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

Phase 3

Completed

• Conditions: Preterm Delivery
• Interventions: Drug: dydrogesterone; Drug: Micronized progesterone

• Registration Number: NCT02989519
• Lead Sponsor: Sanpasitthiprasong Hospital

Brief Summary

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

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 Timeline

• Study Start: 2015-08
• Study First Submitted: 2016-12-07
• Study First Submitted QC: 2016-12-09
• Study First Posted: 2016-12-12
• Primary Completion: 2017-01-05
• Study Completion: 2017-03-01
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-07
• Last Update Posted: 2017-10-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 231

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
oral progesterone	dydrogesterone	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
vaginal progesterone	Micronized 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.

Primary Outcome Measures

Name	Time	Method
preterm delivery before 34 and 37 weeks	3 months

Secondary Outcome Measures

Name	Time	Method
change of cervical length	2 weeks

Trial Locations

Locations (1)

Piyawadee Wuttikonsammakit; 🇹🇭 Nai Muang, Ubon Ratchathani, Thailand