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Preterm BirthPhase 3NCT00099164

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

A Phase 3 study testing 17 alpha-hydroxyprogesterone caproate (17P) in people with Preterm Birth and Pregnancy, run by The George Washington University Biostatistics Center at 14 sites in United States.

Completed

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

Official record
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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… Read more about this study

Who is it for?
Any age, women onlyHealthy volunteers can take part
Conditions the study is for
Preterm Birth, Pregnancy, Multifetal
What is being tested?
17 alpha-hydroxyprogesterone caproate (17P)
Type of treatment
Injection or infusion
How many people
795 participants
Where
14 sitesUnited States
Study dates
Apr 2004to Sep 2007
Phase
Phase 3
Are there results?
None posted in the registry

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 Any age
  • Women only
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 17Show fewer
  • 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.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites
  • University of Alabama - Birmingham

    Birmingham, Alabama, 35233

  • University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Northwestern University

    Chicago, Illinois, 60611

  • Case Western University

    Cleveland, Ohio, 44109

  • Ohio State University

    Columbus, Ohio, 43210

  • University of Texas - Southwest

    Dallas, Texas, 75235

  • Wayne State University

    Detroit, Michigan, 48201

  • University of Texas - Houston

    Houston, Texas, 77030

  • Columbia University

    New York, New York, 10032

  • Dexel University

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburgh Magee Womens Hospital

    Pittsburgh, Pennsylvania, 15213

  • Brown University

    Providence, Rhode Island, 02905

  • University of Utah Medical Center

    Salt Lake City, Utah, 84132

  • Wake Forest University School of Medicine

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
17 alpha-hydroxyprogesterone caproate (17P)
Keywords
preterm birth, pregnancy, multifetal, Progesterone
Medical subject headings
Premature Birth

What participants receive

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

  • 17 alpha-hydroxyprogesterone caproate (17P)Drug

    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.

What is being measured

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

  1. Delivery prior to 35 weeks 0 days gestation

    Measured: Delivery Date

Secondary outcomes (27)
  1. Maternal randomization to delivery interval of first fetus

    Measured: Delivery

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

    Measured: Duration of pregnancy

  3. Indicated preterm delivery

    Measured: Delivery

  4. Spontaneous preterm delivery

    Measured: Delivery

  5. Cesarean delivery

    Measured: Delivery

  6. Gestational age at delivery

    Measured: Length of pregnancy

  7. Placement of cervical cerclage

    Measured: During pregnancy

  8. Maternal hospital days

    Measured: Delivery

  9. Maternal complications such as preeclampsia, gestational diabetes, placental abruption, chorioamnionitis.

    Measured: Duration of pregnancy, delivery

  10. 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

    Measured: Early life

  11. Fetal and neonatal death

    Measured: Delivery, Early life

  12. Stillbirth

    Measured: Delivery

  13. Twin-twin transfusion syndrome

    Measured: During pregnancy

  14. Birth weight and degree of birth weight discordance

    Measured: Birth

  15. Infant days in hospital, *Respiratory distress syndrome (RDS)

    Measured: Early life

  16. Transient tachypnea of the newborn (TTN)

    Measured: Early life

  17. Bronchopulmonary dysplasia (BPD)/chronic lung disease

    Measured: Early life

  18. Persistent pulmonary hypertension of the newborn (PPHN)

    Measured: Early life

  19. Duration of ventilator support

    Measured: Early life

  20. Duration of supplemental oxygen

    Measured: Early life

  21. Periventricular leukomalacia (PVL)

    Measured: Early life

  22. Intraventricular hemorrhage (IVH)

    Measured: Early life

  23. Necrotizing enterocolitis (NEC)

    Measured: Early life

  24. Neonatal sepsis/meningitis/urinary tract infection/ pneumonia

    Measured: Early life

  25. Seizures, as documented by the attending physician

    Measured: Early life

  26. Retinopathy of prematurity (ROP)

    Measured: Early life

  27. Small for gestational age (<10th percentile).

    Measured: Early life

Timeline

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

  1. First posted9 Dec 2004 (estimated)
  2. Study startApr 2004
  3. Primary completionAug 2006
  4. Study completionSep 2007

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
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
795 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00099164
Sponsor's protocol ID
HD36801-STTARS
Other IDs
HD21410, HD27869, HD27917, HD27860, HD27915, HD34116, HD34208, HD34136
Status last verified
Feb 2019
First submitted
8 Dec 2004
Last updated
21 Feb 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 12802023
  • 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.

    PubMed 11926251
  • 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.

    PubMed 7898832
  • 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.

    PubMed 10819867
  • 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.

    PubMed 12699803
  • 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.

    PubMed 8885774
  • 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.

    PubMed 19155896
  • 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.

    PubMed 17671253
  • 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.

    PubMed 19716543
  • 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.

    PubMed 25425377
  • 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.

    PubMed 21620357

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 17 alpha-hydroxyprogesterone caproate (17P) in people with Preterm Birth and Pregnancy, run by The George Washington University Biostatistics Center at 14 sites in United States.

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 3 inclusion and 17 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 21 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. 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. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Delivery prior to 35 weeks 0 days gestation (time frame: Delivery Date). 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 NCT00099164, which also lists 11 linked publications.

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 21 Feb 2019.

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