Clinical trial NCT00615550: 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)]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Preterm Delivery
Short Cervix
Short Uterine Cervical Length
Keywords: Preterm
Cervix
Lead sponsor: Juniper Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2008-02-14
Enrollment: 465
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Birth <=32 6/7 Weeks Gestation.
timeFrame: 9 to 13 weeks
Secondary outcomes:
measure: Number of Infants With Neonatal Morbidities Such as Respiratory Distress Syndrome (RDS), Bronchopulmonary Dysplasia (BPD), Intraventricular Hemorrhage (IVH), Proven Sepsis, and Necrotizing Enterocolitis (NEC)
timeFrame: Delivery Hospitalization (1-212 days)
measure: Number of Subjects With Preterm Birth at ≤27 6/7, ≤34 6/7, and <36 6/7 Weeks Gestation.
timeFrame: Gestational Age at Delivery
measure: Number of Neonates Who Died.
timeFrame: Delivery to 28 days
measure: Number of Infants With a Birth Weight < 1500 Grams or < 2500 Grams
timeFrame: date of delivery
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Dept. of OB/GYN
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Med Ctr Women's Care Center
state: Arizona
city: Orange
country: United States
facility: UCI Medical Center
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Miami
country: United States
facility: University of Miami Leonard Miller School of Medicine Department of Obstetrics and Gynecology
state: Florida
city: Honolulu
country: United States
facility: Kapi'olani Medical Center for Women and Children
state: Hawaii
city: Des Moines
country: United States
facility: Perinatal Center of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Perinatal Diagnostic Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Community Physicians
state: Maryland
city: Boston
country: United States
facility: Caritas St. Elizabeth's Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Perinatology Research Branch Hutzel Women's Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Healthcare System
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Research Department
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy-Oakland
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine, Dept. of OB/GYN
state: Missouri
city: St. Louis
country: United States
facility: St. Louis University Health Sciences Center
state: Missouri
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein Hospital
state: New York
city: Mineola
country: United States
facility: Winthrop University Hosital
state: New York
city: Winston-Salem
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Philadelphia
country: United States
facility: UPHS Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital OB/GYN / Maternal Fetal Medicine
state: Pennsylvania
city: Chattanooga
country: United States
facility: Regional Obstetrical Consultants, Chattanooga
state: Tennessee
city: Knoxville
country: United States
facility: Regional Obstetrical Consultants, Knoxville
state: Tennessee
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Charleston
country: United States
facility: Charleston Area Medical Center Clinical Trials Center
state: West Virginia
city: Minsk
country: Belarus
facility: 1st Clinical Hospital of the City of Minsk
city: Vitebsk
country: Belarus
facility: Public Health Services Establishment "Vitebsk City Clinical Hospital of First Aid"
city: Santiago
country: Chile
facility: Escuela De Medicina, Pontificia Universidad Catolica De Chile
city: Santiago
country: Chile
facility: Maternidad Hospital DR Sotero Del Rio
city: Prague
country: Czech Republic
facility: Charles University & General Teaching Hospital
city: Pune
country: India
facility: BJ Medical College & Sassoon Hospital
state: Maharashtra
city: Porur
country: India
facility: Sri Ramchandra Medical College and Research Institute
state: Tamil Nadu
city: Ahmedabad
country: India
facility: Sheth L.G. Hospital
city: Andhra Pradesh
country: India
facility: MediCiti Institute of Medical Sciences
city: Nagpur
country: India
facility: Government Medical College
city: Beer-Sheva
country: Israel
facility: Soroka University Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova Centro Prenatale Divisione di Ostetricia
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "American Health Clinic"
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Healthcare Institution Maternity Hospital 17
city: Pretoria
country: South Africa
facility: Steve Biko Academic Hospital Dept. of OB-GYN and Maternal Fetal Medicine
city: Chernovtsy
country: Ukraine
facility: Municipal health care establishment "City Maternity Clinical Hospital"
city: Dnepropetrovsk
country: Ukraine
facility: Department of Obstetrics and Gynecology of Dnepropetrovsk State Medical Academy, Municipal establishment "City Maternity Hospital # 1"
city: Donetsk
country: Ukraine
facility: M. Gorky Donetsk National Medical University, Department of Obstetrics, Gynecology and Perinatology, Maternity Hospital of 6th Central City Clinical Hospital
city: Kiev
country: Ukraine
facility: Municipal clinical hospital #1
city: Kyiv
country: Ukraine
facility: Antenatal Clinic # 1, Central Polyclinics of Pechersk District
Study officials:
affiliation: Columbia Laboratories, Inc.
name: George W. Creasy, MD, FACOG
role: STUDY_DIRECTOR
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Roberto Romero, MD
role: STUDY_DIRECTOR
affiliation: Wayne State University
name: Sonia Hassan, MD
role: STUDY_DIRECTOR
References:
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: Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007 Aug 2;357(5):462-9. doi: 10.1056/NEJMoa067815.
citation: Romero R. Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment. Ultrasound Obstet Gynecol. 2007 Oct;30(5):675-86. doi: 10.1002/uog.5174. No abstract available.
citation: Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, Vijayaraghavan J, Trivedi Y, Soma-Pillay P, Sambarey P, Dayal A, Potapov V, O'Brien J, Astakhov V, Yuzko O, Kinzler W, Dattel B, Sehdev H, Mazheika L, Manchulenko D, Gervasi MT, Sullivan L, Conde-Agudelo A, Phillips JA, Creasy GW; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31. doi: 10.1002/uog.9017. Epub 2011 Jun 15.
citation: Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Klein K, Rode L, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol. 2012 Feb;206(2):124.e1-19. doi: 10.1016/j.ajog.2011.12.003. Epub 2011 Dec 11.