• Presence of history of chronic hypertetion, chronic liver or kidney diseases, and pregnancy induced hypertension.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 17 alpha hydroxyprogestrone caproate Group; Patients will receive 250 mg of 17 alpha hydroxyprogestrone caproate intramuscularly once weekly starting from 16 weeks till delivery or 36 weeks.	Drug: 17 alpha hydroxyprogestrone caproate; 250 mg of 17 alpha hydroxyprogestrone caproate weekly
Active Comparator: Vaginal progesterone Group; Patients will receive vaginal progesterone 200 mg once per day starting from 16 weeks till delivery or 36 weeks.	Drug: Vaginal progesterone; 200 mg of vaginal progesterone daily
Active Comparator: Oral dydrogesterone Group; Patients will receive 2 tablets of oral dydrogesterone daily starting from 16 weeks till delivery or 36 weeks	Drug: Oral dydrogesterone; 2 tablets of dydrogesterone daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational age in weeks at delivery.	using either the last menstrual period in patients with regular cycles or early first trimester ultrasound to calculate the gestational age in weeks at delivery	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic changes in fetoplacental circulation	Measurement of U/S Doppler indices of umbilical artery and middle cerebral artery (namely PI, RI and S/D ratio) in fetal circulation	6 months
Unsatisfactory response	Number of patients who needed to increase the dose above the recommended initial dose.	6 months
Failure of prevention of preterm labor	Number of patients who suffered preterm labor and needed tocolysis	6 months
Birth weight	Birth weight in Kg	6 months
Neonatal APGAR score	Neonatal Apgar score at 1 and 5 min.	6 months
Need for NICU admission	Number of patients whose neonates were admitted to NICU Neonatal mortality.	6 months
Neonatal mortality	Number of neonatal deaths	6 months

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): August 1, 2018

Study Registration Dates

• First Submitted: April 25, 2016
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 25, 2018

Study Record Updates

• Last Update Posted (Actual): May 29, 2018
• Last Update Submitted That Met QC Criteria: May 24, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

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

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No