Canadian Study on the Association of Pessary With Progesterone

Study Overview
=================
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.

Official Title
-----------------
Canadian Study on the Association of Pessary With Progesterone

Conditions
-----------------
Preterm Birth, Short Cervix

Intervention / Treatment
-----------------
* Drug: Prometrium
* Device: Dr. Arabin, cerclage pessary perforated


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, controlled clinical trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravaginal progesterone<br>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.) | Drug: Prometrium<br>* Intravaginal use, off label, of Prometrium<br>* Other names: Progesterone;|
| Experimental: Intravaginal progesterone and pessary<br>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. | Drug: Prometrium<br>* Intravaginal use, off label, of Prometrium<br>* Other names: Progesterone;Device: Dr. Arabin, cerclage pessary perforated<br>* A Dr. Arabin, cerclage pessary perforated will be inserted participants diagnosed with a short cervix<br>* Other names: Pessary;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment feasibility | 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 | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Preterm birth, Short cervix, Pessary, Progesterone