Canadian Study on the Association of Pessary With Progesterone (CAPP)

April 5, 2023 updated by: Jean-Charles Pasquier, MD, PhD, Université de Sherbrooke
Prematurity is the leading cause of neonatal morbidity causing more than 1 million deaths worldwide per year. In 2012, a randomized controlled trial (RCT) testing "pessary" (silicone ring placed around the cervix) versus "no pessary" in patients with a short cervix showed a 4-fold reduction in the rate of spontaneous prematurity <34 weeks of gestation and a reduction in perinatal morbidity and mortality. This result was not found in a subsequent RCT and another study on the subject had to be stopped in the face of slow recruitment. Currently, the obstetric scientific community believes that other RCTs are needed before using the pessary in the clinic as a therapeutic option to prevent prematurity in the presence of a short cervix. However, before starting a large RCT, it is important to test the feasibility of recruitment.

Study Overview

Detailed Description

Hypothesis: A standardized recruitment process could allow the inclusion of 0.9% patient (CI 95%: 0,78-1.04) among women receiving a 18-23 weeks ultrasound scan.

Recruitment: Participants will be recruited, in a three-step manner, among women appointing for the 18-23 weeks ultrasound scan; i) assessment of the cervical length by abdominal ultrasound, ii) an endovaginal ultrasound measurement will be performed if the cervical length is ≤ 30 mm, iii) enrollment and consent of the patient to the pilot study, under the confirmation of the presence of a short cervix (≤ 25 mm) by the endovaginal ultrasound.

Intervention: Vaginal progesterone (200 mg/day, PROMETRIUM®, Merck Canada Inc.) until 37 weeks. Perforated cerclage pessaries (Dr. Arabin GmbH & Co. KG) will be placed in specialized clinic and will be removed at 37 weeks.

Size of the sampling and statistical analysis: This multicenter pilot study will be conducted in High-Risk Pregnancies Clinics in Quebec and in Ontario.

Over the 12 months period, the investigators expect to collect data from 26 000 abdominal ultrasounds. In accordance with the anticipated recruitment level of 0.9%, the investigators planned on enrolling 250 women. Within those women, 125 will be assigned randomly to the "progesterone" group and 125 to the "progesterone and pessary" group (1:1 ratio).

Perspective: This pilot study is designed to identify the challenges and provide strategies to deal with them in a larger study. Providing its feasibility, this study will lead to a definitive randomized controlled trial (including over 70 centers) to test the effectiveness of pessary and progesterone in preventing preterm birth.

Study Type

Interventional

Enrollment (Actual)

79

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Ontario
      • Kingston, Ontario, Canada
        • Kingston General Hospital
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital
    • Quebec
      • Montréal, Quebec, Canada, H2X 0C1
        • Centre Hospitalier de l'Universite de Montreal
      • Montréal, Quebec, Canada, H3T 1C5
        • CHU Sainte-Justine
      • Montréal, Quebec, Canada, H3T 1E2
        • CIUSSS du Centre Ouest-de-l'Île-de Montréal
      • Montréal, Quebec, Canada
        • St.Mary's Hospital Center
      • Quebec city, Quebec, Canada, G1V 4G2
        • CHU de Quebec-Universite Laval
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Universite de Sherbrooke

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • patient with a short cervix equal to or less than 25 mm by transvaginal ultrasound
  • gestational age between 18 (0/7) and 23 (6/7) weeks of gestation according to the results of the ultrasound of the first trimester, or by integrating the date of the last period
  • patients who were informed of the study and agreed to sign the consent form.

Exclusion Criteria:

  • pregnancy with a fetus with a major congenital malformation - regular and painful uterine activity - history of preterm premature rupture of membranes (PPROM) - active vaginal bleeding - complete and incomplete placenta previa - cerclage of the cervix in place - antecedent of conisation - multiple gestation - ballooning of membranes outside the cervix into the vagina - allergy/intolerance or hypersensitivity to progesterone or any of its ingredients - chronic medical conditions that would interfere with study participation or evaluation of treatment - vaginal administration of another drug.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intravaginal progesterone
Once the participant agrees and signs the consent form, the use of prophylactic progesterone will begin (PROMETRIUM, 200 mg in total of progesterone, 2 vaginal capsules per day at bedtime up to 36 6/7 weeks of gestation, Merck Canada Inc.)
Intravaginal use, off label, of Prometrium
Other Names:
  • Progesterone
Experimental: Intravaginal progesterone and pessary
Once the participant agrees and signs the consent form, the use of prophylactic progesterone will begin (PROMETRIUM, 200 mg in total of progesterone, 2 vaginal capsules per day at bedtime, Merck Canada Inc.). Also, a perforated pessary (Dr. Arabin, cerclage pessary perforated) will be inserted. The pessary will be removed and the progesterone treatment will be stopped at 36 6/7 weeks of gestation.
Intravaginal use, off label, of Prometrium
Other Names:
  • Progesterone
A Dr. Arabin, cerclage pessary perforated will be inserted participants diagnosed with a short cervix
Other Names:
  • Pessary

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recruitment feasibility
Time Frame: Up to 24 weeks (18 to 42 weeks of gestation)
According to the anticipated recruitment rate, 0.9% of women having an anatomy scan could be included (95% CI, 0.78- 1.04). We will determine the % of women included in the study (until the 42 week of gestation) over women that received a anatomy scan.
Up to 24 weeks (18 to 42 weeks of gestation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preterm delivery
Time Frame: Before 34 weeks
The secondary outcome is to determine the occurrence of spontaneous preterm births before 34 weeks in the progesterone alone group " without pessary harm ".
Before 34 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 4, 2018

Primary Completion (Actual)

October 6, 2022

Study Completion (Actual)

October 6, 2022

Study Registration Dates

First Submitted

July 12, 2017

First Submitted That Met QC Criteria

July 20, 2017

First Posted (Actual)

July 24, 2017

Study Record Updates

Last Update Posted (Actual)

April 6, 2023

Last Update Submitted That Met QC Criteria

April 5, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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