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CompletedNCT00615550Updated Mar 13, 2012Results posted

PREGNANT Short Cervix Trial

A Phase 3 interventional study of progesterone and placebo in Preterm Delivery, Short Cervix and Short Uterine Cervical Length, sponsored by Juniper Pharmaceuticals, Inc.. Completed at 49 sites in 10 countries. Open to female participants aged 15 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2012-03-13.

Sponsored by Juniper Pharmaceuticals, Inc. · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
465
Allocation
Randomized
Ages
15 Years to 45 Years
Sex
Female
01

Study summary

The purpose of this research study is to evaluate the usefulness of progesterone vaginal gel in decreasing the preterm birth rate in a population of pregnant women with short cervical length and at high risk for preterm birth.

Read the detailed description

A Short uterine cervical length in the mid-trimester is the most powerful predictor of preterm birth.

02

Conditions studied

  • Preterm Delivery
  • Short Cervix
  • Short Uterine Cervical Length

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Keywords

  • Preterm
  • Cervix
03

In context

Premature Birth

2,554 studies on the registry are indexed under Premature Birth; 498 are open to participants now.

This study's enrollment of 465 is above the median of 84 across 1,689 interventional studies indexed under Premature Birth.

Browse Premature Birth studies →

Lead sponsor

Juniper Pharmaceuticals, Inc. is the lead sponsor of 4 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
15 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  1. The subject has a short cervical length by transvaginal ultrasound (TVU) defined as 10-20mm. In cases of "dynamic cervix", the shortest observed/documented cervical length by TVU is to be used as the cervical length for inclusion purposes.
  2. Singleton gestation.
  3. The pregnancy has an estimated gestational age between 19 0/7 weeks and 23 6/7 weeks.
  4. Maternal age between 15 (or local age of majority/emancipation) and 45 years of age at the time of screening. An alternative age range can be accepted according to the standards and applicable regulations of the study centers.
  5. The subject speaks either English or a common local language.
  6. The subject has voluntarily signed the Informed Consent Form and associated forms after having the contents explained, and all her questions are answered to her satisfaction and understanding.
  7. In the opinion of the investigator, the subject is able to understand the study and is able to give informed consent, as well as participate in it and adhere to study procedures.

Exclusion criteria

Exclusion Criteria:

  1. The subject has a cervical length \<10 or >20mm.
  2. The subject has a multifetal gestation.
  3. The subject has or is scheduled to have a cervical cerclage prior to randomization. According to ACOG Practice Bulletin Number 48 (November 2003), cerclage can be considered in a subject with a history of 3 or more unexplained midtrimester pregnancy losses or preterm deliveries.228,229
  4. Subjects diagnosed to have acute cervical insufficiency with bulging membranes passing the external os.
  5. The subject has a previous history of an adverse reaction to progesterone or any component present in Prochieve® 8% vaginal gel.
  6. The subject has been treated with a progestogen within the previous 4 weeks.
  7. The subject is currently being treated for a seizure disorder, has an unstable psychiatric disorder, is taking antihypertensive therapy for chronic hypertension at the time of enrollment, has a history of congestive heart failure or chronic renal failure, or has uncontrolled diabetes mellitus (known end-organ dysfunction secondary to vascular disease).
  8. The subject has active thrombophlebitis or a thromboembolic disorder, or a history of hormone-associated thrombophlebitis or thromboembolic disorders.
  9. The subject has active liver dysfunction or disease.
  10. The subject has known or suspected malignancy of the breast or genital organs.
  11. The subject is currently participating in another interventional study or has participated in an interventional drug study within one month prior to screening for this study.
  12. The subject's current pregnancy is complicated by a major fetal anomaly or known chromosomal abnormality.
  13. The subject has a uterine anatomic malformation (bicornuate uterus, septate uterus)
  14. The subject, in the judgment of the investigator, will be unable or unwilling to comply with study-related assessments and procedures.
  15. The subject currently has preterm rupture of membranes, vaginal bleeding, known or suspected amnionitis, or signs or symptoms of preterm labor at the time of enrollment.
  16. The subject is HIV positive with a CD4 count of \<350 cells/mm3 and is receiving more than one (1) medication to prevent the transfer of AIDS to the fetus.
  17. Complete placenta previa.
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
465 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    placebo vaginal gel

    Drug: placebo

  • Active comparator
    Prochieve

    Progesterone 8% Vaginal Gel

    Drug: progesterone

Interventions

  • Drugprogesterone

    8% vaginal gel, 1.125 Grams once daily, beginning at 19 0/7 to 23 6/7 weeks gestation through 36 6/7 weeks gestation

    Also known as: Prochieve 8%

  • Drugplacebo

    vaginal gel, 1.125 Grams once daily, beginning at 19 0/7 to 23 6/7 weeks gestation through 36 6/7 weeks gestation

06

What researchers measure

Primary outcomes

  1. Number of Participants With Birth <=32 6/7 Weeks Gestation.

    Time frame: 9 to 13 weeks

Secondary outcomes

  1. Number of Infants With Neonatal Morbidities Such as Respiratory Distress Syndrome (RDS), Bronchopulmonary Dysplasia (BPD), Intraventricular Hemorrhage (IVH), Proven Sepsis, and Necrotizing Enterocolitis (NEC)

    Each infant is scored based on the 7 morbidity and mortality events above: 0= no morbidity event 1. 1 morbidity event 2. 2 morbidity events 3. 3 or more morbidity events 4. mortality

    Time frame: Delivery Hospitalization (1-212 days)

  2. Number of Subjects With Preterm Birth at ≤27 6/7, ≤34 6/7, and <36 6/7 Weeks Gestation.

    Number of participants at \<=27 6/7 , \<=34 6/7, and \<36 6/7.

    Time frame: Gestational Age at Delivery

  3. Number of Neonates Who Died.

    Time frame: Delivery to 28 days

  4. Number of Infants With a Birth Weight < 1500 Grams or < 2500 Grams

    Assessment of birth weight \< 1500 grams or \< 2500 grams

    Time frame: date of delivery

07

Results

Posted Mar 13, 2012
Limitations and caveats
Trial not powered for subgroup analysis.

Participant flow

March 2008 to June 2010

Participant flow — Overall Study
MilestonePlaceboProchieve
Started229236
Completed223235
Not completed61
Withdrew: Lost to follow-up61

Outcome measures

PrimaryNumber of Participants With Birth <=32 6/7 Weeks Gestation.
Time frame:
9 to 13 weeks
Reported as:
Number · participants
Number of Participants With Birth <=32 6/7 Weeks Gestation.
participantsPlaceboProchieve
Number of Participants With Birth <=32 6/7 Weeks Gestation.3621
Statistical analysis
  • Placebo vs Prochieve · Cochran-Mantel-Haenszel · p = 0.020 · Risk ratio (rr): 0.55 · 95% CI 0.33 to 0.92
SecondaryNumber of Infants With Neonatal Morbidities Such as Respiratory Distress Syndrome (RDS), Bronchopulmonary Dysplasia (BPD), Intraventricular Hemorrhage (IVH), Proven Sepsis, and Necrotizing Enterocolitis (NEC)

Each infant is scored based on the 7 morbidity and mortality events above: 0= no morbidity event 1. 1 morbidity event 2. 2 morbidity events 3. 3 or more morbidity events 4. mortality

Time frame:
Delivery Hospitalization (1-212 days)
Reported as:
Number · participants
Number of Infants With Neonatal Morbidities Such as Respiratory Distress Syndrome (RDS), Bronchopulmonary Dysplasia (BPD), Intraventricular Hemorrhage (IVH), Proven Sepsis, and Necrotizing Enterocolitis (NEC)
participantsPlaceboProchieve
Composite score 0192217
Composite score 1115
Composite score 282
Composite score 303
Composite score 4118
Infants with RDS177
Statistical analysis
  • Placebo vs Prochieve · Cochran-Mantel-Haenszel · p = 0.048
  • Placebo vs Prochieve · Cochran-Mantel-Haenszel · p = 0.026 · Risk ratio (rr): 0.39 · 95% CI 0.17 to 0.92
SecondaryNumber of Subjects With Preterm Birth at ≤27 6/7, ≤34 6/7, and <36 6/7 Weeks Gestation.

Number of participants at \<=27 6/7 , \<=34 6/7, and \<36 6/7.

Time frame:
Gestational Age at Delivery
Reported as:
Number · participants
Number of Subjects With Preterm Birth at ≤27 6/7, ≤34 6/7, and <36 6/7 Weeks Gestation.
participantsPlaceboProchieve
Number of deliveries <= 27 6/7 weeks2312
Number of deliveries <= 34 6/7 weeks5234
Number of deliveries <= 36 weeks7671
Statistical analysis
  • Placebo vs Prochieve · Cochran-Mantel-Haenszel · p = 0.036 · Risk ratio (rr): 0.5 · 95% CI 0.25 to 0.97
  • Placebo vs Prochieve · Cochran-Mantel-Haenszel · p = 0.016 · Risk ratio (rr): 0.62 · 95% CI 0.42 to 0.92
  • Placebo vs Prochieve · Cochran-Mantel-Haenszel · p = 0.376 · Risk ratio (rr): 0.89 · 95% CI 0.68 to 1.16
SecondaryNumber of Neonates Who Died.
Time frame:
Delivery to 28 days
Reported as:
Number · participants
Number of Neonates Who Died.
participantsPlaceboProchieve
Number of Neonates Who Died.53
Statistical analysis
  • Placebo vs Prochieve · Cochran-Mantel-Haenszel · p = 0.431 · Risk ratio (rr): 0.57 · 95% CI 0.14 to 2.35
SecondaryNumber of Infants With a Birth Weight < 1500 Grams or < 2500 Grams

Assessment of birth weight \< 1500 grams or \< 2500 grams

Time frame:
date of delivery
Reported as:
Number · participants
Number of Infants With a Birth Weight < 1500 Grams or < 2500 Grams
participantsPlaceboProchieve
Birth weight < 1500 grams3015
Birth weight < 2500 grams6860
Statistical analysis
  • Placebo vs Prochieve · Cochran-Mantel-Haenszel · p = 0.01 · Risk ratio (rr): 0.47 · 95% CI 0.26 to 0.85
  • Placebo vs Prochieve · Cochran-Mantel-Haenszel · p = 0.213 · Risk ratio (rr): 0.83 · 95% CI 0.62 to 1.11

Adverse events

Collected over Randomization to delivery (1 day to 168 days). Non-serious events are listed at a 0.5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—98/224 (43.8%)24/223 (10.8%)
Prochieve—97/235 (41.3%)30/235 (12.8%)
Most frequent serious events
Showing 10 of 56
Most frequent serious events
EventPlaceboProchieve
premature babyPregnancy, puerperium and perinatal conditions46/22444/235
premature laborPregnancy, puerperium and perinatal conditions33/22417/235
cervix disorderReproductive system and breast disorders12/22421/235
premature rupture of the membranesPregnancy, puerperium and perinatal conditions9/22412/235
cervix cerclage procedureSurgical and medical procedures5/2249/235
uterine contractions abnormalPregnancy, puerperium and perinatal conditions7/2245/235
foetal distress abnormalPregnancy, puerperium and perinatal conditions3/2246/235
pre-eclampsiaPregnancy, puerperium and perinatal conditions4/2242/235
foetal growth retardationPregnancy, puerperium and perinatal conditions4/2241/235
premature separation of placentaPregnancy, puerperium and perinatal conditions4/2241/235
Most frequent other events
Showing 10 of 17
Most frequent other events
EventPlaceboProchieve
NauseaGastrointestinal disorders23/22323/235
cervix disorderReproductive system and breast disorders17/22323/235
HeadacheNervous system disorders18/22316/235
Vulvovaginal mycotic infectionInfections and infestations11/22317/235
DyspepsiaGastrointestinal disorders12/22315/235
Vaginal infectionReproductive system and breast disorders11/22315/235
anaemiaBlood and lymphatic system disorders14/22315/235
Bleeding peripartumPregnancy, puerperium and perinatal conditions14/2239/235
gestational diabetesMetabolism and nutrition disorders9/22314/235
abdominal painGastrointestinal disorders11/22313/235

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)PlaceboProchieveTotal
<=18 years000
Between 18 and 65 years223235458
>=65 years000
Age Continuous
Age Continuous(years)PlaceboProchieveTotal
Mean26.2 ± 5.126.5 ± 5.826.4 ± 5.5
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboProchieveTotal
Female223235458
Male000
Region of Enrollment
Region of Enrollment(participants)PlaceboProchieveTotal
Belarus7512
United States100107207
Czech Republic134
Ukraine262854
South Africa111021
Russian Federation011
Israel033
Chile202
Italy358
India7373146
08

Study locations

49 sites
  • University of South Alabama Dept. of OB/GYN
    Mobile, Alabama 36604, United States
  • St. Joseph's Hospital and Med Ctr Women's Care Center
    Phoenix, Arizona 85013, United States
  • UCI Medical Center
    Orange, California 92868, United States
  • Harbor-UCLA Medical Center
    Torrance, California 90502, United States
  • University of Miami Leonard Miller School of Medicine Department of Obstetrics and Gynecology
    Miami, Florida 33101, United States
  • Kapi'olani Medical Center for Women and Children
    Honolulu, Hawaii 96826, United States
  • Perinatal Center of Iowa
    Des Moines, Iowa 50314, United States
  • University of Kansas Medical Center
    Kansas City, Kansas 66160, United States
  • Perinatal Diagnostic Center
    Lexington, Kentucky 40503, United States
  • Johns Hopkins Community Physicians
    Baltimore, Maryland 21211, United States
  • Caritas St. Elizabeth's Medical Center
    Boston, Massachusetts 02135, United States
  • Perinatology Research Branch Hutzel Women's Hospital
    Detroit, Michigan 48201, United States
  • Henry Ford Healthcare System
    Detroit, Michigan 48202, United States
  • Spectrum Health Research Department
    Grand Rapids, Michigan 49503, United States
  • St. Joseph Mercy-Oakland
    Pontiac, Michigan 48341, United States
  • Washington University School of Medicine, Dept. of OB/GYN
    St. Louis, Missouri 63110, United States
  • St. Louis University Health Sciences Center
    St. Louis, Missouri 63117, United States
  • Cooper University Hospital
    Camden, New Jersey 08103, United States
  • Albert Einstein Hospital
    Bronx, New York 10461, United States
  • Winthrop University Hosital
    Mineola, New York 11501, United States
  • Lyndhurst Clinical Research
    Winston-Salem, North Carolina 27103, United States
  • UPHS Pennsylvania Hospital
    Philadelphia, Pennsylvania 19107-6130, United States
  • Thomas Jefferson University Hospital OB/GYN / Maternal Fetal Medicine
    Philadelphia, Pennsylvania 19107, United States
  • Regional Obstetrical Consultants, Chattanooga
    Chattanooga, Tennessee 37403, United States
  • Regional Obstetrical Consultants, Knoxville
    Knoxville, Tennessee 37920, United States
  • Eastern Virginia Medical School
    Norfolk, Virginia 23507, United States
  • Charleston Area Medical Center Clinical Trials Center
    Charleston, West Virginia 25304, United States
  • 1st Clinical Hospital of the City of Minsk
    Minsk, 22004, Belarus
  • Public Health Services Establishment "Vitebsk City Clinical Hospital of First Aid"
    Vitebsk, 210009, Belarus
  • Escuela De Medicina, Pontificia Universidad Catolica De Chile
    Santiago, Chile
  • Maternidad Hospital DR Sotero Del Rio
    Santiago, Chile
  • Charles University & General Teaching Hospital
    Prague, Czech Republic
  • BJ Medical College & Sassoon Hospital
    Pune, Maharashtra 411001, India
  • Sri Ramchandra Medical College and Research Institute
    Porur, Tamil Nadu 600003, India
  • Sheth L.G. Hospital
    Ahmedabad, 380008, India
  • MediCiti Institute of Medical Sciences
    Andhra Pradesh, 5014, India
  • Government Medical College
    Nagpur, 440003, India
  • Soroka University Medical Center
    Beer-Sheva, 84965, Israel
  • Kaplan Medical Center
    Rehovot, 76100, Israel
  • Sheba Medical Center
    Tel Hashomer, 58291, Israel
  • Azienda Ospedaliera di Padova Centro Prenatale Divisione di Ostetricia
    Padova, 35128, Italy
  • Limited Liability Company "American Health Clinic"
    Saint Petersburg, 190000, Russian Federation
  • Saint Petersburg State Healthcare Institution Maternity Hospital 17
    Saint Petersburg, 192174, Russian Federation
  • Steve Biko Academic Hospital Dept. of OB-GYN and Maternal Fetal Medicine
    Pretoria, 0001, South Africa
  • Municipal health care establishment "City Maternity Clinical Hospital"
    Chernovtsy, 58001, Ukraine
  • Department of Obstetrics and Gynecology of Dnepropetrovsk State Medical Academy, Municipal establishment "City Maternity Hospital # 1"
    Dnepropetrovsk, 49000, Ukraine
  • M. Gorky Donetsk National Medical University, Department of Obstetrics, Gynecology and Perinatology, Maternity Hospital of 6th Central City Clinical Hospital
    Donetsk, 83062, Ukraine
  • Municipal clinical hospital #1
    Kiev, 2175, Ukraine
  • Antenatal Clinic # 1, Central Polyclinics of Pechersk District
    Kyiv, 01042, Ukraine
09

References and documents

Publications

  • O'Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, Soma-Pillay P, Porter K, How H, Schackis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007 Oct;30(5):687-96. doi: 10.1002/uog.5158. PubMed 17899572 ↗
  • DeFranco EA, O'Brien JM, Adair CD, Lewis DF, Hall DR, Fusey S, Soma-Pillay P, Porter K, How H, Schakis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW. Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007 Oct;30(5):697-705. doi: 10.1002/uog.5159. PubMed 17899571 ↗
  • Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007 Aug 2;357(5):462-9. doi: 10.1056/NEJMoa067815. PubMed 17671254 ↗
  • Romero R. Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment. Ultrasound Obstet Gynecol. 2007 Oct;30(5):675-86. doi: 10.1002/uog.5174. No abstract available. PubMed 17899585 ↗
  • Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, Vijayaraghavan J, Trivedi Y, Soma-Pillay P, Sambarey P, Dayal A, Potapov V, O'Brien J, Astakhov V, Yuzko O, Kinzler W, Dattel B, Sehdev H, Mazheika L, Manchulenko D, Gervasi MT, Sullivan L, Conde-Agudelo A, Phillips JA, Creasy GW; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31. doi: 10.1002/uog.9017. Epub 2011 Jun 15. PubMed 21472815 ↗
  • Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Klein K, Rode L, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol. 2012 Feb;206(2):124.e1-19. doi: 10.1016/j.ajog.2011.12.003. Epub 2011 Dec 11. PubMed 22284156 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 13, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00615550
Lead sponsor
Juniper Pharmaceuticals, Inc.
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party
Sponsor
First posted
Feb 14, 2008
Start date
Mar 2008
Primary completion
Nov 2010
Completion
Nov 2010
Results posted
Mar 13, 2012
Last update
Mar 13, 2012

Study contacts

George W. Creasy, MD, FACOG
study director · Columbia Laboratories, Inc.
Roberto Romero, MD
study director · Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sonia Hassan, MD
study director · Wayne State University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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