PREGNANT Short Cervix Trial

NCT00615550 | Completed Phase 3 Results DMC

• 2 other identifiers: COL-1620-30209-CH-N014
• Study Type: interventional
• Target: 465
• Locations: 10 countries
• Sites: 49

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.

Conditions

Preterm Delivery; Short Cervix; Short Uterine Cervical Length

Keywords

Preterm; Cervix

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Birth <=32 6/7 Weeks Gestation.

  9 to 13 weeks

Secondary Outcomes (4)

• Number of Infants With Neonatal Morbidities Such as Respiratory Distress Syndrome (RDS), Bronchopulmonary Dysplasia (BPD), Intraventricular Hemorrhage (IVH), Proven Sepsis, and Necrotizing Enterocolitis (NEC)

  Delivery Hospitalization (1-212 days)

• Number of Subjects With Preterm Birth at ≤27 6/7, ≤34 6/7, and <36 6/7 Weeks Gestation.

  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

  date of delivery

Study Arms (2)

Placebo

PLACEBO COMPARATOR

placebo vaginal gel

Drug: placebo

Prochieve

ACTIVE COMPARATOR

Progesterone 8% Vaginal Gel

Drug: progesterone

Interventions

progesterone DRUG

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

Also known as: Prochieve 8%

Prochieve

placebo DRUG

vaginal gel, 1.125 Grams once daily, beginning at 19 0/7 to 23 6/7 weeks gestation through 36 6/7 weeks gestation

Placebo

Eligibility Criteria

• Age: 15 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Singleton gestation.
• The pregnancy has an estimated gestational age between 19 0/7 weeks and 23 6/7 weeks.
• 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.
• The subject speaks either English or a common local language.
• 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.
• 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.

You may not qualify if:

• The subject has a cervical length \<10 or \>20mm.
• The subject has a multifetal gestation.
• 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
• Subjects diagnosed to have acute cervical insufficiency with bulging membranes passing the external os.
• The subject has a previous history of an adverse reaction to progesterone or any component present in Prochieve® 8% vaginal gel.
• The subject has been treated with a progestogen within the previous 4 weeks.
• 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).
• The subject has active thrombophlebitis or a thromboembolic disorder, or a history of hormone-associated thrombophlebitis or thromboembolic disorders.
• The subject has active liver dysfunction or disease.
• The subject has known or suspected malignancy of the breast or genital organs.
• 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.
• The subject's current pregnancy is complicated by a major fetal anomaly or known chromosomal abnormality.
• The subject has a uterine anatomic malformation (bicornuate uterus, septate uterus)
• The subject, in the judgment of the investigator, will be unable or unwilling to comply with study-related assessments and procedures.
• 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.

Sponsors & Collaborators

• Juniper Pharmaceuticals, Inc.: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (49)

University of South Alabama Dept. of OB/GYN

Mobile, Alabama, 36604, United States

Location

St. Joseph's Hospital and Med Ctr Women's Care Center

Phoenix, Arizona, 85013, United States

Location

UCI Medical Center

Orange, California, 92868, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Miami Leonard Miller School of Medicine Department of Obstetrics and Gynecology

Miami, Florida, 33101, United States

Location

Kapi'olani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Perinatal Center of Iowa

Des Moines, Iowa, 50314, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Perinatal Diagnostic Center

Lexington, Kentucky, 40503, United States

Location

Johns Hopkins Community Physicians

Baltimore, Maryland, 21211, United States

Location

Caritas St. Elizabeth's Medical Center

Boston, Massachusetts, 02135, United States

Location

Perinatology Research Branch Hutzel Women's Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Healthcare System

Detroit, Michigan, 48202, United States

Location

Spectrum Health Research Department

Grand Rapids, Michigan, 49503, United States

Location

St. Joseph Mercy-Oakland

Pontiac, Michigan, 48341, United States

Location

Washington University School of Medicine, Dept. of OB/GYN

St Louis, Missouri, 63110, United States

Location

St. Louis University Health Sciences Center

St Louis, Missouri, 63117, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Winthrop University Hosital

Mineola, New York, 11501, United States

Location

Albert Einstein Hospital

The Bronx, New York, 10461, United States

Location

Lyndhurst Clinical Research

Winston-Salem, North Carolina, 27103, United States

Location

UPHS Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107-6130, United States

Location

Thomas Jefferson University Hospital OB/GYN / Maternal Fetal Medicine

Philadelphia, Pennsylvania, 19107, United States

Location

Regional Obstetrical Consultants, Chattanooga

Chattanooga, Tennessee, 37403, United States

Location

Regional Obstetrical Consultants, Knoxville

Knoxville, Tennessee, 37920, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

Charleston Area Medical Center Clinical Trials Center

Charleston, West Virginia, 25304, United States

Location

1st Clinical Hospital of the City of Minsk

Minsk, 22004, Belarus

Location

Public Health Services Establishment "Vitebsk City Clinical Hospital of First Aid"

Vitebsk, 210009, Belarus

Location

Escuela De Medicina, Pontificia Universidad Catolica De Chile

Santiago, Chile

Location

Maternidad Hospital DR Sotero Del Rio

Santiago, Chile

Location

Charles University & General Teaching Hospital

Prague, Czechia

Location

BJ Medical College & Sassoon Hospital

Pune, Maharashtra, 411001, India

Location

Sri Ramchandra Medical College and Research Institute

Porur, Tamil Nadu, 600003, India

Location

Sheth L.G. Hospital

Ahmedabad, 380008, India

Location

MediCiti Institute of Medical Sciences

Andhra Pradesh, 5014, India

Location

Government Medical College

Nagpur, 440003, India

Location

Soroka University Medical Center

Beersheba, 84965, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Sheba Medical Center

Tel Litwinsky, 58291, Israel

Location

Azienda Ospedaliera di Padova Centro Prenatale Divisione di Ostetricia

Padua, 35128, Italy

Location

Limited Liability Company "American Health Clinic"

Saint Petersburg, 190000, Russia

Location

Saint Petersburg State Healthcare Institution Maternity Hospital 17

Saint Petersburg, 192174, Russia

Location

Steve Biko Academic Hospital Dept. of OB-GYN and Maternal Fetal Medicine

Pretoria, 0001, South Africa

Location

Municipal health care establishment "City Maternity Clinical Hospital"

Chernivtsi, 58001, Ukraine

Location

Department of Obstetrics and Gynecology of Dnepropetrovsk State Medical Academy, Municipal establishment "City Maternity Hospital # 1"

Dnipro, 49000, Ukraine

Location

M. Gorky Donetsk National Medical University, Department of Obstetrics, Gynecology and Perinatology, Maternity Hospital of 6th Central City Clinical Hospital

Donetsk, 83062, Ukraine

Location

Municipal clinical hospital #1

Kiev, 2175, Ukraine

Location

Antenatal Clinic # 1, Central Polyclinics of Pechersk District

Kyiv, 01042, Ukraine

Location

Related Publications (6)

• 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.

  PMID: 17899572 BACKGROUND

• 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.

  PMID: 17899571 BACKGROUND

• 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.

  PMID: 17671254 BACKGROUND

• 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.

  PMID: 17899585 BACKGROUND

• 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.

  PMID: 21472815 RESULT

• 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.

  PMID: 22284156 RESULT

Related Links

• Ultrasound Obstet Gynecol (2011)
• Open Access to Final Study Result Publication

MeSH Terms

Conditions

Premature Birth

Interventions

Progesterone

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Limitations and Caveats

Trial not powered for subgroup analysis.

Results Point of Contact

• Title: George W Creasy MD
• Organization: Columbia Laboratories

Gcreasy@columbialabs.com

973-486-8797

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2008
• First Posted: February 14, 2008
• Study Start: March 1, 2008
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: March 13, 2012
• Results First Posted: March 13, 2012

Record last verified: 2012-02

Locations

IL (3); RU (2); CL (2); US (27); CZ (1); IN (5); BE (2); ZA (1); IT (1); UA (5)