Clinical trial NCT00086177: Vaginal Progesterone to Reduce the Risk of Another Preterm Birth
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pregnancy
Keywords: Pregnancy,
prevention of preterm birth,
prevention of preterm labor,
Lead sponsor: Juniper Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2004-06-29
Enrollment: 636
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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

Eligibility criteria: 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).

Primary outcomes:
measure: Frequency of delivery <=32 weeks
timeFrame: 18 weeks gestation through delivery
Secondary outcomes:
measure: Frequency of delivery preterm
timeFrame: 18 weeks gestation through delivery
measure: Response to tocolytic therapy
timeFrame: Onset of preterm labor through resolution or delivery
measure: Number of infant hospital days from delivery to discharge
timeFrame: Delivery date through hospital discharge date of infant
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Department of OBGYN
state: Alabama
city: Tucson
country: United States
facility: Visions Clinical Research-Tucson
state: Arizona
city: Colton
country: United States
facility: Women's Health Department
state: California
city: San Diego
country: United States
facility: SanDiego Perinatal Center
state: California
city: Torrance
country: United States
facility: Harbor - UCLA Medical Center
state: California
city: Denver
country: United States
facility: Kaiser Permanente
state: Colorado
city: Atlanta
country: United States
facility: Northside Maternal Fetal Specialists
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Louisville
country: United States
facility: Maternal Fetal Medicine Norton Suburban Hospital
state: Kentucky
city: Baton Rouge
country: United States
facility: Maternal Fetal Medicine &Woman's Health Research
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center-Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Community Physicians
state: Maryland
city: Silver Springs
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Brighton
country: United States
facility: St. Elizabeth's Medical Center -MFM
state: Massachusetts
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Livingston
country: United States
facility: Department of OBGYN, St. Barnabas Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: St. Luke's - Roosevelt Hospital
state: New York
city: Greenville
country: United States
facility: Pitt County Memorial Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Lyndhurst Gynecologic Associates
state: North Carolina
city: Bedford
country: United States
facility: Ohio Permanente Medical Group
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: MacDonald Clinical Trials Unit, University Hospitals of Cleveland
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital
state: Ohio
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Medical Center
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Primary Women's Healthcare
state: Pennsylvania
city: Greenville
country: United States
facility: University Medical Group, Dept of OB/GYN
state: South Carolina
city: Chattanooga
country: United States
facility: Regional Obstetrical Consultants
state: Tennessee
city: Memphis
country: United States
facility: Gynecology & Obstetrics
state: Tennessee
city: Austin
country: United States
facility: Womens Partner In Health
state: Texas
city: Dallas
country: United States
facility: Health Central Women's Care
state: Texas
city: Houston
country: United States
facility: Clinical Research Center of Houston
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Odessa
country: United States
facility: Texas Tech Health Sciences Center - Odessa
state: Texas
city: Norfolk
country: United States
facility: EVMS Maternal-Fetal Medicine, Hofheimer Hall
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: VP Clinical Research; Columbia Laboratories, Inc
name: George W Creasy, MD
role: STUDY_DIRECTOR
References:
citation: 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.
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, 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.
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, 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.
citation: 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.