Progesterone to Prevent Preterm Delivery

A Double Blinded Randomized Controlled Trial of Early Use of Oral Progesterone in All Women for Prevention of Preterm Delivery in Singleton Pregnancy (SINPRO Study)

Preterm birth (PTB) is a major challenge to perinatal health. It is defined as delivery before 37 completed gestational weeks. It accounts for 75% of perinatal deaths and more than 50% of long-term neurological disabilities, and it is the second most common cause of death in children under the age of 5 year. Neonates born preterm are at risk of respiratory distress syndrome, chronic lung disease, retinopathy of prematurity, necrotizing enterocolitis, intraventricular haemorrhage and sepsis in the short term, as well as cerebral palsy, motor and sensory impairment, learning difficulties, and increased risk of chronic disease in long run. It is estimated that the societal cost of PTB is $26 billion annually in the USA alone.

Until now, prevention or reduction of PTB is based on identification of risk factors in obstetrical history, biochemical markers and short cervix. History of PTB and asymptomatic short cervix at the second trimester are both strong predictors for PTB. In women with asymptomatic short cervix at the second trimester, vaginal progesterone could effectively reduce PTB. Universal cervical length screening followed by treatment with vaginal progesterone has been shown to be the most cost effective strategy in preventing PTB. These findings were confirmed in meta-analysis.

Nevertheless, only minority of women may benefit from progesterone treatment if it was being started at the second trimester. There is still a large proportion of PTB, which is currently not preventable, and the current approach to prevent PTB is far from ideal.

One possible hypothesis is that the initiation of progesterone treatment would be too late for its effect to take place. Therefore, we decide to use oral progesterone in the current study. The objective of the study is to determine whether early use of progesterone can prevent PTB better when compared with universal screening of cervical length and followed by treatment with progesterone in those with short cervix.

Study Overview

• Status: Unknown
• Conditions: Preterm Birth
• Intervention / Treatment: Drug: Dydrogesterone Oral Tablet; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Anticipated): 1714
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Hong Kong
    • Hong Kong, Hong Kong, China, 852
      • Recruiting
      • Department of Obstetrics and Gynaecology
      • Contact: Ka Wang Cheung; Phone Number: (852) 22553111; Email: kelvincheung82@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All women age ≥ 18 years old
• Confirmed intrauterine singleton pregnancy
• Gestational age less than 14 completed weeks as defined by pelvic ultrasound

Exclusion Criteria:

• Silent miscarriage: mean gestational sac diameter ≥25 mm without fetal pole, or embryo with crown rump length ≥7 mm and no heartbeat, or no interval growth
• Suspected ectopic pregnancy
• Multiple pregnancy with silent miscarriage of one twin
• Heavy vaginal bleeding requiring surgical intervention
• Severe abdominal pain requiring surgical intervention
• Presence of fever
• History of adverse reaction to progesterone
• History of breast or genital tract malignancy
• History of suspected thromboembolic disease
• Congenital uterine anomaly
• Unwillingness or inability to comply with study procedures
• Known paternal or maternal abnormal karyotype

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo group	Drug: Placebo Oral Tablet; Placebos will be prescribed from 12 - 36+6 weeks.
ACTIVE_COMPARATOR: Intervention group	Drug: Dydrogesterone Oral Tablet; Oral dysdrogesteone 10mg tds will be prescribed from 12 - 36+6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of preterm delivery	before 37+0 gestational weeks

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Publications and helpful links

General Publications

• Cheung KW, Seto MTY, Ng EHY. Early universal use of oral progesterone for prevention of preterm births in singleton pregnancy (SINPRO study): protocol of a multicenter, randomized, double-blind, placebo-controlled trial. Trials. 2020 Jan 30;21(1):121. doi: 10.1186/s13063-020-4067-z.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 15, 2019
• Primary Completion (ANTICIPATED): January 1, 2021
• Study Completion (ANTICIPATED): January 1, 2023

Study Registration Dates

• First Submitted: February 4, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (ACTUAL): February 12, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 10, 2019
• Last Update Submitted That Met QC Criteria: April 8, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Dydrogesterone
• Other Study ID Numbers: UW 17-308

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No