PREGNANT Short Cervix Trial

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.

Study Overview

• Status: Completed
• Conditions: Preterm Delivery; Short Cervix; Short Uterine Cervical Length
• Intervention / Treatment: Drug: placebo; Drug: progesterone

Detailed Description

A Short uterine cervical length in the mid-trimester is the most powerful predictor of preterm birth.

• Study Type: Interventional
• Enrollment (Actual): 465
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Minsk, Belarus, 22004
    • 1st Clinical Hospital of the City of Minsk
  • Vitebsk, Belarus, 210009
    • Public Health Services Establishment "Vitebsk City Clinical Hospital of First Aid"
• Chile
  • Santiago, Chile
    • Escuela De Medicina, Pontificia Universidad Catolica De Chile
  • Santiago, Chile
    • Maternidad Hospital DR Sotero Del Rio
• Czech Republic
  • Prague, Czech Republic
    • Charles University & General Teaching Hospital
• India
  • Ahmedabad, India, 380008
    • Sheth L.G. Hospital
  • Andhra Pradesh, India, 5014
    • Mediciti Institute of Medical Sciences
  • Nagpur, India, 440003
    • Government Medical College
  • Maharashtra
    • Pune, Maharashtra, India, 411001
      • BJ Medical College & Sassoon Hospital
  • Tamil Nadu
    • Porur, Tamil Nadu, India, 600003
      • Sri Ramchandra Medical College and Research Institute
• Israel
  • Beer-Sheva, Israel, 84965
    • Soroka University Medical Center
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
  • Tel Hashomer, Israel, 58291
    • Sheba Medical Center
• Italy
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova Centro Prenatale Divisione di Ostetricia
• Russian Federation
  • Saint Petersburg, Russian Federation, 190000
    • Limited Liability Company "American Health Clinic"
  • Saint Petersburg, Russian Federation, 192174
    • Saint Petersburg State Healthcare Institution Maternity Hospital 17
• South Africa
  • Pretoria, South Africa, 0001
    • Steve Biko Academic Hospital Dept. of OB-GYN and Maternal Fetal Medicine
• Ukraine
  • Chernovtsy, Ukraine, 58001
    • Municipal health care establishment "City Maternity Clinical Hospital"
  • Dnepropetrovsk, Ukraine, 49000
    • Department of Obstetrics and Gynecology of Dnepropetrovsk State Medical Academy, Municipal establishment "City Maternity Hospital # 1"
  • Donetsk, Ukraine, 83062
    • M. Gorky Donetsk National Medical University, Department of Obstetrics, Gynecology and Perinatology, Maternity Hospital of 6th Central City Clinical Hospital
  • Kiev, Ukraine, 2175
    • Municipal clinical hospital #1
  • Kyiv, Ukraine, 01042
    • Antenatal Clinic # 1, Central Polyclinics of Pechersk District
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Dept. of OB/GYN
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Med Ctr Women's Care Center
  • California
    • Orange, California, United States, 92868
      • UCI Medical Center
    • Torrance, California, United States, 90502
      • Harbor-UCLA Medical Center
  • Florida
    • Miami, Florida, United States, 33101
      • University of Miami Leonard Miller School of Medicine Department of Obstetrics and Gynecology
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapi'olani Medical Center for Women and Children
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Perinatal Center of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Perinatal Diagnostic Center
  • Maryland
    • Baltimore, Maryland, United States, 21211
      • Johns Hopkins Community Physicians
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • Caritas St. Elizabeth's Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Perinatology Research Branch Hutzel Women's Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Healthcare System
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Research Department
    • Pontiac, Michigan, United States, 48341
      • St. Joseph Mercy-Oakland
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine, Dept. of OB/GYN
    • St. Louis, Missouri, United States, 63117
      • St. Louis University Health Sciences Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein Hospital
    • Mineola, New York, United States, 11501
      • Winthrop University Hosital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Lyndhurst Clinical Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-6130
      • UPHS Pennsylvania Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital OB/GYN / Maternal Fetal Medicine
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Regional Obstetrical Consultants, Chattanooga
    • Knoxville, Tennessee, United States, 37920
      • Regional Obstetrical Consultants, Knoxville
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Eastern Virginia Medical School
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Charleston Area Medical Center Clinical Trials Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

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
Placebo Comparator: Placebo; placebo vaginal gel	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
Active Comparator: Prochieve; Progesterone 8% Vaginal Gel	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; Other Names: Prochieve 8%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Birth <=32 6/7 Weeks Gestation.	9 to 13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Infants With Neonatal Morbidities Such as Respiratory Distress Syndrome (RDS), Bronchopulmonary Dysplasia (BPD), Intraventricular Hemorrhage (IVH), Proven Sepsis, and Necrotizing Enterocolitis (NEC)	Each infant is scored based on the 7 morbidity and mortality events above: 0= no morbidity event; 1 morbidity event; 2 morbidity events; 3 or more morbidity events; mortality	Delivery Hospitalization (1-212 days)
Number of Subjects With Preterm Birth at ≤27 6/7, ≤34 6/7, and <36 6/7 Weeks Gestation.	Number of participants at <=27 6/7 , <=34 6/7, and <36 6/7.	Gestational Age at Delivery
Number of Neonates Who Died.		Delivery to 28 days
Number of Infants With a Birth Weight < 1500 Grams or < 2500 Grams	Assessment of birth weight < 1500 grams or < 2500 grams	date of delivery

Collaborators and Investigators

• Sponsor: Juniper Pharmaceuticals, Inc.
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Director: George W. Creasy, MD, FACOG, Columbia Laboratories, Inc.; Study Director: Roberto Romero, MD, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Study Director: Sonia Hassan, MD, Wayne State University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Ultrasound Obstet Gynecol (2011)
• Open Access to Final Study Result Publication
• [Individual Patient Data Meta-analysis] 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

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: January 18, 2008
• First Submitted That Met QC Criteria: February 1, 2008
• First Posted (Estimate): February 14, 2008

Study Record Updates

• Last Update Posted (Estimate): March 13, 2012
• Last Update Submitted That Met QC Criteria: February 27, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Cervix; Preterm
• 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-1620-302; 09-CH-N014