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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

December 8, 2004
December 16, 2009
April 2004
August 2006   (final data collection date for primary outcome measure)
Delivery prior to 35 weeks 0 days gestation [ Time Frame: Delivery Date ] [ Designated as safety issue: No ]
Delivery prior to 35 weeks 0 days gestation
Complete list of historical versions of study NCT00099164 on ClinicalTrials.gov Archive Site
  • 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 ]
  • MATERNAL OUTCOMES:
  • *Randomization to delivery interval of first fetus
  • *pPROM – spontaneous rupture of the membranes at least one hour prior to the start of labor, regular contractions accompanied by cervical change
  • *Indicated preterm delivery
  • *Spontaneous preterm delivery
  • *Cesarean delivery
  • *Gestational age at delivery
  • *Placement of cervical cerclage
  • *Maternal hospital days
  • *Maternal complications such as preeclampsia, gestational diabetes, placental abruption, chorioamnionitis.
  • NEONATAL OUTCOMES:
  • *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
  • *Fetal and neonatal death
  • *Stillbirth
  • *Twin-twin transfusion syndrome
  • *Birth weight and degree of birth weight discordance
  • *Infant days in hospital, *Respiratory distress syndrome (RDS)
  • *Transient tachypnea of the newborn (TTN)
  • *Bronchopulmonary dysplasia (BPD)/chronic lung disease
  • *Persistent pulmonary hypertension of the newborn (PPHN
  • *Duration of ventilator support
  • *Duration of supplemental oxygen
  • *Periventricular leukomalacia (PVL)
  • *Intraventricular hemorrhage (IVH)
  • *Necrotizing enterocolitis (NEC)
  • *Neonatal sepsis/meningitis/urinary tract infection/ pneumonia
  • *Seizures, as documented by the attending physician
  • *Retinopathy of prematurity (ROP)
  • *Small for gestational age (<10th percentile).
Not Provided
Not Provided
 
Trial of Progesterone in Twins and Triplets to Prevent Preterm Birth (STTARS)
A Randomized Trial of 17 Alpha-Hydroxyprogesterone Caproate for Prevention of Preterm Birth in Multifetal Gestation (STTARS)

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
  • Preterm Birth
  • Pregnancy
  • Multifetal
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.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
795
September 2007
August 2006   (final data collection date for primary outcome measure)

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.
Female
Not Provided
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00099164
HD36801-STTARS, HD21410, HD27869, HD27917, HD27860, HD27915, HD34116, HD34208, HD34136, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, HD36801
Yes
Catherine Y Spong, MD, Chief, Pregnancy and Perinatology Branch, NICHD, NIH
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not Provided
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
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
November 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP