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Preterm BirthPhase 3PROLONGNCT01004029

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

A Phase 3 study testing Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL in people with Preterm Birth, run by AMAG Pharmaceuticals, Inc. at 104 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Preterm Birth
What is being tested?
Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,740 participants
Where
104 sitesin 9 countries
Study dates
Oct 2009to Oct 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 16Show fewer
  • 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.
  • 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.
  • 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.

Trial locations and contacts

104 sites in 9 countries.

104 sites in 9 countries

United States41 sites
  • Steven Z. Lenowitz, MD, LLC

    Bel Air, Maryland, 21014

  • Mid Dakota clinicl, PC Center for Women

    Bismarck, North Dakota, 58501

  • The Women's Clinic

    Boise, Idaho, 83712

  • Visions Clinical Research

    Boynton Beach, Florida, 33472

  • Women's Associates, P.C.

    Colorado Springs, Colorado, 80903

  • SC Clinical Research Center, LLC

    Columbia, South Carolina, 29201

  • Practice Research Organization, Inc.

    Dallas, Texas, 75230

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • HWC Women's Research Center

    Englewood, Ohio, 45322

  • Womack Army Medical Center

    Fort Bragg, North Carolina, 28310

  • Carl R. Darnall Army Medical Center

    Fort Hood, Texas, 76544

  • San Antonio Military Medical Center

    Fort Sam Houston, Texas, 78236

  • Female Pelvic Medicine and Urogynecology Institute of Michigan

    Grand Rapids, Michigan, 49503

  • Greenville Hospital System University Medical Group

    Greenville, South Carolina, 29605

  • Tripler Army Medical Center

    Honolulu, Hawaii, 96859

  • Rosemark Women Care Specialists

    Idaho Falls, Idaho, 83404

  • Grossmont Center for Clinical Research

    La Mesa, California, 91942

  • Palm Beach Obstetrics & Gynecology, PA (Altus Research)

    Lake Worth, Florida, 33407

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

    Lakewood, Colorado, 80228

  • Tanner Clinic

    Layton, Utah, 84041

  • University of Louisville

    Louisville, Kentucky, 40202

  • Women's Care Physicians/Obstetrical Specialists, PLLC

    Louisville, Kentucky, 40207

  • Research Associates Rio Grande Valley

    McAllen, Texas, 78503

  • Women's Physician's Group, MPLLC

    Memphis, Tennessee, 38104

  • Wheaton Franciscan Healthcare - St. Joseph Campus

    Milwaukee, Wisconsin, 53210

  • Drug Research & Analysis Corporation

    Montgomery, Alabama, 36106

  • Global OB/GYN Centers

    Pembroke Pines, Florida, 33024

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Temple University School of Medicine

    Philadelphia, Pennsylvania, 19140

  • Mt. Timpanogos Women's Health Care

    Pleasant Grove, Utah, 84062

  • Naval Medical Center - Portsmouth

    Portsmouth, Virginia, 23708

  • New Millennium Obstetrics & Gynecology, LLc

    Riverdale, Georgia, 30274

  • Saginaw Valley Medical Research Group, LLC

    Saginaw, Michigan, 48604

  • Naval Medical Center San Diego - Department of Obstetrics and Gynecology

    San Diego, California, 92134-5000

  • Salt Lake Women's Center, P.C.

    Sandy City, Utah, 84070

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Madigan Army Medical Center

    Tacoma, Washington, 98431

  • Tucson Medical Center (Watching Over Mothers and Babies Foundation)

    Tucson, Arizona, 85712

  • Womens Health Specialists

    West Hills, California, 91307

  • Lyndhurst Clinical Research

    Winston-Salem, North Carolina, 27103

  • Triad Research Partners, LLC

    Winston-Salem, North Carolina, 27103

Other trials in United States

Russia16 sites
  • Northern State Medical University

    Arkhangelsk, 163000

  • Northern State Medical University

    Arkhangelsk

  • Belgorod Regional Clinical Hospital of St.Ioasaf

    Belgorod

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

    Kazan', 420012

  • Kemerovo State Medical Academy

    Kemerovo

  • 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, 660100

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

    Moscow, 117333

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

    Moscow

  • Municipal Healthcare Institution "Novosibirsk Municipal Perinatal Centre"

    Novosibirsk, 630089

  • Rostov Medical State University

    Rostov-on-Don, 344029

  • 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, 195257

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

    Saint Petersburg, 199034

  • Almazov Federal Heart, Blood and Endocrinology Centre

    Saint Petersburg

  • Regional Perinatal Center

    Tomsk

  • State Healthcare Institution "Regional Maternity Hospital"

    Yaroslavl, 150003

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

    Yekaterinburg, 620028

Other trials in Russia

Ukraine12 sites
  • City Clinical Maternity Hospital #1

    Chernivtsi

  • Donets'k Regional Centre of Mother and Child Care

    Donets'k, 83114

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

    Ivano-Frankivsk

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

    Kyiv, 04050

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

    Kyiv, 04220

  • Kyiv City Centre of Reproduction and perinatal medicine, obstetric department

    Kyiv

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

    Kyiv

  • Municipal Institution "Maternity Hospital #1"

    Odesa, 65039

  • Ternopil' Municipal Hospital # 2

    Ternopil, 46001

  • Uzhgorod Municipal prenatal Centre, maternity welfare department #2

    Uzhhorod, 88017

  • Clinical Maternity Hospital No 4

    Zaporizhzhya, 69065

  • Department of Obstetrics and Gynecology of Zhaporizhzhya Medical Academy of Postgraduate Education on the Base of Healthcare Institution Maternity Hospital No 3

    Zhaporizhzhya, 69071

Other trials in Ukraine

Spain8 sites
  • Hospital Universitari Vall D'Hebron

    Barcelona, 08035

  • Hospital Universitario Puerta del Mar

    Cadiz, 11009

  • Hospital Universitario Materno Infantil de Canarias

    Las Palmas de Gran Canaria, 35016

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital 12 de Octubre

    Madrid

  • Hospital Virgen Del Rocio

    Seville

  • Hospital Universitario La Fe

    Valencia, 46009

  • "Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

Bulgaria6 sites
  • MHAT "Blagoevgrad", Department of obstetrics and Gynecology

    Blagoevgrad

  • Medical center "Teodora", LTD

    Rousse

  • MHAT "Silistra", Obstetrics and Gynecology Department

    Silistra

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

    Sofia

  • Medical Centre "Avicena" Ltd

    Sofia

  • SHAT " Sheinovo ",PLS, Maternity Clinic

    Sofia

Other trials in Bulgaria

Canada6 sites
  • University of Calgary - Foothills Hospital

    Calgary, Alberta, AB T2N 2T9

  • Lion's Gate Hospital (University of BC)

    North Vancouver, British Columbia, V7M 2H5

  • Glazier Medical Centre

    Oshawa, Ontario, L1H2J9

  • The Ottawa Hospital, General Campus

    Ottawa, Ontario, K1H 8L6

  • Victory Reproductive Care

    Windsor, Ontario, N8W 5R7

  • J. Leung Obstetrics and Gynaecology

    Windsor, Ontario, N8X 3V6

Other trials in Canada

Czechia6 sites
  • Fakultni nemocnice Brno

    Brno, South Moravian, 62500

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

    České Budějovice, 37001

  • Fakultni nemocnice Hradec Kralove Porodnicka a gynekologicka klinika

    Hradec Králové, 500 05

  • Fakultni nemocnice Olomouc

    Olomouc, Olomouc Region, 77900

  • Fakultni nemocnice Ostrava Porodnicko-gynekologicka klinika

    Ostrava-Poruba, 70852

  • Fakultni nemocnice Pizen Gynekologicko-pordnicka klinika

    Plzen-Lochotin, 304 60

Other trials in Czechia

Hungary6 sites
  • Fovarosi Onkormanyzat Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet, Szuleszet - Nogyogyaszat

    Budapest, 1097

  • Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum, Szuleszeti es Nogyogyaszati Klinika

    Debrecen, Hajdú-Bihar, 4032

  • Petz Aladar Megyei Oktato Korhaz, Szuleszet-Nogyogyaszat

    Győr, 9024

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

    Kecskemét, 6000

  • Josa Andras Oktato Korhaz Egeszsegugyi Szolgaltato Nonprofit Kft.

    Nyíregyháza, 4400

  • Szegedi Tudomanyegyetem, Szuleszeti es Nogyogyaszati Klinika

    Szeged, 6725

Other trials in Hungary

Italy3 sites
  • Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

    Bologna, 40100

  • Azienda Ospedaliera di Bolzano Ospedale Generale Regionale di Bolzano

    Bolzano, 39100

  • Azienda Ospedaliera di Perugia - Ospedale Santa Maria dell a Misericordia

    Perugia, 06132

Other trials in Italy

About this study

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

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.

Read the 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
Being tested
Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL, Vehicle
Keywords
17P, 17-HPC, 17-OHPC, 17-hydroxyprogesterone caproate, progestogens, preterm birth, recurrent preterm birth, spontaneous preterm birth
Medical subject headings
Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hydroxyprogesterone Caproate Injection (HPC), 250mg/mLDrug

    Also called Makena, 17P

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

  • VehicleDrug

    Also called Placebo

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

Study groups in NCT01004029
Study groupRoleWhat they receive
VehiclePlacebo comparatorCastor Oil
Receives: Drug: Vehicle
Hydroxyprogesterone Caproate Injection (HPC), 250 mg/mLActive comparatorHPC 250 mg/mL in oil
Receives: Drug: Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 35 weeks

  2. 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.

    Measured: Until 28 days of life or discharge from the neonatal intensive care unit (NICU), whichever occurred later.

Secondary outcomes (5)
  1. 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

    Measured: 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).

  2. Preterm Birth Prior to 32 Weeks Gestation

    Measured: Up to 32 weeks

  3. Preterm Birth Prior to 37 Weeks Gestation

    Measured: Up to 37 weeks

  4. Stillbirths

    Defined as all stillbirths/fetal deaths/in utero fetal losses occurring from 20 weeks gestation until term.

    Measured: 20 weeks gestation until term

  5. 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

    Measured: Until 28 days of life or discharge from the NICU whichever occurred later.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2009 (estimated)
  2. Study startOct 2009
  3. Primary completionOct 2018
  4. Study completionOct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,740 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01004029
Sponsor's protocol ID
17P-ES-003
Acronym
PROLONG
Status last verified
May 2022
First submitted
27 Oct 2009
Last updated
1 Jun 2022
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 31652479

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL in people with Preterm Birth, run by AMAG Pharmaceuticals, Inc. at 104 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 104 sites in United States, Russia, Ukraine, Spain, Bulgaria and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Preterm Birth <35 Weeks Gestation (time frame: Up to 35 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01004029, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2022.

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