Randomized Controlled Trial of Vaginal Progesterone in Women With Threatened Preterm Labor (PROTO)

Pilot Randomized Controlled Trial of Vaginal Progesterone to Prevent Preterm Birth in Women With Threatened Preterm Labor

Prematurity remains the most important single factor in perinatal morbidity and mortality. Unfortunately, the rate of premature delivery is increasing in Canada and is especially high in Alberta with 7.5% of pregnancies ending before 37 weeks gestation. Despite years of research into the causes of spontaneous preterm labor, few effective treatments have been identified. Progesterone is one candidate treatment. The purpose of this study is to investigate whether progesterone can prolong pregnancy in women who have symptoms of preterm labor.

Pregnant women who have symptoms of premature labor will be invited to take part in the study if they are between 22 to 24 weeks pregnant. If they agree to join the study, they will be randomly allocated to either take progesterone 200mg each day via the vagina until 36 weeks, or to take a placebo preparation. Neither the women nor their clinician will know which group they are in.

Women and their babies will be followed until 28 days after the birth, to find out about the length of the pregnancy, any adverse events that might occur (none have been reported in previous trials), and to look at whether women have taken the treatment.

When the study is complete, the results for the progesterone group will be compared to the placebo group. If progesterone is found to be useful in helping to prolong pregnancy, then this will be a possible treatment to help mothers in the future.

Study Overview

• Status: Terminated
• Conditions: Obstetric Labor, Premature
• Intervention / Treatment: Drug: Vaginal progesterone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4J8
      • Foothills Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women with symptomatic premature contractions successfully arrested for at least 12 hours with tocolytics.
• Women with symptoms suggestive of early preterm labor whose contractions resolve without tocolysis but are fetal fibronectin positive.
• Gestational age 23(+0)-32(+6) weeks.
• Consent to taking part in the study.

Exclusion Criteria:

• Placenta previa
• Preterm premature rupture of membranes at presentation
• Pre-existing hypertension will be excluded in order to reduce the likelihood of iatrogenic preterm delivery within the study women
• Known major fetal anomaly detected on ultrasound
• Multiple pregnancy
• Maternal seizure disorder
• Active or history of thromboembolic disease
• Maternal liver disease
• Known or suspected breast malignancy or pathology
• Known or suspected progesterone-dependent neoplasia
• Plans to move to another city during pregnancy
• Previous participation in a progesterone trial during this pregnancy
• Known sensitivity to progesterone

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
Placebo Comparator: Placebo	Drug: Placebo; Capsules of placebo (sunflower oil). One capsule inserted vaginally per day from time of randomisation to gestational age 35(+6)weeks or delivery (if sooner).
Experimental: Vaginal progesterone	Drug: Vaginal progesterone; Capsules of 200mg micronised progesterone suspended in sunflower oil. One capsule inserted vaginally per day from time of randomisation to gestational age 35(+6)weeks or delivery (if sooner).; Other Names: Utrogestan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational age at birth	Gestational age at birth calculated from gestational age at pre-randomization baseline	At birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of women who have preterm birth <35 weeks		At birth
Proportion of women who have a preterm birth at <37 weeks		At birth
Maternal hospital length of stay (days)		Days from date of admission to date of discharge
Proportion of women who have hospital admission for premature labor		After birth
Maternal compliance with treatment	Diary self-report of treatment use	At time of birth
Neonatal hospital length of stay (days)		Days from birth to discharge from hospital
Neonatal morbidity	Respiratory distress syndrome (type 1), intraventricular hemorrhage, chronic lung disease, periventricular leukomalacia,necrotising eneterocolitis, retinopathy of prematurity	Up to 28 days after birth
Number of days of assisted ventilation (neonate)		Up to 28 days after birth
Number of days of supplemental oxygen (for neonate)		Up to 28 days after birth
Birth weight (grams)		At time of birth
Neonatal survival to discharge home (yes/no)		During 28 days after birth
Adverse events (maternal or neonate)		Up to 28 days after birth

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Stephen Wood, MD, MSc, University of Calgary

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: January 27, 2011
• First Submitted That Met QC Criteria: January 27, 2011
• First Posted (Estimate): January 31, 2011

Study Record Updates

• Last Update Posted (Estimate): January 8, 2015
• Last Update Submitted That Met QC Criteria: January 7, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Progesterone
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 21492