Vaginal Progesterone to Reduce the Risk of Another Preterm Birth

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

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.

Study Overview

• Status: Completed
• Conditions: Pregnancy
• Intervention / Treatment: Drug: 8% progesterone vaginal gel; Drug: Placebo Vaginal Gel

Detailed 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

• Study Type: Interventional
• Enrollment (Actual): 636
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Department of OBGYN
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Visions Clinical Research-Tucson
  • California
    • Colton, California, United States, 92324
      • Women's Health Department
    • San Diego, California, United States, 92123
      • SanDiego Perinatal Center
    • Torrance, California, United States, 90509
      • Harbor - UCLA Medical Center
  • Colorado
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Maternal Fetal Specialists
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60612
      • University of Illinois
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Central Baptist Hospital
    • Louisville, Kentucky, United States, 40207
      • Maternal Fetal Medicine Norton Suburban Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70815
      • Maternal Fetal Medicine &Woman's Health Research
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Center-Shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21211
      • Johns Hopkins Community Physicians
    • Silver Springs, Maryland, United States, 20910
      • Holy Cross Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Brighton, Massachusetts, United States, 02135
      • St. Elizabeth's Medical Center -MFM
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
    • St. Louis, Missouri, United States, 63021
      • St. Louis University
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
    • Livingston, New Jersey, United States, 07039
      • Department of OBGYN, St. Barnabas Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • New York, New York, United States, 10019
      • St. Luke's - Roosevelt Hospital
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Pitt County Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27103
      • Lyndhurst Gynecologic Associates
  • Ohio
    • Bedford, Ohio, United States, 44146
      • Ohio Permanente Medical Group
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44104-5034
      • MacDonald Clinical Trials Unit, University Hospitals of Cleveland
    • Toledo, Ohio, United States, 43606
      • The Toledo Hospital
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Medical Center
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Primary Women's Healthcare
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • University Medical Group, Dept of OB/GYN
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Regional Obstetrical Consultants
    • Memphis, Tennessee, United States, 38120
      • Gynecology & Obstetrics
  • Texas
    • Austin, Texas, United States, 78705
      • Womens Partner In Health
    • Dallas, Texas, United States, 75231
      • Health Central Women's Care
    • Houston, Texas, United States, 77054
      • Clinical Research Center of Houston
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center
    • Odessa, Texas, United States, 79763
      • Texas Tech Health Sciences Center - Odessa
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • EVMS Maternal-Fetal Medicine, Hofheimer Hall
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Progesterone 8% vaginal gel	Drug: 8% progesterone vaginal gel; Progesterone 8% Vaginal gel, once daily, maximum duration from 18 07 weeks gestation to 37 0/7 weeks gestation; Other Names: Crinone; Prochieve
Placebo Comparator: 2; Placebo Vaginal Gel	Drug: Placebo Vaginal Gel; Placebo vaginal gel, once daily, maximum duration from 18 07 weeks gestation to 37 0/7 weeks gestation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of delivery <=32 weeks	18 weeks gestation through delivery

Secondary Outcome Measures

Outcome Measure	Time Frame
Frequency of delivery preterm	18 weeks gestation through delivery
Response to tocolytic therapy	Onset of preterm labor through resolution or delivery
Number of infant hospital days from delivery to discharge	Delivery date through hospital discharge date of infant

Collaborators and Investigators

• Sponsor: Juniper Pharmaceuticals, Inc.
• Investigators: Study Director: George W Creasy, MD, VP Clinical Research; Columbia Laboratories, Inc

Publications and helpful links

General Publications

• 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. doi: 10.1067/mob.2003.41.
• 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, Calda P, Bsharat M, Creasy GW. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007 Oct;30(5):687-96. doi: 10.1002/uog.5158.
• 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, Calda P, Bsharat M, Creasy GW. 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. Ultrasound Obstet Gynecol. 2007 Oct;30(5):697-705. doi: 10.1002/uog.5159.
• O'Brien JM, Defranco EA, Adair CD, Lewis DF, Hall DR, How H, Bsharat M, Creasy GW; Progesterone Vaginal Gel Study Group. Effect of progesterone on cervical shortening in women at risk for preterm birth: secondary analysis from a multinational, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2009 Dec;34(6):653-9. doi: 10.1002/uog.7338.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: June 25, 2004
• First Submitted That Met QC Criteria: June 28, 2004
• First Posted (Estimate): June 29, 2004

Study Record Updates

• Last Update Posted (Estimate): August 19, 2010
• Last Update Submitted That Met QC Criteria: August 18, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Pregnancy,; prevention of preterm birth,; prevention of preterm labor,
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: COL-1620-300