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Trial of Progesterone in Twins and Triplets to Prevent Preterm Birth (STTARS)

This study has been completed.
Sponsor:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00099164
First received: December 8, 2004
Last updated: December 16, 2009
Last verified: November 2009
  Purpose

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.


Condition Intervention Phase
Preterm Birth
Pregnancy
Multifetal
Drug: 17 alpha-hydroxyprogesterone caproate (17P)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized Trial of 17 Alpha-Hydroxyprogesterone Caproate for Prevention of Preterm Birth in Multifetal Gestation (STTARS)

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Delivery prior to 35 weeks 0 days gestation [ Time Frame: Delivery Date ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maternal randomization to delivery interval of first fetus [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • pPROM - spontaneous rupture of the membranes at least one hour prior to the start of labor, regular contractions accompanied by cervical change [ Time Frame: Duration of pregnancy ] [ Designated as safety issue: No ]
  • Indicated preterm delivery [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Spontaneous preterm delivery [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Cesarean delivery [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Gestational age at delivery [ Time Frame: Length of pregnancy ] [ Designated as safety issue: No ]
  • Placement of cervical cerclage [ Time Frame: During pregnancy ] [ Designated as safety issue: No ]
  • Maternal hospital days [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Maternal complications such as preeclampsia, gestational diabetes, placental abruption, chorioamnionitis. [ Time Frame: Duration of pregnancy, delivery ] [ Designated as safety issue: No ]
  • Composite neonatal outcome, comprised of fetal or infant death, RDS, IVH (grades 3 and 4), PVL, NEC (stage II and III), BPD/chronic lung disease, ROP (stage III or higher), early onset sepsis including meningitis [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Fetal and neonatal death [ Time Frame: Delivery, Early life ] [ Designated as safety issue: No ]
  • Stillbirth [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Twin-twin transfusion syndrome [ Time Frame: During pregnancy ] [ Designated as safety issue: No ]
  • Birth weight and degree of birth weight discordance [ Time Frame: Birth ] [ Designated as safety issue: No ]
  • Infant days in hospital, *Respiratory distress syndrome (RDS) [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Transient tachypnea of the newborn (TTN) [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Bronchopulmonary dysplasia (BPD)/chronic lung disease [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Persistent pulmonary hypertension of the newborn (PPHN) [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Duration of ventilator support [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Duration of supplemental oxygen [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Periventricular leukomalacia (PVL) [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Intraventricular hemorrhage (IVH) [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Necrotizing enterocolitis (NEC) [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Neonatal sepsis/meningitis/urinary tract infection/ pneumonia [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Seizures, as documented by the attending physician [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Retinopathy of prematurity (ROP) [ Time Frame: Early life ] [ Designated as safety issue: No ]
  • Small for gestational age (<10th percentile). [ Time Frame: Early life ] [ Designated as safety issue: No ]

Enrollment: 795
Study Start Date: April 2004
Study Completion Date: September 2007
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 17 alpha-hydroxyprogesterone caproate (17P)
    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.
Detailed Description:

Women with multifetal gestation face numerous risks in excess of those faced by women with singleton gestation. Preterm birth is by far the most common and the most significant of these problems, yet no intervention or approach has served to reduce this risk. The prevalence of preterm birth has risen dramatically in recent years, in large part due to Assisted Reproductive Technologies. Consequently, the problem of preterm birth has assumed an even greater role in contributing to perinatal morbidity and mortality. The recently completed trial by the NICHD sponsored Maternal Fetal Medicine Units (MFMU) Network has, for the first time, demonstrated a treatment (i.e. progesterone therapy) that substantially reduces the rate of preterm birth in women at high risk for preterm delivery because of a prior spontaneous preterm birth . Preterm birth was reduced by 35% among progesterone-treated women when compared with women receiving placebo. Given this dramatic benefit and the extremely high risk of preterm birth in women with multifetal gestation, a trial to evaluate the benefit of progesterone in women with multifetal pregnancy is appropriate and timely. This protocol outlines a randomized, double-masked clinical trial comparing weekly treatment by injection of 17 alpha-hydroxyprogesterone caproate (17P) with placebo in women with twin or triplet gestation. In an ancillary study, the pharmacokinetics and pharmacodynamics of 17P in multifetal gestation will be studied.

This trial aims to enroll six hundred women with twin gestation and one hundred twenty women with triplet gestation between 16 weeks 0 days to 20 weeks 6 days. At the initial screening evaluation, and after signing the informed consent form, the patient will receive an injection of the placebo (1 ml inert castor oil). She will be asked to return after three days for randomization. During this compliance test period, an ultrasound exam will be scheduled, if not previously done. When the patient returns and if she still meets the inclusion criteria, she will be randomized to one of two treatments:

  • 17 a-hydroxyprogesterone caproate: weekly 1 ml injections containing 250 mg of 17P
  • Placebo: weekly injections of 1 ml placebo inert castor oil

Treatment will be given through 34 weeks 6 days gestation or delivery. At the time of consent to the main study, the patient will also be asked to participate in an ancillary study. If she agrees, she will have 30 cc of blood drawn at 24-28 weeks and at 32-35 weeks gestation. A pelvic exam will be done at the same two times to collect vaginal specimens and to determine Bishop score.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • Prenatal follow-up or delivery planned elsewhere (unless the study visits can be made as scheduled and complete outcome information can be obtained)
  • Participation in this trial in a previous pregnancy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00099164

Locations
United States, Alabama
University of Alabama - Birmingham
Birmingham, Alabama, United States, 35233
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Wake Forest University School of Medicine
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Case Western University
Cleveland, Ohio, United States, 44109
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Dexel University
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh Magee Womens Hospital
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Brown University
Providence, Rhode Island, United States, 02905
United States, Texas
University of Texas - Southwest
Dallas, Texas, United States, 75235
University of Texas - Houston
Houston, Texas, United States, 77030
United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Investigators
Study Director: Catherine Spong, MD Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Elizabeth A Thom, Ph.D. George Washington University Biostatistics Center
Study Chair: Dwight Rouse, MD University of Alabama at Birmingham
Study Chair: Steve N Caritis, MD University of Pittsburgh - Magee Womens Hospital
  More Information

Additional Information:
Publications:
Caritis SN, Rouse DJ, Peaceman AM, Sciscione A, Momirova V, Spong CY, Iams JD, Wapner RJ, Varner MW, Carpenter M, Lo J, Thorp J, Mercer BM, Sorokin Y, Harper M, Ramin S, Anderson G, for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of preterm birth in triplets using 17 alpha hydroxyprogesterone caproate: a randomized controlled trial. Obstetrics and Gynecology, 113:285-292, 2009.
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 for the 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. New England Journal of Medicine, 357:454-61, 2007.
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; for the 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. American Journal of Obstetrics and Gynecology. 201:392.e1-392.e5, 2009.PMCID: 2759383.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Catherine Y Spong, MD, Chief, Pregnancy and Perinatology Branch, NICHD, NIH
ClinicalTrials.gov Identifier: NCT00099164     History of Changes
Other Study ID Numbers: HD36801-STTARS, HD21410, HD27869, HD27917, HD27860, HD27915, HD34116, HD34208, HD34136, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, HD36801
Study First Received: December 8, 2004
Last Updated: December 16, 2009
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
preterm birth
pregnancy
multifetal
Progesterone

Additional relevant MeSH terms:
Premature Birth
Obstetric Labor Complications
Obstetric Labor, Premature
Pregnancy Complications
11-hydroxyprogesterone
17-alpha-hydroxy-progesterone caproate
Progesterone
Estradiol Antagonists
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Progestins

ClinicalTrials.gov processed this record on November 24, 2014