Efficacy of Oral Progesterone and Vaginal Progesterone After Tocolytic Therapy in Threatened Preterm Labor

Comparison of the Efficacy of Oral Progesterone and Vaginal Progesterone After Tocolytic Therapy in Threatened Preterm Labor

The purpose of this study is to determine efficacy of vaginal and oral progesterone after tocolytic therapy in threatened preterm labor

Study Overview

• Status: Completed
• Conditions: Preterm Delivery
• Intervention / Treatment: Drug: dydrogesterone; Drug: Micronized progesterone

Detailed Description

A randomized controlled trial was conducted from August 2015 through December 2016. All pregnant women with single pregnancies of 28 to 33 weeks and 6 days who had been experienced for threatened or preterm labor with intact membrane as in inclusion criteria were approached and ask for enrollment. The gestational age of all patients was confirmed by antenatal record review and ultrasonographic confirmation. Threatened preterm labor was defined as the presence of regular uterine contractions without significant cervical changes as determined by digital pelvic examination. Preterm labor was defined as the simultaneous presence of regular uterine contractions and cervical changes, shortening and/or softening, or dilatation, as determined by digital pelvic examination. The women with preterm labor underwent standard tocolysis, which was administered for at least 48 hours, to allow corticosteroid promote fetal lung maturation. The patients who had proven membranes ruptured, and ultrasonographically found placenta previa, multiple pregnancy, fetal anomaly or aneuploidy would excluded. The participants had emergency condition that required for emergency delivery such as fetal distress, chorioamnionitis were also excluded. Participants were randomized into three groups which generated by computer programme to receive whether oral progesterone (dydrogesterone 10 mg; Duphaston™) per oral three times a day or vaginal progesterone (micronized progesterone 200 mg; Utrogestan™) or no progesterone (controlled group). All patients were digitally pelvic examined for evaluation of Bishop score and assessed cervical length by transvaginal ultrasound at enrollment and follow up visit at two weeks apart. Cervical length was measured by standard technique with a covered probe inserted into vagina after each woman had emptied her bladder. Excessive pressure on cervix was avoided. The mean value of 3 consecutive measurements was used for analysis. Informed consent and demographic data were obtained at the enrollment. Primary outcomes were preterm delivery before 34 and 37 weeks. Secondary outcomes include time until delivery (latency period,days), change of cervical length (cervical attenuation), maternal outcome, neonatal outcome, and side effects of drugs were collected. The main outcomes of preterm delivery, gestational age at parturition and birthweight were also collected by telephone call in case of out-side-hospital born or in case loss to follow up. Monitoring of all patients was evaluated every follow up visit for drug side effect, allergic response, and adverse events Statistical analysis Sample size was calculated according to the results of two studies by Dorota AgataBomba - Opon and Manju Choudhary which showed significant decreased preterm delivery <34 weeks (9.8% vs 35.3%,p=0.002) in vaginal progesterone group, and significant decreased preterm birth (33% vs 58% ; p= 0.034) in oral progesterone group. The sample size of 231 was used to evaluate the primary outcome of both drugs. Descriptive statistics were carried out using mean, median, standard deviation, interquartile range. Categorical data were tested for significance with the χ2tests. Continuous data were evaluated for normal distribution and tested for significance with ANOVA and Kruskal-Wallis test. Student t test and Man-Whitney U test were used to test significance between groups in case there is significant detection in ANOVA and Kruskal-Wallis test among groups. Statistical significance was defined as p<0.05.

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Ubon Ratchathani
    • Nai Muang, Ubon Ratchathani, Thailand, 34000
      • Piyawadee Wuttikonsammakit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Single pregnancies of 28 to 33 weeks and 6 days who had been experienced for threatened or preterm labor with intact membrane

Exclusion Criteria:

• Proven membranes ruptured
• Ultrasonographically found placenta previa, multiple pregnancy, fetal anomaly
• Aneuploidy detected.
• Had emergency condition that required for emergency delivery such as fetal distress, chorioamnionitis, prolapsed cord

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: no progesterone; All women with preterm labor underwent standard tocolysis, which was administered for at least 48 hours, to allow corticosteroid promote fetal lung maturation
Experimental: oral progesterone; All women with preterm labor underwent standard tocolysis, which was administered for at least 48 hours, to allow corticosteroid promote fetal lung maturation. All women in this arm received oral progesterone (dydrogesterone 10 mg; Duphaston™) per oral three times a day	Drug: dydrogesterone; Other Names: Duphaston
Experimental: vaginal progesterone; All women with preterm labor underwent standard tocolysis, which was administered for at least 48 hours, to allow corticosteroid promote fetal lung maturation. All women in this arm received vaginal progesterone (micronized progesterone 200 mg; Utrogestan™) at bed time.	Drug: Micronized progesterone; Other Names: Utrogestan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
preterm delivery before 34 and 37 weeks	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
change of cervical length	2 weeks

Collaborators and Investigators

• Sponsor: Sanpasitthiprasong Hospital
• Investigators: Principal Investigator: Piyawadee Wuttikonsammakit, MD, Instructor

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): January 5, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: December 7, 2016
• First Submitted That Met QC Criteria: December 9, 2016
• First Posted (Estimate): December 12, 2016

Study Record Updates

• Last Update Posted (Actual): October 10, 2017
• Last Update Submitted That Met QC Criteria: October 7, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: preterm labor; threatened preterm labor; progesterone efficacy
• 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: SPS2016-01

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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