PREGNANT Short Cervix Trial

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to evaluate the usefulness of progesterone vaginal gel in decreasing the preterm birth rate in a population of pregnant women with short cervical length and at high risk for preterm birth.

Detailed Description
-----------------
A Short uterine cervical length in the mid-trimester is the most powerful predictor of preterm birth.

Official Title
-----------------
The Effect of Vaginal Progesterone Administration in the Prevention of Preterm Birth in Women With a Short Cervix [Vaginal Progesterone Bioadhesive Gel (Prochieve)® Extending Gestation A New Therapy for Short Cervix - Trial (PREGNANT Short Cervix - Trial)]

Conditions
-----------------
Preterm Delivery, Short Cervix, Short Uterine Cervical Length

Intervention / Treatment
-----------------
* Drug: progesterone
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject has a short cervical length by transvaginal ultrasound (TVU) defined as 10-20mm. In cases of dynamic cervix, the shortest observed/documented cervical length by TVU is to be used as the cervical length for inclusion purposes. Singleton gestation. The pregnancy has an estimated gestational age between 19 0/7 weeks and 23 6/7 weeks. Maternal age between 15 (or local age of majority/emancipation) and 45 years of age at the time of screening. An alternative age range can be accepted according to the standards and applicable regulations of the study centers. The subject speaks either English or a common local language. The subject has voluntarily signed the Informed Consent Form and associated forms after having the contents explained, and all her questions are answered to her satisfaction and understanding. In the opinion of the investigator, the subject is able to understand the study and is able to give informed consent, as well as participate in it and adhere to study procedures. Exclusion Criteria: The subject has a cervical length <10 or >20mm. The subject has a multifetal gestation. The subject has or is scheduled to have a cervical cerclage prior to randomization. According to ACOG Practice Bulletin Number 48 (November 2003), cerclage can be considered in a subject with a history of 3 or more unexplained midtrimester pregnancy losses or preterm deliveries.228,229 Subjects diagnosed to have acute cervical insufficiency with bulging membranes passing the external os. The subject has a previous history of an adverse reaction to progesterone or any component present in Prochieve® 8% vaginal gel. The subject has been treated with a progestogen within the previous 4 weeks. The subject is currently being treated for a seizure disorder, has an unstable psychiatric disorder, is taking antihypertensive therapy for chronic hypertension at the time of enrollment, has a history of congestive heart failure or chronic renal failure, or has uncontrolled diabetes mellitus (known end-organ dysfunction secondary to vascular disease). The subject has active thrombophlebitis or a thromboembolic disorder, or a history of hormone-associated thrombophlebitis or thromboembolic disorders. The subject has active liver dysfunction or disease. The subject has known or suspected malignancy of the breast or genital organs. The subject is currently participating in another interventional study or has participated in an interventional drug study within one month prior to screening for this study. The subject's current pregnancy is complicated by a major fetal anomaly or known chromosomal abnormality. The subject has a uterine anatomic malformation (bicornuate uterus, septate uterus) The subject, in the judgment of the investigator, will be unable or unwilling to comply with study-related assessments and procedures. The subject currently has preterm rupture of membranes, vaginal bleeding, known or suspected amnionitis, or signs or symptoms of preterm labor at the time of enrollment. The subject is HIV positive with a CD4 count of <350 cells/mm3 and is receiving more than one (1) medication to prevent the transfer of AIDS to the fetus. Complete placenta previa.

Ages Eligible for Study
-----------------
Minimum Age: 15 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo vaginal gel | Drug: placebo<br>* vaginal gel, 1.125 Grams once daily, beginning at 19 0/7 to 23 6/7 weeks gestation through 36 6/7 weeks gestation<br>|
| Active Comparator: Prochieve<br>Progesterone 8% Vaginal Gel | Drug: progesterone<br>* 8% vaginal gel, 1.125 Grams once daily, beginning at 19 0/7 to 23 6/7 weeks gestation through 36 6/7 weeks gestation<br>* Other names: Prochieve 8%;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Birth <=32 6/7 Weeks Gestation. |  | 9 to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Infants With Neonatal Morbidities Such as Respiratory Distress Syndrome (RDS), Bronchopulmonary Dysplasia (BPD), Intraventricular Hemorrhage (IVH), Proven Sepsis, and Necrotizing Enterocolitis (NEC) | Each infant is scored based on the 7 morbidity and mortality events above: 0= no morbidity event 1 morbidity event 2 morbidity events 3 or more morbidity events mortality | Delivery Hospitalization (1-212 days) | 
| Number of Subjects With Preterm Birth at ≤27 6/7, ≤34 6/7, and <36 6/7 Weeks Gestation. | Number of participants at <=27 6/7 , <=34 6/7, and <36 6/7. | Gestational Age at Delivery | 
| Number of Neonates Who Died. |  | Delivery to 28 days | 
| Number of Infants With a Birth Weight < 1500 Grams or < 2500 Grams | Assessment of birth weight < 1500 grams or < 2500 grams | date of delivery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Preterm, Cervix