Randomized Double-blind Controlled Trial of Use of Dydrogesterone in Threatened Miscarriage

A Randomized Double-blind Controlled Trial of Use of Dydrogesterone in Women With Threatened Miscarriage in the First Trimester

The aim of this study is to determine whether the dydrogesterone therapy is associated with reduction in miscarriage in women with first trimester threatened miscarriage. The hypothesis is that the dydrogesterone therapy will significantly reduce the risk of miscarriage in women with threatened miscarriage.

Study Overview

• Status: Completed
• Conditions: Pregnancy
• Intervention / Treatment: Drug: Placebo; Drug: Dydrogesterone

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Chai Wan, Hong Kong
    • Department of Obstetrics and Gynaecology, PYNEH
  • Hong Kong, Hong Kong
    • Department of Obstetrics & Gynaecology, Queen Mary Hospital
  • Mong Kok, Hong Kong
    • Department of Obstetrics & Gynaecology, Kwong Wah Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age of women from 18-40 years at the time of recruitment (not beyond 40th birthday)
• Absence of fever
• Gestation less than 12 completed weeks as defined by pelvic ultrasound
• Presence of intrauterine gestational sac(s) if an urine pregnancy test is first positive within past 2 weeks
• Presence of intrauterine fetus(es) with crown-rump length of <7mm and no fetal pulsation, or presence of intrauterine fetus(es) with positive fetal heart pulsation confirmed on pelvic scanning

Exclusion Criteria:

• Age of women >40 years at the time of recruitment
• History of recurrent miscarriage defined as at least three consecutive spontaneous miscarriages
• History of known parental chromosomal abnormalities
• Heavy vaginal bleeding requiring surgical intervention
• Severe abdominal pain requiring surgical intervention
• Absence of cardiac pulsation in a fetal pole with crown-rump length of >=7mm on transvaginal scanning
• Use of hCG or progesterone treatment for threatened miscarriage prior to recruitment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dydrogesterone; Patients allocated to the dydrogesterone group will receive oral dydrogesterone 40mg stat, followed by 10mg orally three times a day, and placebo will be used in the control group accordingly. Patients will be followed up with weekly pelvic ultrasound till 12 completed weeks of gestation or 1 week after the bleeding stopped, whichever is longer.	Drug: Dydrogesterone; Other Names: Duphaston
Placebo Comparator: Placebo pill; Patients allocated to the dydrogesterone group will receive oral dydrogesterone 40mg stat, followed by 10mg orally three times a day, and placebo will be used in the control group accordingly. Patients will be followed up with weekly pelvic ultrasound till 12 completed weeks of gestation or 1 week after the bleeding stopped, whichever is longer.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The chance of miscarriage before 20 weeks of gestation	At 20 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate		At the time of delivery, from 24 weeks of gestation till term gestation
The proportion of heavy vaginal bleeding or severe abdominal pain requiring surgical intervention (<20 weeks)		Before 20 weeks of gestation
The incidence of antepartum hemorrhage	Any vaginal bleeding during pregnancy from the 24th week gestational age to term	From 24 weeks of gestation till term
The incidence of placenta previa	Placenta is being inserted partially or wholly in the lower uterine segment and will be diagnosed by antenatal ultrasound at second and third trimesters	From 24 weeks of gestation till term
The incidence of pregnancy-induced hypertension	Any development of newly-onset hypertension (blood pressure persistently >=140/90mmHg on two occasions at least 4 hours apart) during pregnancy after 20 weeks gestation, labour or the puerperium in a previously normotensive non-proteinuric women	From 20 weeks of gestation till term
The incidence of intrauterine death	Fetus dies in uterus after 24 weeks gestation	After 24 weeks of gestation till term
The incidence of preterm labour	Any premature spontaneous delivery from 24 weeks to 36 weeks gestation	From 24 weeks to 36 weeks gestation
Low birth weight at term (grams)	Baby born with birth weight less than 2500g at or after 37 weeks gestation	After 37 weeks gestation

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Man Ka Diana Chan, MBBS(HK), Department of Obstetrics & Gynaecology, Queen Mary Hospital

Publications and helpful links

General Publications

• Chan DMK, Cheung KW, Ko JKY, Yung SSF, Lai SF, Lam MT, Ng DYT, Lee VCY, Li RHW, Ng EHY. Use of oral progestogen in women with threatened miscarriage in the first trimester: a randomized double-blind controlled trial. Hum Reprod. 2021 Feb 18;36(3):587-595. doi: 10.1093/humrep/deaa327.
• Chan DM, Cheung KW, Yung SS, Lee VC, Li RH, Ng EH. A randomized double-blind controlled trial of the use of dydrogesterone in women with threatened miscarriage in the first trimester: study protocol for a randomized controlled trial. Trials. 2016 Aug 17;17(1):408. doi: 10.1186/s13063-016-1509-8.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): May 31, 2018
• Study Completion (Actual): May 31, 2018

Study Registration Dates

• First Submitted: April 29, 2014
• First Submitted That Met QC Criteria: April 30, 2014
• First Posted (Estimate): May 1, 2014

Study Record Updates

• Last Update Posted (Actual): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 15, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Dydrogesterone; Threatened miscarriage
• Additional Relevant MeSH Terms: Pregnancy Complications; Abortion, Spontaneous; Abortion, Threatened; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Dydrogesterone
• Other Study ID Numbers: UW 13-292