Confirmatory Study of 17P vs Vehicle for Prevention of Preterm Birth in Women w/ Previous Spontaneous Preterm Delivery
- Conditions
- Preterm Birth
- Interventions
- Registration Number
- NCT01004029
- Lead Sponsor
- AMAG Pharmaceuticals, Inc.
- Brief Summary
As part of the continuing effort to study the benefit and risks of 17P and preterm delivery, this study is designed as a multi-center, randomized, double-blind, vehicle-controlled clinical trial of 17P for the prevention of preterm birth prior to 35 weeks, 0 days of gestation in women with a singleton pregnancy, aged 18 years or older, with a previous singleton spontaneous preterm delivery. The study also includes a population pharmacokinetic (PK) substudy to assess the hydroxyprogesterone caproate (HPC) exposure-response relationship and the effect of body mass index (BMI) on the PK of 17P.
- Detailed Description
One of the most significant risk factors for preterm birth is previous pregnancy history. Women who have had a prior preterm birth have a 2.5-fold greater risk than women with no prior history of preterm birth. Prophylactic methods for prevention of preterm birth, including tocolytic drugs, bed rest, and other interventions such as cerclage, have been shown in most studies to be ineffective. One of the preventive measures that has shown effectiveness in randomized trials is the use of progesterone agents.9,10 Progesterone has been shown to support gestation and to inhibit uterine activity.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 1740
Each subject must meet the following criteria to be enrolled in this study:
- Age ≥ 18 years.
- Singleton gestation.
- Project gestational age 16 weeks 0 days of gestation or more and less than or equal to 20 weeks 6 days of gestation at the time of randomization, based on clinical information and evaluation of the first ultrasound.
- Documented history of a previous singleton spontaneous preterm delivery. Spontaneous preterm birth is defined as delivery from 20 weeks 0 days to 36 weeks 6 days of gestation following spontaneous preterm labor or pPROM. Where possible, the gestational age of the previous preterm birth (referred to as the qualifying delivery) should be determined as described in "Gestational Age Determination". If the gestational age at delivery is obtained directly from the medical record and more than one gestational age appears, the latest will be used. As a validation of the gestational age of the previous delivery, if the infant weighed more than 3300 grams (the birth weight 90th percentile for 36 weeks gestational age), this will not qualify as preterm. The previous preterm delivery cannot be an antepartum stillbirth.
-
Multifetal gestation.
-
Known major fetal anomaly or fetal demise. An ultrasound examination between 14 weeks 0 days through 20 weeks 3 days of gestation must be performed to rule out fetal anomalies.
-
Progesterone treatment in any form (i.e., vaginal, oral, intramuscular) during current pregnancy, other than micronized progesterone delivered orally or vaginally provided it is stopped at least 4 weeks prior to the first dose of study medication.
-
Heparin therapy during current pregnancy or history of thromboembolic disease.
-
Maternal medical/obstetrical complications including:
- Current or planned cerclage
- Hypertension requiring medication
- Seizure disorder
-
Subjects with a uterine anomaly (uterine didelphys or bicornate uterus). However, subjects with uterine fibroids are eligible for the study.
-
Unwillingness to comply with and complete the study.
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A 14 weeks 0 days through 20 weeks 3 days of gestation ultrasound cannot be arranged before randomization.
-
Participation in an antenatal study in which the clinical status or intervention may influence gestational age at delivery.
-
Participation in this trial in a previous pregnancy. Women who were screened in a previous pregnancy, but not randomized, do not have to be excluded.
-
Known hypersensitivity to hydroxyprogesterone caproate or its components.
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Have any significant medical disorder that, in the opinion of the investigator, would be a contraindication to the use of the drug including those listed in section 5.3.2 of the investigational brochure. Other examples to consider include uncontrolled diabetes, known HIV infection or renal dysfunction.
-
Have any significant medical disorder that, in the opinion of the investigator, would preclude accurate evaluation of the subject's condition or outcome in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vehicle Vehicle Castor Oil Hydroxyprogesterone Caproate Injection (HPC), 250 mg/mL Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL HPC 250 mg/mL in oil
- Primary Outcome Measures
Name Time Method Preterm Birth <35 Weeks Gestation Up to 35 weeks Determine if treatment with 17P reduces the rate of preterm birth \< 35 weeks, 0 days of gestation in women with a previous singleton spontaneous preterm delivery.
Neonatal Composite Index (NCI) Until 28 days of life or discharge from the neonatal intensive care unit (NICU), whichever occurred later. The composite index is defined as a liveborn neonate with any of the following occurring at any time during the birth hospitalization up through discharge from the NICU: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis or proven sepsis.
- Secondary Outcome Measures
Name Time Method Fetal/Early Infant Death Delivery from 16 weeks 0 days through 19 weeks 6 days of gestation; or neonatal death occurring in liveborns born at less than 24 weeks gestation; or stillbirth (antepartum or intrapartum death) from 20 weeks gestation through term). Defined as spontaneous abortion/miscarriage (delivery from 16 weeks 0 days through 19 weeks 6 days of gestation) or neonatal death occurring in liveborns born at less than 24 weeks gestation or stillbirth (antepartum or intrapartum death from 20 weeks gestation through term), in the 17P group compared to the vehicle group
Preterm Birth Prior to 32 Weeks Gestation Up to 32 weeks Preterm Birth Prior to 37 Weeks Gestation Up to 37 weeks Stillbirths 20 weeks gestation until term Defined as all stillbirths/fetal deaths/in utero fetal losses occurring from 20 weeks gestation until term.
Neonatal Deaths With ≥24 Weeks Gestational Age Until 28 days of life or discharge from the NICU whichever occurred later. Neonatal death (from minutes after birth until 28 days of life) occurring in liveborns born at 24 weeks gestation or greater
Trial Locations
- Locations (103)
Medical Centre "Avicena" Ltd
🇧🇬Sofia, Bulgaria
Naval Medical Center San Diego - Department of Obstetrics and Gynecology
🇺🇸San Diego, California, United States
Global OB/GYN Centers
🇺🇸Pembroke Pines, Florida, United States
Victory Reproductive Care
🇨🇦Windsor, Ontario, Canada
J. Leung Obstetrics and Gynaecology
🇨🇦Windsor, Ontario, Canada
Drug Research & Analysis Corporation
🇺🇸Montgomery, Alabama, United States
Rosemark Women Care Specialists
🇺🇸Idaho Falls, Idaho, United States
HWC Women's Research Center
🇺🇸Englewood, Ohio, United States
SC Clinical Research Center, LLC
🇺🇸Columbia, South Carolina, United States
Female Pelvic Medicine and Urogynecology Institute of Michigan
🇺🇸Grand Rapids, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
"Medical institute of Interior ministry", Sofia city PLC, Department of Gynecology
🇧🇬Sofia, Bulgaria
Womack Army Medical Center
🇺🇸Fort Bragg, North Carolina, United States
Women's Physician's Group, MPLLC
🇺🇸Memphis, Tennessee, United States
Greenville Hospital System University Medical Group
🇺🇸Greenville, South Carolina, United States
University of Calgary - Foothills Hospital
🇨🇦Calgary, Alberta, Canada
Tanner Clinic
🇺🇸Layton, Utah, United States
MHAT "Blagoevgrad", Department of obstetrics and Gynecology
🇧🇬Blagoevgrad, Bulgaria
Medical center "Teodora", LTD
🇧🇬Russe, Bulgaria
MHAT "Silistra", Obstetrics and Gynecology Department
🇧🇬Silistra, Bulgaria
Carl R. Darnall Army Medical Center
🇺🇸Fort Hood, Texas, United States
Mt. Timpanogos Women's Health Care
🇺🇸Pleasant Grove, Utah, United States
Glazier Medical Centre
🇨🇦Oshawa, Ontario, Canada
Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
🇮🇹Bologna, Italy
Petz Aladar Megyei Oktato Korhaz, Szuleszet-Nogyogyaszat
🇭🇺Gyor, Hungary
Azienda Ospedaliera di Perugia - Ospedale Santa Maria dell a Misericordia
🇮🇹Perugia, Italy
Kemerovo State Medical Academy
🇷🇺Kemerovo, Russian Federation
Belgorod Regional Clinical Hospital of St.Ioasaf
🇷🇺Belgorod, Russian Federation
Lion's Gate Hospital (University of BC)
🇨🇦North Vancouver, British Columbia, Canada
Szegedi Tudomanyegyetem, Szuleszeti es Nogyogyaszati Klinika
🇭🇺Szeged, Hungary
Northern State Medical University
🇷🇺Arkhangelsk, Russian Federation
State Educational Institution of Higher Professional Education "People's Friendship University of Russia" Department of Obstetrics and Gynecology with Course Perinatology
🇷🇺Moscow, Russian Federation
Fovarosi Onkormanyzat Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet, Szuleszet - Nogyogyaszat
🇭🇺Budapest, Hungary
Fakultni nemocnice Ostrava Porodnicko-gynekologicka klinika
🇨🇿Ostrava-Poruba, Czechia
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Fakultni nemocnice Pizen Gynekologicko-pordnicka klinika
🇨🇿Plzen-Lochotin, Czechia
Regional Perinatal Center
🇷🇺Tomsk, Russian Federation
Hospital 12 de Octubre
🇪🇸Madrid, Spain
State Healthcare Institution "Regional Maternity Hospital"
🇷🇺Yaroslavl, Russian Federation
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Polyclinic #1, Obolon district of Kyiv, maternity welfare department
🇺🇦Kyiv, Ukraine
Rostov Medical State University
🇷🇺Rostov-on-Don, Russian Federation
Almazov Federal Heart, Blood and Endocrinology Centre
🇷🇺Saint Petersburg, Russian Federation
Federal State Institution "Ural Research Institute of Maternity and Infancy Care of Rosmedtechnologies"
🇷🇺Yekaterinburg, Russian Federation
Hospital Universitario Puerta del Mar
🇪🇸Cadiz, Spain
Salt Lake Women's Center, P.C.
🇺🇸Sandy, Utah, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Wheaton Franciscan Healthcare - St. Joseph Campus
🇺🇸Milwaukee, Wisconsin, United States
Fakultni nemocnice Hradec Kralove Porodnicka a gynekologicka klinika
🇨🇿Hradec Kralove, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Jihomoravsky KRAJ, Czechia
San Antonio Military Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Grossmont Center for Clinical Research
🇺🇸La Mesa, California, United States
Tucson Medical Center (Watching Over Mothers and Babies Foundation)
🇺🇸Tucson, Arizona, United States
Women's Associates, P.C.
🇺🇸Colorado Springs, Colorado, United States
Visions Clinical Research
🇺🇸Boynton Beach, Florida, United States
Womens Health Specialists
🇺🇸West Hills, California, United States
Red Rocks OB/GYN - Physician's Research Options, LLC
🇺🇸Lakewood, Colorado, United States
Palm Beach Obstetrics & Gynecology, PA (Altus Research)
🇺🇸Lake Worth, Florida, United States
New Millennium Obstetrics & Gynecology, LLc
🇺🇸Riverdale, Georgia, United States
The Women's Clinic
🇺🇸Boise, Idaho, United States
Saginaw Valley Medical Research Group, LLC
🇺🇸Saginaw, Michigan, United States
Steven Z. Lenowitz, MD, LLC
🇺🇸Bel Air, Maryland, United States
Mid Dakota clinicl, PC Center for Women
🇺🇸Bismarck, North Dakota, United States
Temple University School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Practice Research Organization, Inc.
🇺🇸Dallas, Texas, United States
Research Associates Rio Grande Valley
🇺🇸McAllen, Texas, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
Naval Medical Center - Portsmouth
🇺🇸Portsmouth, Virginia, United States
SHAT " Sheinovo ",PLS, Maternity Clinic
🇧🇬Sofia, Bulgaria
The Ottawa Hospital, General Campus
🇨🇦Ottawa, Ontario, Canada
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Olomoucky KRAJ, Czechia
Nemocnice Ceske Budejovice, a.s. Gynekologicko-pordnicka klinika
🇨🇿Ceske Budejovice 7, Czechia
Josa Andras Oktato Korhaz Egeszsegugyi Szolgaltato Nonprofit Kft.
🇭🇺Nyiregyhaza, Hungary
Bacs-Kiskun Megyei Onkormanyzat Korhaza, Svegedi Tudmanyegyetem Altalanos Orvostudomanyi kar Oktato Korhaza
🇭🇺Kecskemet, Hungary
Azienda Ospedaliera di Bolzano Ospedale Generale Regionale di Bolzano
🇮🇹Bolzano, Italy
State Educational Institution of Higher Professional Education "Krasnoyarsk State University named After Prof. V.F. Voino-Yasenetsky of Ministry of Health Russia" Department of Perinatology, Obstetrics and Gynecology of Medical Faculty
🇷🇺Krasnoyarsk, Russian Federation
Municipal Healthcare Institution "Novosibirsk Municipal Perinatal Centre"
🇷🇺Novosibirsk, Russian Federation
Russian National Research Medical University named after N.I. Pirogov
🇷🇺Moscow, Russian Federation
State Institution "D.O. Otto Scientific Institute for Obstetrics and Gynecology"
🇷🇺St. Petersburg, Russian Federation
State Educational Institution of Higher Professional Education "St. Petersburg l.l Mechnikov State Medical Academy of RosZdrav" Department of Obstetrics, Gynecology and Perinatology
🇷🇺St. Petersburg, Russian Federation
Hospital Universitario Materno Infantil de Canarias
🇪🇸Las Palmas De Gran Canaria, Spain
Hospital Virgen Del Rocio
🇪🇸Sevilla, Spain
Donets'k Regional Centre of Mother and Child Care
🇺🇦Donets'k, Ukraine
Hospital Universitario La Fe
🇪🇸Valencia, Spain
City Clinical Maternity Hospital #1
🇺🇦Chernivtsi, Ukraine
Ivano-Frankivs'k Regional Prenatal Center, department of pregnant pathology
🇺🇦Ivano-Frankivs'k, Ukraine
<<Institute of Pediatrics, Obstetrics and Gynecology of AMS Ukraine>> Department of Rehabilitation and Reproduktive function of Women
🇺🇦Kyiv, Ukraine
Kyiv City Centre of Reproduction and perinatal medicine, obstetric department
🇺🇦Kyiv, Ukraine
Clinical Maternity Hospital No 4
🇺🇦Zaporizhzhya, Ukraine
Municipal Institution "Maternity Hospital #1"
🇺🇦Odessa, Ukraine
Ternopil' Municipal Hospital # 2
🇺🇦Ternopil, Ukraine
Uzhgorod Municipal prenatal Centre, maternity welfare department #2
🇺🇦Uzhgorod, Ukraine
"Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
State Educational Institution of Higher Professional Education "Kazan State Medical University of RosZdrav"
🇷🇺Kazan, Russian Federation
Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum, Szuleszeti es Nogyogyaszati Klinika
🇭🇺Debrecen, Hajdu-bihar, Hungary
SI "Institute of pediatrics, obstetrics and gynecology of AMS of Ukraine". Department of extragenital pathology and postnatal rehabilitation
🇺🇦Kyiv, Ukraine
Department of Obstetrics and Gynecology of Zhaporizhzhya Medical Academy of Postgraduate Education on the Base of Healthcare Institution Maternity Hospital No 3
🇺🇦Zhaporizhzhya, Ukraine
Women's Care Physicians/Obstetrical Specialists, PLLC
🇺🇸Louisville, Kentucky, United States
Lyndhurst Clinical Research
🇺🇸Winston-Salem, North Carolina, United States
Tripler Army Medical Center
🇺🇸Honolulu, Hawaii, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Triad Research Partners, LLC
🇺🇸Winston-Salem, North Carolina, United States