Vaginal Progesterone to Reduce the Risk of Another Preterm Birth

Pregnancy Clinical Trial

Official title:

A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Efficacy, Safety, and Tolerability of 8% Progesterone Vaginal Gel in Preventing Preterm Delivery in Pregnant Women at Increased-Risk for Preterm Delivery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00086177
• Other study ID #: COL-1620-300
• Status: Completed
• Phase: Phase 3
• First received: June 25, 2004
• Last updated: August 18, 2010
• Start date: April 2004
• Est. completion date: March 2009

Study information

• Verified date: August 2010
• Source: Juniper Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIndia: Drugs Controller General of IndiaCzech Republic: Ethics CommitteeChile: Instituto de Salud Pública de ChileSouth Africa: National Health Research Ethics Council
• Study type: Interventional

Clinical Trial Summary

This research study is being conducted at over 12 pregnancy research centers in the US. The study will compare an investigational treatment with a placebo (a treatment without medication). Neither the investigators nor the patients in the trial will know which treatment has been assigned. All study medications will be given vaginally once a day. Treatment will begin before pregnancy week 23 and will continue until the end of pregnancy week 36.

Description:

Patients who participate are to have:

• A single baby pregnancy (no twins or triplets allowed)

• Patients will start treatment before pregnancy week 23

• Patients must have a previous preterm birth (a "preemie")

• Patients must be 18-45 years of age

Recruitment information / eligibility

• Status: Completed
• Enrollment: 636
• Est. completion date: March 2009
• Est. primary completion date: January 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. The subject has a history of a documented spontaneous singleton preterm delivery (hospital or clinic record, letter from healthcare provider, or birth certificate) from 20 0/7 to 35 0/7 weeks gestational age with the immediate preceding pregnancy or has a cervical length of 2.5 cm or less measured by transvaginal ultrasound with the current pregnancy. "Spontaneous preterm delivery" is a delivery (<35 weeks), either vaginal or cesarean, that is initiated by either preterm PROM followed by contractions or preterm labor initiated with in-tact membranes. A previous preterm delivery secondary to an incompetent cervix where a cerclage is considered for this pregnancy is not considered a preterm delivery (please see Exclusion Criteria No. 10). Subjects enrolled based on a history of preterm delivery may have had a pregnancy loss (or losses) at <20 0/7 weeks gestational age between the preceding preterm delivery and the current pregnancy.

2. The female subject is between 18 and 45 years of age at the time of screening.

3. The pregnancy has an estimated gestational age between 16 0/7 weeks and 22 6/7 weeks.

4. The subject speaks either English or a common local language.

5. 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.

6. 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 previous history of an adverse reaction to progesterone or any component present in Prochieve® 8% vaginal gel.

2. The subject has been treated with a progestogen within the previous 4 weeks.

3. 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).

4. The subject has active thrombophlebitis or a thromboembolic disorder, or a history of hormone-associated thrombophlebitis or thromboembolic disorders.

5. The subject has liver dysfunction or disease.

6. The subject has known or suspected malignancy of the breast or genital organs.

7. The subject is currently participating in another investigational study or has participated in an investigational drug study within one month prior to screening for this study.

8. The subject's current pregnancy is complicated by a major fetal anomaly or known chromosomal abnormality.

9. The subject has a uterine anatomic malformation (bicornuate uterus, septate uterus)

10. The subject has a multifetal gestation.

11. The subject has a cervical cerclage in place or has plans to have one placed during the current pregnancy.

12. The subject, in the judgment of the investigator, will be unable or unwilling to comply with study-related assessments and procedures.

13. 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.

14. The subject is HIV positive with a CD4 count of _<350 cells/mm3 and is receiving more than 1 medication to prevent the transfer of AIDS to the fetus.

15. The subject has placenta previa or a low-lying placenta. The subject will be considered for the study if she is not at risk for increased bleeding and has not been given any vaginal precautions.

16. The subject's qualifying preterm delivery was an indicated delivery without preterm labor (i.e. delivery performed for fetal distress, maternal eclampsia/preeclampsia, fetal death, or amnionitis in the absence of contractions).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Pregnancy

Intervention

Drug:
• 8% progesterone vaginal gel
Progesterone 8% Vaginal gel, once daily, maximum duration from 18 07 weeks gestation to 37 0/7 weeks gestation
• Placebo Vaginal Gel
Placebo vaginal gel, once daily, maximum duration from 18 07 weeks gestation to 37 0/7 weeks gestation

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Northside Maternal Fetal Specialists	Atlanta	Georgia
United States	Womens Partner In Health	Austin	Texas
United States	Johns Hopkins Community Physicians	Baltimore	Maryland
United States	Maternal Fetal Medicine &Woman's Health Research	Baton Rouge	Louisiana
United States	Ohio Permanente Medical Group	Bedford	Ohio
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	St. Elizabeth's Medical Center -MFM	Brighton	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	Cooper University Hospital	Camden	New Jersey
United States	Regional Obstetrical Consultants	Chattanooga	Tennessee
United States	University of Chicago	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	MacDonald Clinical Trials Unit, University Hospitals of Cleveland	Cleveland	Ohio
United States	Women's Health Department	Colton	California
United States	Health Central Women's Care	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Kaiser Permanente	Denver	Colorado
United States	Pitt County Memorial Hospital	Greenville	North Carolina
United States	University Medical Group, Dept of OB/GYN	Greenville	South Carolina
United States	Clinical Research Center of Houston	Houston	Texas
United States	Central Baptist Hospital	Lexington	Kentucky
United States	Department of OBGYN, St. Barnabas Medical Center	Livingston	New Jersey
United States	Maternal Fetal Medicine Norton Suburban Hospital	Louisville	Kentucky
United States	Texas Tech University Health Sciences Center	Lubbock	Texas
United States	Gynecology & Obstetrics	Memphis	Tennessee
United States	University of South Alabama Department of OBGYN	Mobile	Alabama
United States	West Virginia University	Morgantown	West Virginia
United States	St. Luke's - Roosevelt Hospital	New York	New York
United States	EVMS Maternal-Fetal Medicine, Hofheimer Hall	Norfolk	Virginia
United States	Texas Tech Health Sciences Center - Odessa	Odessa	Texas
United States	Temple University Medical Center	Philadelphia	Pennsylvania
United States	SanDiego Perinatal Center	San Diego	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Louisiana State University Health Sciences Center-Shreveport	Shreveport	Louisiana
United States	Holy Cross Hospital	Silver Springs	Maryland
United States	St. Louis University	St. Louis	Missouri
United States	Washington University	St. Louis	Missouri
United States	The Toledo Hospital	Toledo	Ohio
United States	Harbor - UCLA Medical Center	Torrance	California
United States	Visions Clinical Research-Tucson	Tucson	Arizona
United States	Abington Primary Women's Healthcare	Willow Grove	Pennsylvania
United States	Lyndhurst Gynecologic Associates	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Juniper Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (3)

da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003 Feb;188(2):419-24. — View Citation

DeFranco EA, O'Brien JM, Adair CD, Lewis DF, Hall DR, Fusey S, Soma-Pillay P, Porter K, How H, Schakis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Cal — View Citation

O'Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, Soma-Pillay P, Porter K, How H, Schackis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Ca — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of delivery <=32 weeks		18 weeks gestation through delivery	No
Secondary	Frequency of delivery preterm		18 weeks gestation through delivery	No
Secondary	Response to tocolytic therapy		Onset of preterm labor through resolution or delivery	No
Secondary	Number of infant hospital days from delivery to discharge		Delivery date through hospital discharge date of infant	No

External Links

•   Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.
•   Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial.