Clinical trial NCT03227705: Canadian Study on the Association of Pessary With Progesterone
Official title: Canadian Study on the Association of Pessary With Progesterone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Preterm Birth
Short Cervix
Keywords: Preterm birth
Short cervix
Pessary
Progesterone
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
Collaborators: name: Centre hospitalier de l'Université de Montréal (CHUM)
name: CHU de Quebec-Universite Laval
name: St. Justine's Hospital
name: Jewish General Hospital
name: The Ottawa Hospital
name: Queen's University
First posted: 2017-07-24
Enrollment: 79
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled clinical trial.
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recruitment feasibility
timeFrame: Up to 24 weeks (18 to 42 weeks of gestation)
Secondary outcomes:
measure: Preterm delivery
timeFrame: Before 34 weeks
Other outcomes:
Locations:
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Montréal
country: Canada
facility: CIUSSS du Centre Ouest-de-l'Île-de Montréal
state: Quebec
city: Montréal
country: Canada
facility: St.Mary's Hospital Center
state: Quebec
city: Quebec city
country: Canada
facility: CHU de Québec-Université Laval
state: Quebec
city: Sherbrooke
country: Canada
facility: Université de Sherbrooke
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: Jean-Charles Pasquier, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: