NCT00099164

Brief Summary

Women pregnant with twins or triplets are at high risk of preterm birth, yet no intervention or approach has served to reduce this risk. A recently completed trial by the NICHD sponsored Maternal Fetal Medicine Units (MFMU) Network has, for the first time, demonstrated a treatment that substantially reduces the rate of preterm birth in women at high risk for preterm delivery (i.e. progesterone therapy). Preterm birth was reduced by 35% among progesterone-treated women with a singleton pregnancy when compared with women receiving placebo. The current trial compares weekly treatment by injection of progesterone with placebo in women pregnant with twins or triplets.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
795

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Apr 2004

Typical duration for phase_3

Geographic Reach
1 country

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2004

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

December 8, 2004

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 9, 2004

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2006

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2007

Completed
Last Updated

February 21, 2019

Status Verified

February 1, 2019

Enrollment Period

2.3 years

First QC Date

December 8, 2004

Last Update Submit

February 19, 2019

Conditions

Keywords

preterm birthpregnancymultifetalProgesterone

Outcome Measures

Primary Outcomes (1)

  • Delivery prior to 35 weeks 0 days gestation

    Delivery Date

Secondary Outcomes (27)

  • Maternal randomization to delivery interval of first fetus

    Delivery

  • pPROM - spontaneous rupture of the membranes at least one hour prior to the start of labor, regular contractions accompanied by cervical change

    Duration of pregnancy

  • Indicated preterm delivery

    Delivery

  • Spontaneous preterm delivery

    Delivery

  • Cesarean delivery

    Delivery

  • +22 more secondary outcomes

Interventions

Study coded medication is 250 mg of 17P as a 1 ml intramuscular injection (or 1 ml of placebo inert oil). Patients are seen weekly to administer the study drug through 34 weeks 6 days gestation or delivery, whichever occurs first.

Eligibility Criteria

Sexfemale
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Twin or triplet pregnancy. Quadruplets reduced to triplets may be included, but no other prior reductions.
  • Gestational age between 16 weeks 0 days to 20 weeks 6 days based on clinical information and evaluation of the first ultrasound.
  • Signed patient authorization and consent form.

You may not qualify if:

  • Prior elective fetal reduction in the current pregnancy, except in the case of a quadruplet gestation reduced to triplets.
  • Planned fetal reduction or planned termination
  • Monoamniotic gestation
  • Twin-twin transfusion syndrome
  • Fetal death or imminent fetal demise
  • Major fetal anomaly (e.g., gastroschisis, spina bifida, serious karyotypic abnormalities). An ultrasound examination from 12 weeks 0 days to 20 weeks 6 days by project estimated date of confinement (EDC) must be performed to rule out fetal anomalies
  • Discordance in fetal size, defined as a discrepancy of 3 or more weeks in gestational age by ultrasound between the largest and the smallest fetus. Diagnosis is based on measurements made at the ultrasound done between 12 weeks 0 days and 20 weeks 6 days gestation
  • Progesterone treatment used or planned after 14 weeks gestation
  • Heparin therapy at a dose ≥ 10,000 units per day of unfractionated heparin, or any low molecular weight heparin during the current pregnancy, or thromboembolic disease for which such heparin treatment is planned (because of contraindication to intra-muscular injections)
  • Current or planned cervical cerclage
  • Uterine anomaly (uterine didelphys, bicornate uterus)
  • Contraindication to intra-muscular injections
  • Maternal medical conditions, such as: known idiopathic thrombocytopenia purpura (ITP) or a known platelet count less than 100,000 per cubic millimeter (because of contraindication to intra-muscular injections), hypertension requiring medication, diabetes managed with insulin or oral hypoglycemic agents
  • Inability to arrange a pre-randomization ultrasound between 12 weeks 0 days and 20 weeks 6 days gestation
  • Participation in another interventional study that influences gestational age at delivery or neonatal morbidity or mortality
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

University of Alabama - Birmingham

Birmingham, Alabama, 35233, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Case Western University

Cleveland, Ohio, 44109, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Dexel University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Brown University

Providence, Rhode Island, 02905, United States

Location

University of Texas - Southwest

Dallas, Texas, 75235, United States

Location

University of Texas - Houston

Houston, Texas, 77030, United States

Location

University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

Location

Related Publications (11)

  • Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003 Jun 12;348(24):2379-85. doi: 10.1056/NEJMoa035140.

    PMID: 12802023BACKGROUND
  • Kogan MD, Alexander GR, Kotelchuck M, MacDorman MF, Buekens P, Papiernik E. A comparison of risk factors for twin preterm birth in the United States between 1981-82 and 1996-97. Matern Child Health J. 2002 Mar;6(1):29-35. doi: 10.1023/a:1014312132443.

    PMID: 11926251BACKGROUND
  • Gardner MO, Goldenberg RL, Cliver SP, Tucker JM, Nelson KG, Copper RL. The origin and outcome of preterm twin pregnancies. Obstet Gynecol. 1995 Apr;85(4):553-7. doi: 10.1016/0029-7844(94)00455-M.

    PMID: 7898832BACKGROUND
  • Min SJ, Luke B, Gillespie B, Min L, Newman RB, Mauldin JG, Witter FR, Salman FA, O'sullivan MJ. Birth weight references for twins. Am J Obstet Gynecol. 2000 May;182(5):1250-7. doi: 10.1067/mob.2000.104923.

    PMID: 10819867BACKGROUND
  • Lynch A, McDuffie R, Stephens J, Murphy J, Faber K, Orleans M. The contribution of assisted conception, chorionicity and other risk factors to very low birthweight in a twin cohort. BJOG. 2003 Apr;110(4):405-10.

    PMID: 12699803BACKGROUND
  • Goldenberg RL, Iams JD, Miodovnik M, Van Dorsten JP, Thurnau G, Bottoms S, Mercer BM, Meis PJ, Moawad AH, Das A, Caritis SN, McNellis D. The preterm prediction study: risk factors in twin gestations. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol. 1996 Oct;175(4 Pt 1):1047-53. doi: 10.1016/s0002-9378(96)80051-2.

    PMID: 8885774BACKGROUND
  • Caritis SN, Rouse DJ, Peaceman AM, Sciscione A, Momirova V, Spong CY, Iams JD, Wapner RJ, Varner M, Carpenter M, Lo J, Thorp J, Mercer BM, Sorokin Y, Harper M, Ramin S, Anderson G; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Maternal-Fetal Medicine Units Network (MFMU). Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial. Obstet Gynecol. 2009 Feb;113(2 Pt 1):285-92. doi: 10.1097/AOG.0b013e318193c677.

  • Rouse DJ, Caritis SN, Peaceman AM, Sciscione A, Thom EA, Spong CY, Varner M, Malone F, Iams JD, Mercer BM, Thorp J, Sorokin Y, Carpenter M, Lo J, Ramin S, Harper M, Anderson G; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl J Med. 2007 Aug 2;357(5):454-61. doi: 10.1056/NEJMoa070641.

  • Gyamfi C, Horton AL, Momirova V, Rouse DJ, Caritis SN, Peaceman AM, Sciscione A, Meis PJ, Spong CY, Dombrowski M, Sibai B, Varner MW, Iams JD, Mercer BM, Carpenter MW, Lo J, Ramin SM, O'Sullivan MJ, Miodovnik M, Conway D; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. The effect of 17-alpha hydroxyprogesterone caproate on the risk of gestational diabetes in singleton or twin pregnancies. Am J Obstet Gynecol. 2009 Oct;201(4):392.e1-5. doi: 10.1016/j.ajog.2009.06.036. Epub 2009 Aug 29.

  • Blumenfeld YJ, Momirova V, Rouse DJ, Caritis SN, Sciscione A, Peaceman AM, Reddy UM, Varner MW, Malone FD, Iams JD, Mercer BM, Thorp JM Jr, Sorokin Y, Carpenter MW, Lo J, Ramin SM, Harper M; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Accuracy of sonographic chorionicity classification in twin gestations. J Ultrasound Med. 2014 Dec;33(12):2187-92. doi: 10.7863/ultra.33.12.2187.

  • Caritis SN, Sharma S, Venkataramanan R, Rouse DJ, Peaceman AM, Sciscione A, Spong CY, Varner MW, Malone FD, Iams JD, Mercer BM, Thorp JM Jr, Sorokin Y, Carpenter M, Lo J, Ramin S, Harper M; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Pharmacokinetics of 17-hydroxyprogesterone caproate in multifetal gestation. Am J Obstet Gynecol. 2011 Jul;205(1):40.e1-8. doi: 10.1016/j.ajog.2011.03.028. Epub 2011 Mar 22.

Related Links

MeSH Terms

Conditions

Premature Birth

Interventions

17 alpha-Hydroxyprogesterone Caproate

Condition Hierarchy (Ancestors)

Obstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Intervention Hierarchy (Ancestors)

17-alpha-HydroxyprogesteroneHydroxyprogesteronesProgesteronePregnenedionesPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsProgesterone CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Menachem Miodovnik, M.D.

    NICHD Project Scientist

    STUDY DIRECTOR
  • Elizabeth A Thom, Ph.D.

    George Washington University Biostatistics Center

    PRINCIPAL INVESTIGATOR
  • Dwight Rouse, MD

    University of Alabama at Birmingham

    STUDY CHAIR
  • Steve N Caritis, MD

    University of Pittsburgh - Magee Womens Hospital

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 8, 2004

First Posted

December 9, 2004

Study Start

April 1, 2004

Primary Completion

August 1, 2006

Study Completion

September 1, 2007

Last Updated

February 21, 2019

Record last verified: 2019-02

Data Sharing

IPD Sharing
Will share

The data will be shared after completion and publication of the main analyses in accordance with NIH policy. The dataset can be obtained by emailing mfmudatasets@bsc.gwu.edu.

Locations