Clinical trial NCT01004029: Confirmatory Study of 17P vs Vehicle for Prevention of Preterm Birth in Women w/ Previous Spontaneous Preterm Delivery
Official title: A Phase 3B, Multi-Center, Randomized, Double-Blind Study of Hydroxyprogesterone Caproate (HPC) Injection, 250 mg/mL, Versus Vehicle for the Prevention of Preterm Birth in Women With a Previous Singleton Spontaneous Preterm Delivery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Preterm Birth
Keywords: 17P
17-HPC
17-OHPC
17-hydroxyprogesterone caproate
progestogens
preterm birth
recurrent preterm birth
spontaneous preterm birth
Lead sponsor: AMAG Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ResearchPoint Global
First posted: 2009-10-29
Enrollment: 1740
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

Each subject must meet the following criteria to be enrolled in this study:

1. Age ≥ 18 years.
2. Singleton gestation.
3. 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.
4. 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.

Exclusion Criteria:

1. Multifetal gestation.
2. 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.
3. 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.
4. Heparin therapy during current pregnancy or history of thromboembolic disease.
5. Maternal medical/obstetrical complications including:

   * Current or planned cerclage
   * Hypertension requiring medication
   * Seizure disorder
6. Subjects with a uterine anomaly (uterine didelphys or bicornate uterus). However, subjects with uterine fibroids are eligible for the study.
7. Unwillingness to comply with and complete the study.
8. A 14 weeks 0 days through 20 weeks 3 days of gestation ultrasound cannot be arranged before randomization.
9. Participation in an antenatal study in which the clinical status or intervention may influence gestational age at delivery.
10. 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.
11. Known hypersensitivity to hydroxyprogesterone caproate or its components.
12. 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.
13. 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.

Primary outcomes:
measure: Preterm Birth <35 Weeks Gestation
timeFrame: Up to 35 weeks
measure: Neonatal Composite Index (NCI)
timeFrame: Until 28 days of life or discharge from the neonatal intensive care unit (NICU), whichever occurred later.
Secondary outcomes:
measure: Fetal/Early Infant Death
timeFrame: 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).
measure: Preterm Birth Prior to 32 Weeks Gestation
timeFrame: Up to 32 weeks
measure: Preterm Birth Prior to 37 Weeks Gestation
timeFrame: Up to 37 weeks
measure: Stillbirths
timeFrame: 20 weeks gestation until term
measure: Neonatal Deaths With ≥24 Weeks Gestational Age
timeFrame: Until 28 days of life or discharge from the NICU whichever occurred later.
Other outcomes:
Locations:
city: Montgomery
country: United States
facility: Drug Research & Analysis Corporation
state: Alabama
city: Tucson
country: United States
facility: Tucson Medical Center (Watching Over Mothers and Babies Foundation)
state: Arizona
city: La Mesa
country: United States
facility: Grossmont Center for Clinical Research
state: California
city: San Diego
country: United States
facility: Naval Medical Center San Diego - Department of Obstetrics and Gynecology
state: California
city: West Hills
country: United States
facility: Womens Health Specialists
state: California
city: Colorado Springs
country: United States
facility: Women's Associates, P.C.
state: Colorado
city: Lakewood
country: United States
facility: Red Rocks OB/GYN - Physician's Research Options, LLC
state: Colorado
city: Boynton Beach
country: United States
facility: Visions Clinical Research
state: Florida
city: Lake Worth
country: United States
facility: Palm Beach Obstetrics & Gynecology, PA (Altus Research)
state: Florida
city: Pembroke Pines
country: United States
facility: Global OB/GYN Centers
state: Florida
city: Riverdale
country: United States
facility: New Millennium Obstetrics & Gynecology, LLc
state: Georgia
city: Honolulu
country: United States
facility: Tripler Army Medical Center
state: Hawaii
city: Boise
country: United States
facility: The Women's Clinic
state: Idaho
city: Idaho Falls
country: United States
facility: Rosemark Women Care Specialists
state: Idaho
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Louisville
country: United States
facility: Women's Care Physicians/Obstetrical Specialists, PLLC
state: Kentucky
city: Bel Air
country: United States
facility: Steven Z. Lenowitz, MD, LLC
state: Maryland
city: Grand Rapids
country: United States
facility: Female Pelvic Medicine and Urogynecology Institute of Michigan
state: Michigan
city: Saginaw
country: United States
facility: Saginaw Valley Medical Research Group, LLC
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Fort Bragg
country: United States
facility: Womack Army Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Triad Research Partners, LLC
state: North Carolina
city: Bismarck
country: United States
facility: Mid Dakota clinicl, PC Center for Women
state: North Dakota
city: Englewood
country: United States
facility: HWC Women's Research Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University School of Medicine
state: Pennsylvania
city: Columbia
country: United States
facility: SC Clinical Research Center, LLC
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System University Medical Group
state: South Carolina
city: Memphis
country: United States
facility: Women's Physician's Group, MPLLC
state: Tennessee
city: Dallas
country: United States
facility: Practice Research Organization, Inc.
state: Texas
city: Fort Hood
country: United States
facility: Carl R. Darnall Army Medical Center
state: Texas
city: Fort Sam Houston
country: United States
facility: San Antonio Military Medical Center
state: Texas
city: McAllen
country: United States
facility: Research Associates Rio Grande Valley
state: Texas
city: Layton
country: United States
facility: Tanner Clinic
state: Utah
city: Pleasant Grove
country: United States
facility: Mt. Timpanogos Women's Health Care
state: Utah
city: Sandy
country: United States
facility: Salt Lake Women's Center, P.C.
state: Utah
city: Portsmouth
country: United States
facility: Naval Medical Center - Portsmouth
state: Virginia
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Wheaton Franciscan Healthcare - St. Joseph Campus
state: Wisconsin
city: Blagoevgrad
country: Bulgaria
facility: MHAT "Blagoevgrad", Department of obstetrics and Gynecology
city: Russe
country: Bulgaria
facility: Medical center "Teodora", LTD
city: Silistra
country: Bulgaria
facility: MHAT "Silistra", Obstetrics and Gynecology Department
city: Sofia
country: Bulgaria
facility: "Medical institute of Interior ministry", Sofia city PLC, Department of Gynecology
city: Sofia
country: Bulgaria
facility: Medical Centre "Avicena" Ltd
city: Sofia
country: Bulgaria
facility: SHAT " Sheinovo ",PLS, Maternity Clinic
city: Calgary
country: Canada
facility: University of Calgary - Foothills Hospital
state: Alberta
city: North Vancouver
country: Canada
facility: Lion's Gate Hospital (University of BC)
state: British Columbia
city: Oshawa
country: Canada
facility: Glazier Medical Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital, General Campus
state: Ontario
city: Windsor
country: Canada
facility: Victory Reproductive Care
state: Ontario
city: Windsor
country: Canada
facility: J. Leung Obstetrics and Gynaecology
state: Ontario
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
state: Jihomoravsky KRAJ
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
state: Olomoucky KRAJ
city: Ceske Budejovice 7
country: Czechia
facility: Nemocnice Ceske Budejovice, a.s. Gynekologicko-pordnicka klinika
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove Porodnicka a gynekologicka klinika
city: Ostrava-Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava Porodnicko-gynekologicka klinika
city: Plzen-Lochotin
country: Czechia
facility: Fakultni nemocnice Pizen Gynekologicko-pordnicka klinika
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum, Szuleszeti es Nogyogyaszati Klinika
state: Hajdu-bihar
city: Budapest
country: Hungary
facility: Fovarosi Onkormanyzat Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet, Szuleszet - Nogyogyaszat
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz, Szuleszet-Nogyogyaszat
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun Megyei Onkormanyzat Korhaza, Svegedi Tudmanyegyetem Altalanos Orvostudomanyi kar Oktato Korhaza
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Oktato Korhaz Egeszsegugyi Szolgaltato Nonprofit Kft.
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem, Szuleszeti es Nogyogyaszati Klinika
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
city: Bolzano
country: Italy
facility: Azienda Ospedaliera di Bolzano Ospedale Generale Regionale di Bolzano
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia - Ospedale Santa Maria dell a Misericordia
city: Arkhangelsk
country: Russian Federation
facility: Northern State Medical University
city: Arkhangelsk
country: Russian Federation
facility: Northern State Medical University
city: Belgorod
country: Russian Federation
facility: Belgorod Regional Clinical Hospital of St.Ioasaf
city: Kazan
country: Russian Federation
facility: State Educational Institution of Higher Professional Education "Kazan State Medical University of RosZdrav"
city: Kemerovo
country: Russian Federation
facility: Kemerovo State Medical Academy
city: Krasnoyarsk
country: Russian Federation
facility: 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
city: Moscow
country: Russian Federation
facility: State Educational Institution of Higher Professional Education "People's Friendship University of Russia" Department of Obstetrics and Gynecology with Course Perinatology
city: Moscow
country: Russian Federation
facility: Russian National Research Medical University named after N.I. Pirogov
city: Novosibirsk
country: Russian Federation
facility: Municipal Healthcare Institution "Novosibirsk Municipal Perinatal Centre"
city: Rostov-on-Don
country: Russian Federation
facility: Rostov Medical State University
city: Saint Petersburg
country: Russian Federation
facility: Almazov Federal Heart, Blood and Endocrinology Centre
city: St. Petersburg
country: Russian Federation
facility: State Educational Institution of Higher Professional Education "St. Petersburg l.l Mechnikov State Medical Academy of RosZdrav" Department of Obstetrics, Gynecology and Perinatology
city: St. Petersburg
country: Russian Federation
facility: State Institution "D.O. Otto Scientific Institute for Obstetrics and Gynecology"
city: Tomsk
country: Russian Federation
facility: Regional Perinatal Center
city: Yaroslavl
country: Russian Federation
facility: State Healthcare Institution "Regional Maternity Hospital"
city: Yekaterinburg
country: Russian Federation
facility: Federal State Institution "Ural Research Institute of Maternity and Infancy Care of Rosmedtechnologies"
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario Materno Infantil de Canarias
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Zaragoza
country: Spain
facility: "Hospital Universitario Miguel Servet
city: Chernivtsi
country: Ukraine
facility: City Clinical Maternity Hospital #1
city: Donets'k
country: Ukraine
facility: Donets'k Regional Centre of Mother and Child Care
city: Ivano-Frankivs'k
country: Ukraine
facility: Ivano-Frankivs'k Regional Prenatal Center, department of pregnant pathology
city: Kyiv
country: Ukraine
facility: <<Institute of Pediatrics, Obstetrics and Gynecology of AMS Ukraine>> Department of Rehabilitation and Reproduktive function of Women
city: Kyiv
country: Ukraine
facility: Polyclinic #1, Obolon district of Kyiv, maternity welfare department
city: Kyiv
country: Ukraine
facility: Kyiv City Centre of Reproduction and perinatal medicine, obstetric department
city: Kyiv
country: Ukraine
facility: SI "Institute of pediatrics, obstetrics and gynecology of AMS of Ukraine". Department of extragenital pathology and postnatal rehabilitation
city: Odessa
country: Ukraine
facility: Municipal Institution "Maternity Hospital #1"
city: Ternopil
country: Ukraine
facility: Ternopil' Municipal Hospital # 2
city: Uzhgorod
country: Ukraine
facility: Uzhgorod Municipal prenatal Centre, maternity welfare department #2
city: Zaporizhzhya
country: Ukraine
facility: Clinical Maternity Hospital No 4
city: Zhaporizhzhya
country: Ukraine
facility: Department of Obstetrics and Gynecology of Zhaporizhzhya Medical Academy of Postgraduate Education on the Base of Healthcare Institution Maternity Hospital No 3
Study officials:
References:
citation: Blackwell SC, Gyamfi-Bannerman C, Biggio JR Jr, Chauhan SP, Hughes BL, Louis JM, Manuck TA, Miller HS, Das AF, Saade GR, Nielsen P, Baker J, Yuzko OM, Reznichenko GI, Reznichenko NY, Pekarev O, Tatarova N, Gudeman J, Birch R, Jozwiakowski MJ, Duncan M, Williams L, Krop J. 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial. Am J Perinatol. 2020 Jan;37(2):127-136. doi: 10.1055/s-0039-3400227. Epub 2019 Oct 25.