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

Pregnancy Clinical Trial

Official title:

A Randomized Trial of 17 Alpha-Hydroxyprogesterone Caproate for Prevention of Preterm Birth in Multifetal Gestation (STTARS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00099164
• Other study ID #: HD36801-STTARS
• Secondary ID: HD21410HD27869HD
• Status: Completed
• Phase: Phase 3
• Start date: April 2004
• Est. completion date: September 2007

Study information

• Verified date: February 2019
• Source: The George Washington University Biostatistics Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 795
• Est. completion date: September 2007
• Est. primary completion date: August 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Multifetal
• Pregnancy
• Premature Birth
• Preterm Birth

Intervention

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.

Locations

Country	Name	City	State
United States	University of Alabama - Birmingham	Birmingham	Alabama
United States	University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Case Western University	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	University of Texas - Southwest	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	University of Texas - Houston	Houston	Texas
United States	Columbia University	New York	New York
United States	Dexel University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	Brown University	Providence	Rhode Island
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
The George Washington University Biostatistics Center	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (9)

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 Develo — View Citation

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. — View Citation

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. — View Citation

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 I — View Citation

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. — View Citation

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. — View Citation

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. Erratum in: N Engl J Med. 2003 Sep 25;349(13):1299. — View Citation

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. — View Citation

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 Medici — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delivery prior to 35 weeks 0 days gestation		Delivery Date
Secondary	Maternal randomization to delivery interval of first fetus		Delivery
Secondary	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
Secondary	Indicated preterm delivery		Delivery
Secondary	Spontaneous preterm delivery		Delivery
Secondary	Cesarean delivery		Delivery
Secondary	Gestational age at delivery		Length of pregnancy
Secondary	Placement of cervical cerclage		During pregnancy
Secondary	Maternal hospital days		Delivery
Secondary	Maternal complications such as preeclampsia, gestational diabetes, placental abruption, chorioamnionitis.		Duration of pregnancy, delivery
Secondary	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		Early life
Secondary	Fetal and neonatal death		Delivery, Early life
Secondary	Stillbirth		Delivery
Secondary	Twin-twin transfusion syndrome		During pregnancy
Secondary	Birth weight and degree of birth weight discordance		Birth
Secondary	Infant days in hospital, *Respiratory distress syndrome (RDS)		Early life
Secondary	Transient tachypnea of the newborn (TTN)		Early life
Secondary	Bronchopulmonary dysplasia (BPD)/chronic lung disease		Early life
Secondary	Persistent pulmonary hypertension of the newborn (PPHN)		Early life
Secondary	Duration of ventilator support		Early life
Secondary	Duration of supplemental oxygen		Early life
Secondary	Periventricular leukomalacia (PVL)		Early life
Secondary	Intraventricular hemorrhage (IVH)		Early life
Secondary	Necrotizing enterocolitis (NEC)		Early life
Secondary	Neonatal sepsis/meningitis/urinary tract infection/ pneumonia		Early life
Secondary	Seizures, as documented by the attending physician		Early life
Secondary	Retinopathy of prematurity (ROP)		Early life
Secondary	Small for gestational age (<10th percentile).		Early life

External Links

•   The public website of the NICHD Maternal Fetal Medicine Units (MFMU) Network