Confirmatory Study of 17P vs Vehicle for Prevention of Preterm Birth in Women w/ Previous Spontaneous Preterm Delivery

NCT ID: NCT01004029

Last Updated: 2022-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1740 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2018-10-31

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.

Conditions

Preterm Birth

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Vehicle

Castor Oil

Group Type: PLACEBO_COMPARATOR

Vehicle

Intervention Type: DRUG

Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.

Hydroxyprogesterone Caproate Injection (HPC), 250 mg/mL

HPC 250 mg/mL in oil

Group Type: ACTIVE_COMPARATOR

Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL

Intervention Type: DRUG

1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.

Interventions

Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL

1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.

Intervention Type: DRUG

Vehicle

Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.

Intervention Type: DRUG

Other Intervention Names

Makena; 17P; Placebo

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

ResearchPoint Global

OTHER

Sponsor Role: collaborator

AMAG Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Drug Research & Analysis Corporation

Montgomery, Alabama, United States

Tucson Medical Center (Watching Over Mothers and Babies Foundation)

Tucson, Arizona, United States

Grossmont Center for Clinical Research

La Mesa, California, United States

Naval Medical Center San Diego - Department of Obstetrics and Gynecology

San Diego, California, United States

Womens Health Specialists

West Hills, California, United States

Women's Associates, P.C.

Colorado Springs, Colorado, United States

Red Rocks OB/GYN - Physician's Research Options, LLC

Lakewood, Colorado, United States

Visions Clinical Research

Boynton Beach, Florida, United States

Palm Beach Obstetrics & Gynecology, PA (Altus Research)

Lake Worth, Florida, United States

Global OB/GYN Centers

Pembroke Pines, Florida, United States

New Millennium Obstetrics & Gynecology, LLc

Riverdale, Georgia, United States

Tripler Army Medical Center

Honolulu, Hawaii, United States

The Women's Clinic

Boise, Idaho, United States

Rosemark Women Care Specialists

Idaho Falls, Idaho, United States

University of Louisville

Louisville, Kentucky, United States

Women's Care Physicians/Obstetrical Specialists, PLLC

Louisville, Kentucky, United States

Steven Z. Lenowitz, MD, LLC

Bel Air, Maryland, United States

Female Pelvic Medicine and Urogynecology Institute of Michigan

Grand Rapids, Michigan, United States

Saginaw Valley Medical Research Group, LLC

Saginaw, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Duke University Medical Center

Durham, North Carolina, United States

Womack Army Medical Center

Fort Bragg, North Carolina, United States

Lyndhurst Clinical Research

Winston-Salem, North Carolina, United States

Triad Research Partners, LLC

Winston-Salem, North Carolina, United States

Mid Dakota clinicl, PC Center for Women

Bismarck, North Dakota, United States

HWC Women's Research Center

Englewood, Ohio, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Temple University School of Medicine

Philadelphia, Pennsylvania, United States

SC Clinical Research Center, LLC

Columbia, South Carolina, United States

Greenville Hospital System University Medical Group

Greenville, South Carolina, United States

Women's Physician's Group, MPLLC

Memphis, Tennessee, United States

Practice Research Organization, Inc.

Dallas, Texas, United States

Carl R. Darnall Army Medical Center

Fort Hood, Texas, United States

San Antonio Military Medical Center

Fort Sam Houston, Texas, United States

Research Associates Rio Grande Valley

McAllen, Texas, United States

Tanner Clinic

Layton, Utah, United States

Mt. Timpanogos Women's Health Care

Pleasant Grove, Utah, United States

Salt Lake Women's Center, P.C.

Sandy City, Utah, United States

Naval Medical Center - Portsmouth

Portsmouth, Virginia, United States

Madigan Army Medical Center

Tacoma, Washington, United States

Wheaton Franciscan Healthcare - St. Joseph Campus

Milwaukee, Wisconsin, United States

MHAT "Blagoevgrad", Department of obstetrics and Gynecology

Blagoevgrad, , Bulgaria

Medical center "Teodora", LTD

Rousse, , Bulgaria

MHAT "Silistra", Obstetrics and Gynecology Department

Silistra, , Bulgaria

"Medical institute of Interior ministry", Sofia city PLC, Department of Gynecology

Sofia, , Bulgaria

Medical Centre "Avicena" Ltd

Sofia, , Bulgaria

SHAT " Sheinovo ",PLS, Maternity Clinic

Sofia, , Bulgaria

University of Calgary - Foothills Hospital

Calgary, Alberta, Canada

Lion's Gate Hospital (University of BC)

North Vancouver, British Columbia, Canada

Glazier Medical Centre

Oshawa, Ontario, Canada

The Ottawa Hospital, General Campus

Ottawa, Ontario, Canada

Victory Reproductive Care

Windsor, Ontario, Canada

J. Leung Obstetrics and Gynaecology

Windsor, Ontario, Canada

Fakultni nemocnice Olomouc

Olomouc, Olomoucký kraj, Czechia

Fakultni nemocnice Brno

Brno, South Moravian, Czechia

Nemocnice Ceske Budejovice, a.s. Gynekologicko-pordnicka klinika

České Budějovice, , Czechia

Fakultni nemocnice Hradec Kralove Porodnicka a gynekologicka klinika

Hradec Králové, , Czechia

Fakultni nemocnice Ostrava Porodnicko-gynekologicka klinika

Ostrava-Poruba, , Czechia

Fakultni nemocnice Pizen Gynekologicko-pordnicka klinika

Plzen-Lochotin, , Czechia

Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum, Szuleszeti es Nogyogyaszati Klinika

Debrecen, Hajdú-Bihar, Hungary

Fovarosi Onkormanyzat Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet, Szuleszet - Nogyogyaszat

Budapest, , Hungary

Petz Aladar Megyei Oktato Korhaz, Szuleszet-Nogyogyaszat

Győr, , Hungary

Bacs-Kiskun Megyei Onkormanyzat Korhaza, Svegedi Tudmanyegyetem Altalanos Orvostudomanyi kar Oktato Korhaza

Kecskemét, , Hungary

Josa Andras Oktato Korhaz Egeszsegugyi Szolgaltato Nonprofit Kft.

Nyíregyháza, , Hungary

Szegedi Tudomanyegyetem, Szuleszeti es Nogyogyaszati Klinika

Szeged, , Hungary

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

Bologna, , Italy

Azienda Ospedaliera di Bolzano Ospedale Generale Regionale di Bolzano

Bolzano, , Italy

Azienda Ospedaliera di Perugia - Ospedale Santa Maria dell a Misericordia

Perugia, , Italy

Northern State Medical University

Arkhangelsk, , Russia

Northern State Medical University

Arkhangelsk, , Russia

Belgorod Regional Clinical Hospital of St.Ioasaf

Belgorod, , Russia

State Educational Institution of Higher Professional Education "Kazan State Medical University of RosZdrav"

Kazan', , Russia

Kemerovo State Medical Academy

Kemerovo, , Russia

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, , Russia

State Educational Institution of Higher Professional Education "People's Friendship University of Russia" Department of Obstetrics and Gynecology with Course Perinatology

Moscow, , Russia

Russian National Research Medical University named after N.I. Pirogov

Moscow, , Russia

Municipal Healthcare Institution "Novosibirsk Municipal Perinatal Centre"

Novosibirsk, , Russia

Rostov Medical State University

Rostov-on-Don, , Russia

State Educational Institution of Higher Professional Education "St. Petersburg l.l Mechnikov State Medical Academy of RosZdrav" Department of Obstetrics, Gynecology and Perinatology

Saint Petersburg, , Russia

State Institution "D.O. Otto Scientific Institute for Obstetrics and Gynecology"

Saint Petersburg, , Russia

Almazov Federal Heart, Blood and Endocrinology Centre

Saint Petersburg, , Russia

Regional Perinatal Center

Tomsk, , Russia

State Healthcare Institution "Regional Maternity Hospital"

Yaroslavl, , Russia

Federal State Institution "Ural Research Institute of Maternity and Infancy Care of Rosmedtechnologies"

Yekaterinburg, , Russia

Hospital Universitari Vall D'Hebron

Barcelona, , Spain

Hospital Universitario Puerta del Mar

Cadiz, , Spain

Hospital Universitario Materno Infantil de Canarias

Las Palmas de Gran Canaria, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital 12 de Octubre

Madrid, , Spain

Hospital Virgen Del Rocio

Seville, , Spain

Hospital Universitario La Fe

Valencia, , Spain

"Hospital Universitario Miguel Servet

Zaragoza, , Spain

City Clinical Maternity Hospital #1

Chernivtsi, , Ukraine

Donets'k Regional Centre of Mother and Child Care

Donets'k, , Ukraine

Ivano-Frankivs'k Regional Prenatal Center, department of pregnant pathology

Ivano-Frankivsk, , Ukraine

<<Institute of Pediatrics, Obstetrics and Gynecology of AMS Ukraine>> Department of Rehabilitation and Reproduktive function of Women

Kyiv, , Ukraine

Polyclinic #1, Obolon district of Kyiv, maternity welfare department

Kyiv, , Ukraine

Kyiv City Centre of Reproduction and perinatal medicine, obstetric department

Kyiv, , Ukraine

SI "Institute of pediatrics, obstetrics and gynecology of AMS of Ukraine". Department of extragenital pathology and postnatal rehabilitation

Kyiv, , Ukraine

Municipal Institution "Maternity Hospital #1"

Odesa, , Ukraine

Ternopil' Municipal Hospital # 2

Ternopil, , Ukraine

Uzhgorod Municipal prenatal Centre, maternity welfare department #2

Uzhhorod, , Ukraine

Clinical Maternity Hospital No 4

Zaporizhzhya, , 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

Countries

United States; Bulgaria; Canada; Czechia; Hungary; Italy; Russia; Spain; Ukraine

References

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.

Reference Type: DERIVED

PMID: 31652479 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

17P-ES-003

Identifier Type: -

Identifier Source: org_study_id