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

Preterm Birth Clinical Trial

— PROLONG  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01004029
• Other study ID #: 17P-ES-003
• Status: Completed
• Phase: Phase 3
• Start date: October 2009
• Est. completion date: October 2018

Study information

• Verified date: May 2022
• Source: AMAG Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1740
• Est. completion date: October 2018
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Premature Birth
• Preterm Birth

Intervention

Drug:
• Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL
1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
• Vehicle
Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.

Locations

Country	Name	City	State
Bulgaria	MHAT "Blagoevgrad", Department of obstetrics and Gynecology	Blagoevgrad
Bulgaria	Medical center "Teodora", LTD	Russe
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
Canada	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	J. Leung Obstetrics and Gynaecology	Windsor	Ontario
Canada	Victory Reproductive Care	Windsor	Ontario
Czechia	Fakultni nemocnice Brno	Brno	Jihomoravsky KRAJ
Czechia	Nemocnice Ceske Budejovice, a.s. Gynekologicko-pordnicka klinika	Ceske Budejovice 7
Czechia	Fakultni nemocnice Hradec Kralove Porodnicka a gynekologicka klinika	Hradec Kralove
Czechia	Fakultni nemocnice Olomouc	Olomouc	Olomoucky KRAJ
Czechia	Fakultni nemocnice Ostrava Porodnicko-gynekologicka klinika	Ostrava-Poruba
Czechia	Fakultni nemocnice Pizen Gynekologicko-pordnicka klinika	Plzen-Lochotin
Hungary	Fovarosi Onkormanyzat Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet, Szuleszet - Nogyogyaszat	Budapest
Hungary	Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum, Szuleszeti es Nogyogyaszati Klinika	Debrecen	Hajdu-bihar
Hungary	Petz Aladar Megyei Oktato Korhaz, Szuleszet-Nogyogyaszat	Gyor
Hungary	Bacs-Kiskun Megyei Onkormanyzat Korhaza, Svegedi Tudmanyegyetem Altalanos Orvostudomanyi kar Oktato Korhaza	Kecskemet
Hungary	Josa Andras Oktato Korhaz Egeszsegugyi Szolgaltato Nonprofit Kft.	Nyiregyhaza
Hungary	Szegedi Tudomanyegyetem, Szuleszeti es Nogyogyaszati Klinika	Szeged
Italy	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
Russian Federation	Northern State Medical University	Arkhangelsk
Russian Federation	Northern State Medical University	Arkhangelsk
Russian Federation	Belgorod Regional Clinical Hospital of St.Ioasaf	Belgorod
Russian Federation	State Educational Institution of Higher Professional Education "Kazan State Medical University of RosZdrav"	Kazan
Russian Federation	Kemerovo State Medical Academy	Kemerovo
Russian Federation	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	Russian National Research Medical University named after N.I. Pirogov	Moscow
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	Municipal Healthcare Institution "Novosibirsk Municipal Perinatal Centre"	Novosibirsk
Russian Federation	Rostov Medical State University	Rostov-on-Don
Russian Federation	Almazov Federal Heart, Blood and Endocrinology Centre	Saint 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	State Institution "D.O. Otto Scientific Institute for Obstetrics and Gynecology"	St. Petersburg
Russian Federation	Regional Perinatal Center	Tomsk
Russian Federation	State Healthcare Institution "Regional Maternity Hospital"	Yaroslavl
Russian Federation	Federal State Institution "Ural Research Institute of Maternity and Infancy Care of Rosmedtechnologies"	Yekaterinburg
Spain	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 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Virgen Del Rocio	Sevilla
Spain	Hospital Universitario La Fe	Valencia
Spain	"Hospital Universitario Miguel Servet	Zaragoza
Ukraine	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-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	Polyclinic #1, Obolon district of Kyiv, maternity welfare 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"	Odessa
Ukraine	Ternopil' Municipal Hospital # 2	Ternopil
Ukraine	Uzhgorod Municipal prenatal Centre, maternity welfare department #2	Uzhgorod
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
United States	Steven Z. Lenowitz, MD, LLC	Bel Air	Maryland
United States	Mid Dakota clinicl, PC Center for Women	Bismarck	North Dakota
United States	The Women's Clinic	Boise	Idaho
United States	Visions Clinical Research	Boynton Beach	Florida
United States	Women's Associates, P.C.	Colorado Springs	Colorado
United States	SC Clinical Research Center, LLC	Columbia	South Carolina
United States	Practice Research Organization, Inc.	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	HWC Women's Research Center	Englewood	Ohio
United States	Womack Army Medical Center	Fort Bragg	North Carolina
United States	Carl R. Darnall Army Medical Center	Fort Hood	Texas
United States	San Antonio Military Medical Center	Fort Sam Houston	Texas
United States	Female Pelvic Medicine and Urogynecology Institute of Michigan	Grand Rapids	Michigan
United States	Greenville Hospital System University Medical Group	Greenville	South Carolina
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Rosemark Women Care Specialists	Idaho Falls	Idaho
United States	Grossmont Center for Clinical Research	La Mesa	California
United States	Palm Beach Obstetrics & Gynecology, PA (Altus Research)	Lake Worth	Florida
United States	Red Rocks OB/GYN - Physician's Research Options, LLC	Lakewood	Colorado
United States	Tanner Clinic	Layton	Utah
United States	University of Louisville	Louisville	Kentucky
United States	Women's Care Physicians/Obstetrical Specialists, PLLC	Louisville	Kentucky
United States	Research Associates Rio Grande Valley	McAllen	Texas
United States	Women's Physician's Group, MPLLC	Memphis	Tennessee
United States	Wheaton Franciscan Healthcare - St. Joseph Campus	Milwaukee	Wisconsin
United States	Drug Research & Analysis Corporation	Montgomery	Alabama
United States	Global OB/GYN Centers	Pembroke Pines	Florida
United States	Temple University School of Medicine	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Mt. Timpanogos Women's Health Care	Pleasant Grove	Utah
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	New Millennium Obstetrics & Gynecology, LLc	Riverdale	Georgia
United States	Saginaw Valley Medical Research Group, LLC	Saginaw	Michigan
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Naval Medical Center San Diego - Department of Obstetrics and Gynecology	San Diego	California
United States	Salt Lake Women's Center, P.C.	Sandy	Utah
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Tucson Medical Center (Watching Over Mothers and Babies Foundation)	Tucson	Arizona
United States	Womens Health Specialists	West Hills	California
United States	Lyndhurst Clinical Research	Winston-Salem	North Carolina
United States	Triad Research Partners, LLC	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AMAG Pharmaceuticals, Inc.	ResearchPoint Global

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czechia,  Hungary,  Italy,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Preterm Birth <35 Weeks Gestation	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.	Up to 35 weeks
Primary	Neonatal Composite Index (NCI)	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.	Until 28 days of life or discharge from the neonatal intensive care unit (NICU), whichever occurred later.
Secondary	Fetal/Early Infant Death	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	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).
Secondary	Preterm Birth Prior to 32 Weeks Gestation		Up to 32 weeks
Secondary	Preterm Birth Prior to 37 Weeks Gestation		Up to 37 weeks
Secondary	Stillbirths	Defined as all stillbirths/fetal deaths/in utero fetal losses occurring from 20 weeks gestation until term.	20 weeks gestation until term
Secondary	Neonatal Deaths With =24 Weeks Gestational Age	Neonatal death (from minutes after birth until 28 days of life) occurring in liveborns born at 24 weeks gestation or greater	Until 28 days of life or discharge from the NICU whichever occurred later.