Efficacy Study of a Cervical Pessary Containing Progesterone for the Prevention of Preterm Delivery

Study Overview
=================
Brief Summary
-----------------
Assess the efficacy of 2 Cervical Pessaries containing 6.3 g and 7.7 g micronized progesterone for the prevention of preterm delivery, established through spontaneous birth before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the pessary is inserted during weeks 16th and 24th and removed at 36 weeks and 6 days in pregnant women at high risk of premature birth.

Detailed Description
-----------------
Participant selection will be performed by screening the general population of pregnant women with single fetus monitored by the Hospital Healthcare Network, to investigate by serial transvaginal ultrasound performed between gestation weeks 16 (0 day to 7 days) and 24 (0 day to 7 days) those patients who have a cervical length between 10 mm and 25 mm, and/or women with a single fetus and cervical length ≥10 mm presenting one or more of the following risk factors: preterm birth prior to 35 (34 weeks and 6 days) weeks of gestation; premature rupture of membranes prior to 35 (34 and 6 days) weeks of gestation. After insertion of the pessary or beginning of the administration with vaginal progesterone capsules and until 28 weeks of gestation, participants in the 3 treatment groups will be monitored every 4 weeks at the most or more often, if the site has established so as a control standard. After 28 weeks, patients should be monitored every 2 weeks. The proportions of spontaneous preterm delivery before gestation weeks 32 and 34 will be compared between the control group and the 2 groups with the pessaries containing different doses of progesterone.

Official Title
-----------------
A Randomized, Open-Label, Controlled, Multi-Center Study on the Efficacy of a Sustained Release Progesterone Cerclage Cervical Pessary at Doses of 6.3 g or 7.7 g for the Prevention of Preterm Birth and a Maximum Duration of 20 Weeks.

Conditions
-----------------
Preterm Birth

Intervention / Treatment
-----------------
* Drug: Progesterone Cervical Pessary 6.3 g
* Drug: Progesterone 200 mg vaginal capsules
* Drug: Progesterone Cervical Pessary 7.7 g


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with a single pregnancy and a cervical length of 10 mm - 25 mm between 16 and 24 weeks of gestation, without any previous factors. Women with a single pregnancy with 10 mm or more cervical length between 16 and 24 weeks of gestation, and pre-existing risk factors risk factors for preterm birth: Previous preterm birth before week 35. Previous rupture of membranes before week 35 Exclusion Criteria: Pregnancies with: Major fetal abnormalities, such as lethal malformations or malformations requiring pre- or post-natal surgery; and fetal death before inclusion into the study. History of rupture of membranes or prophylactic cerclage before study entry. Cervical or vaginal injuries prior to insertion of the pessary (e.g., cervical erosion secondary to trauma, infection, or carcinoma; vesicovaginal or rectovaginal fistulas). Unconscious, severely ill or mentally disabled patients, or under 16 years of age. Patients for whom use of progesterone is contraindicated. Patients with history of thrombosis.

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

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

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

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Progesterone Cervical Pessary 6.3 g<br>90 pregnant women with Progesterone Cervical Pessary | Drug: Progesterone Cervical Pessary 6.3 g<br>* Progesterone Cervical Pessary low dose<br>|
| Experimental: Progesterone Cervical Pessary 7.7 g<br>90 pregnant women with Progesterone Cervical Pessary | Drug: Progesterone Cervical Pessary 7.7 g<br>* Progesterone Cervical Pessary high dose<br>|
| Active Comparator: Progesterone 200 mg vaginal capsules<br>90 pregnant women using Progesterone 200 mg vaginal capsules daily | Drug: Progesterone 200 mg vaginal capsules<br>* Progesterone 200 mg vaginal capsules daily<br>* Other names: Hormoral (Trade Mark) Capsules;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Not Giving Birth Before Week 32 and Week 34 of Gestation | To assess the efficacy of Cerclage Pessaries containing 6.3 g and 7.7 g micronized progesterone for the prevention of preterm delivery, established through spontaneous parturition before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the pessary is inserted between weeks 16 and 24 and removed at 36 weeks and 6 days in pregnant women at high risk of premature delivery. For the purpose of this analysis, pregnancies were no longer considered as high risk for the event if delivery occurred at week 34 of gestation and beyond. Gestational age was determined by the last menstruation date and were confirmed by measurement of the craniocaudal length obtained in the first trimester ultrasound, or by measurement of the cephalic circumference in the second trimester ultrasound predominating the actual date of the last menstrual period. The number of participants not giving birth before 32 weeks and 34 weeks are reported. | Up to 36 weeks of gestational age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Premature Rupture of Membranes | A participant with premature rupture of membrane typically recalls a sudden gush of fluid loss from the vagina, or steady loss of small amounts of fluid. Participants who reported vaginal discharge were examined by a physician. | Up to 36 weeks of gestational age | 
| Anatomical Feature: Length of the Uterine Cervix | During the pregnancy the length of the uterine cervix will be assessed. The rational is that premature birth is associated with uterine cervix shortening. The length of the cervix was determined using ultrasound examination. A positive change from baseline indicates a positive development, i.e. less likely to result in a preterm birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed. | Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age. | 
| Anatomical Feature: Position of the Uterine Cervix | During the pregnancy the position of the uterine cervix will be assessed. The rational being that premature birth is associated with uterine cervix positioning. The position of the cervix was determined using transvaginal ultrasound examination. In the change from baseline visit a positive value change indicated that the investigator believed that the position of the cervix changed in a positive manner to facilitate a term birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed. The results reported are the degrees of the cervix position relative to the longitudinal axis of the uterus. | Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age. | 
| Acceptability and Tolerance of Use of the Cerclage Pessary | A questionnaire was planned to be used to compare acceptability and tolerance in the insertion, during pregnancy and during the extraction of Cerclage Pessary. Data from this questionnaire was not collected. | Up to 36 weeks of gestational age | 
| Number of Adverse Events Related With the Use of Treatment | The number of adverse events reported were analyzed as being related with the treatment as well as for unexpectedness. | Up to 36 weeks of gestational age | 

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