PREGNANT Short Cervix Trial

Preterm Delivery Clinical 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)]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00615550
• Other study ID #: COL-1620-302
• Secondary ID: 09-CH-N014
• Status: Completed
• Phase: Phase 3
• First received: January 18, 2008
• Last updated: February 27, 2012
• Start date: March 2008
• Est. completion date: November 2010

Study information

• Verified date: February 2012
• Source: Juniper Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIndia: Drugs Controller General of IndiaIsrael: Ministry of HealthItaly: Ethics CommitteeChile: Instituto de Salud Pública de ChileRussia: Pharmacological Committee, Ministry of HealthUkraine: Ministry of HealthBelarus: Ministry of HealthSouth Africa: Medicines Control CouncilCzech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 465
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 15 Years to 45 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Premature Birth
• Preterm Delivery
• Short Cervix
• Short Uterine Cervical Length

Intervention

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
• 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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Juniper Pharmaceuticals, Inc.	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Belarus,  Chile,  Czech Republic,  India,  Israel,  Italy,  Russian Federation,  South Africa,  Ukraine, 

References & Publications (6)

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. — View 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. — View 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 — View 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. — View 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 m — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Birth <=32 6/7 Weeks Gestation.		9 to 13 weeks	No
Secondary	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)	No
Secondary	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	No
Secondary	Number of Neonates Who Died.		Delivery to 28 days	Yes
Secondary	Number of Infants With a Birth Weight < 1500 Grams or < 2500 Grams	Assessment of birth weight < 1500 grams or < 2500 grams	date of delivery	No

External Links

•   [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
•   [Trial Results] Progesterone vaginal gel for the reduction of recurrent preterm birth (free download)
•   Open Access to Final Study Result Publication
•   Prevention of sponatneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment. (free download)
•   Progesterone and the Risk of Preterm Birth among Women with a Short Cervix (free download)
•   Ultrasound Obstet Gynecol (2011)
•   Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix (free download)