PREGNANT Short Cervix Trial

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)]”

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.

Intervention(s) in this Clinical Trial

• Drug: progesterone
  • 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
• Drug: placebo
  • vaginal gel, 1.125 Grams once daily, beginning at 19 0/7 to 23 6/7 weeks gestation through 36 6/7 weeks gestation

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Placebo
  • placebo vaginal gel
• Active Comparator: Prochieve
  • Progesterone 8% Vaginal Gel

Primary Measures

• Reduction in the frequency of preterm birth (less than or equal to 32 6/7 weeks gestation).
  • Time Frame: Gestational age at delivery
    Safety Issue?: No

Secondary Measures

• Reduction in the frequency of neonatal morbidities such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), proven sepsis, and necrotizing enterocolitis (NEC)
  • Time Frame: Delivery date to 28 days
    Safety Issue?: Yes
• Reduction in the frequency of preterm birth at ≤27 6/7, ≤34 6/7, and <36 6/7 weeks gestation
  • Time Frame: Gestational Age at Delivery
    Safety Issue?: No
• Reduction in the frequency of neonatal mortality
  • Time Frame: Delivery date to 28 days
    Safety Issue?: Yes
• Reduction in the frequency of admission for preterm labor
  • Time Frame: 20 0/7 weeks to 32 6/7 weeks gestation
    Safety Issue?: No
• Assessment of the admission-to-delivery interval in subjects receiving tocolytic therapy for preterm labor
  • Time Frame: 20 0/7 weeks to 32 6/7 weeks gestation
    Safety Issue?: No
• Assessment of Apgar scores, length, weight, and head circumference at birth, and incidence of congenital anomalies
  • Time Frame: date of delivery
    Safety Issue?: No
• Assessment of other indicators of neonatal morbidity such as admission to the NICU, the duration of stay in the NICU, and the total hospital stay
  • Time Frame: date of delivery to 28 days
    Safety Issue?: No

Inclusion Criteria:

• 1. 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.
• 2. Singleton gestation.
• 3. The pregnancy has an estimated gestational age between 19 0/7 weeks and 23 6/7 weeks.
• 4. 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.
• 5. The subject speaks either English or a common local language.
• 6. 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.
• 7. 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:

• 1. The subject has a cervical length <10 or >20mm.
• 2. The subject has a multifetal gestation.
• 3. 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
• 4. Subjects diagnosed to have acute cervical insufficiency with bulging membranes passing the external os.
• 5. The subject has a previous history of an adverse reaction to progesterone or any component present in Prochieve® 8% vaginal gel.
• 6. The subject has been treated with a progestogen within the previous 4 weeks.
• 7. 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).
• 8. The subject has active thrombophlebitis or a thromboembolic disorder, or a history of hormone-associated thrombophlebitis or thromboembolic disorders.
• 9. The subject has active liver dysfunction or disease.
• 10. The subject has known or suspected malignancy of the breast or genital organs.
• 11. 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.
• 12. The subject's current pregnancy is complicated by a major fetal anomaly or known chromosomal abnormality.
• 13. The subject has a uterine anatomic malformation (bicornuate uterus, septate uterus)
• 14. The subject, in the judgment of the investigator, will be unable or unwilling to comply with study-related assessments and procedures.
• 15. 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.
• 16. 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.
• 17. Complete placenta previa.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 15 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Columbia Laboratories Industry

Overall Clinical Trial Officials and Contacts

George W. Creasy, MD, FACOG Study Director Columbia Laboratories, Inc.  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00615550

Study ID Number: COL-1620-302

ClinicalTrials.gov Identifier: NCT00615550

Health Authority: United States: Food and Drug Administration

Progesterone vaginal gel for the reduction of recurrent preterm birth (free download)

Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix (free download)

Progesterone and the Risk of Preterm Birth among Women with a Short Cervix (free download)

Prevention of sponatneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment. (free download)

Ultrasound Obstet Gynecol (2011)