ClinicalTrials.gov
ClinicalTrials.gov Menu

A Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix (PROSPECT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02518594
Recruitment Status : Recruiting
First Posted : August 10, 2015
Last Update Posted : December 5, 2018
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The George Washington University Biostatistics Center

Brief Summary:
This protocol outlines a randomized trial of 630 women evaluating the use of micronized vaginal progesterone or pessary versus control (placebo) to prevent early preterm birth in women carrying twins and with a cervical length of less than 30 millimeters.

Condition or disease Intervention/treatment Phase
Short Cervical Length Drug: Vaginal progesterone Drug: Placebo Device: Arabin Pessary Phase 3

Detailed Description:

This protocol outlines a randomized trial of 630 women evaluating the use of micronized vaginal progesterone or pessary versus control (placebo) to prevent early preterm birth in women carrying twins and with a cervical length of less than 30 millimeters.

Multiple gestation increases the risk of preterm delivery. Babies born preterm have increased rates of neonatal mortality and long-term neurodevelopmental morbidities. Short cervical length is known to be an important risk factor for spontaneous preterm birth and to occur more frequently in women with a twin gestation. Although there is no evidence that progesterone reduces the risk of preterm birth in multifetal gestation, there is evidence that progesterone reduces the risk of prematurity in singleton gestations complicated with a short cervix. The Arabin pessary has also been shown to reduce the risk of preterm birth among singletons with a short cervix, and in a secondary subgroup analysis of a recent study of the use of pessary in multiple gestations, women with a cervical length < 25th percentile had a significantly reduced risk of the primary composite neonatal adverse outcome. Secondary analysis of studies of vaginal progesterone in multiple gestation with a short cervix also suggest a possible beneficial effect on preterm delivery.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 630 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Women will be randomly assigned to study drug (200 mg micronized progesterone daily), placebo study drug appearing identical to progesterone capsule, or Arabin pessary.
Masking: Double (Participant, Care Provider)
Masking Description: Participants and care providers will be blinded to active study drug vs. placebo.
Primary Purpose: Treatment
Official Title: A Randomized Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix
Actual Study Start Date : November 13, 2015
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Progesterone
200mg micronized vaginal progesterone softgel capsule, daily from randomization to < 35 wks
Drug: Vaginal progesterone
200mg micronized vaginal progesterone softgel capsule, daily from randomization to < 35 wks
Other Name: Prometrium

Placebo Comparator: Placebo
placebo softgel capsule, daily from randomization to < 35 wks
Drug: Placebo
placebo softgel capsule, daily from randomization to < 35 wks

Active Comparator: Arabin Pessary
placement management from randomization to < 35 wks
Device: Arabin Pessary
Placement management from randomization to < 35 wks




Primary Outcome Measures :
  1. Delivery prior to 35 weeks or fetal loss [ Time Frame: prior to 35 weeks ]
    Delivery of the infant before 35 weeks gestation or loss of the fetus.


Secondary Outcome Measures :
  1. Randomization to delivery interval [ Time Frame: 16 to 42 weeks ]
    Randomization may begin at 16 weeks, and most patients will be delivered by 41 weeks

  2. Gestational age at delivery [ Time Frame: 16 to 42 weeks ]
  3. Neonatal morbidity and mortality [ Time Frame: 16 to 42 weeks ]
  4. Lower genital tract or urinary tract infection [ Time Frame: 16 to 42 weeks ]
  5. Physician interventions [ Time Frame: 16 to 42 weeks ]
    Composite measure. Includes bedrest, cerclage, labor inhibition therapy.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Twin gestation with cardiac activity in both fetuses. Higher order multifetal gestations reduced to twins, either spontaneously or therapeutically, are not eligible unless the reduction occurred by 13 weeks 6 days project gestational age.
  2. Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
  3. Cervical length on transvaginal examination of less than 30 mm within 10 days prior to randomization by a study certified sonographer.

Exclusion Criteria:

  1. Cervical dilation (internal os) 3 cm or greater on digital examination or evidence of prolapsed membranes beyond the external cervical os either at the time of the qualifying cervical ultrasound examination or at a cervical exam immediately before randomization. There is no lower threshold of cervical length measurement threshold on ultrasound that is an exclusion criterion.
  2. Monoamniotic gestation, due to increased risk of adverse pregnancy outcome
  3. Twin-twin transfusion syndrome, due to increased risk of adverse pregnancy outcome
  4. Evidence of severe IUGR (intrauterine growth restriction) (<5th percentile for gestational age) in either fetus
  5. Fetal anomaly in either twin or imminent fetal demise. This includes lethal anomalies, or anomalies that may lead to early delivery or increased risk of neonatal death e.g., gastroschisis, spina bifida, serious karyotypic abnormalities). An ultrasound examination from 14 weeks 0 days to 23 weeks 6 days by project EDC (estimated date of conception) must be performed prior to randomization to evaluate the fetuses for anomalies.
  6. Placenta previa, because of risk of bleeding and high potential for indicated preterm birth
  7. Active vaginal bleeding greater than spotting at the time of randomization, because of potential exacerbation due to pessary placement.
  8. Symptomatic, untreated vaginal or cervical infection, also because of potential exacerbation due to pessary placement. Patients may be treated and if subsequently asymptomatic, randomized.
  9. Active, unhealed herpetic lesion on labia minora, vagina, or cervix due to the potential for significant patient discomfort or increasing genital tract viral spread. Once lesion(s) heal and the patient is asymptomatic, she may be randomized. History of herpes is not an exclusion.
  10. Rupture of membranes due to likelihood of pregnancy loss and preterm delivery as well as the risk of ascending infection which could be increased with pessary placement
  11. More than six contractions per hour reported or documented prior to randomization. It is not necessary to place the patient on a tocodynamometer
  12. Known major Mullerian anomaly of the uterus (specifically bicornuate, unicornuate, or uterine septum not resected) due to increased risk of preterm delivery which is unlikely to be affected by progesterone
  13. Any fetal/maternal condition which would require invasive in-utero assessment or treatment, for example significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia
  14. Major maternal medical illness associated with increased risk for adverse pregnancy outcome or indicated preterm birth (treated hypertension requiring more than one agent, pre-gestational treatment for diabetes prior to pregnancy, chronic renal insufficiency failure defined by creatinine >1.4 mg/dL, carcinoma of the breast, conditions treated with chronic oral glucocorticoid therapy. Specifically, patients with seizure disorders, HIV, and other medical conditions not specifically associated with an increased risk of indicated preterm birth are not excluded. Prior cervical cone/LOOP/LEEP is not an exclusion criterion.
  15. Planned cerclage or cerclage already in place since it would preclude placement of a pessary
  16. Planned indicated delivery prior to 35 weeks
  17. Planned or actual progesterone treatment of any type or form after 14 weeks 6 days during the current pregnancy
  18. Allergy to progesterone, silicone, or excipients in the study drug, including peanuts or peanut oil in the study drug or placebo
  19. Known, suspected or history of breast cancer because breast cancer is a contraindication to the active study medication.
  20. Known liver dysfunction or disease because liver disease is a contraindication to the active study medication.
  21. Participation in another interventional study that influences gestational age at delivery or neonatal morbidity or mortality
  22. Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, do not have to be excluded.
  23. Prenatal care or delivery planned elsewhere unless the study visits can be made as scheduled and complete outcome information can be obtained

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02518594


Contacts
Contact: Uma Reddy, MD, MPH 301-496-1074 reddyu@mail.nih.gov
Contact: Elizabeth Thom, PhD 301-881-9260 e_thom@bsc.gwu.edu

Locations
United States, Alabama
University of Alabama - Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Stacy Harris, RN BSN    205-934-1322    stacylharris@uabmc.edu   
Principal Investigator: Alan TN Tita, MD         
United States, Colorado
University of Colorado Active, not recruiting
Denver, Colorado, United States, 80045
United States, Illinois
Northwestern University-Prentice Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Gail Mallett    312-503-3200    g-mallett@northwestern.edu   
Principal Investigator: William Grobman, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Sabine Bousleiman    212-305-4348    sb1080@columbia.edu   
Principal Investigator: Cynthia Gyamfi-Bannerman, MD         
United States, North Carolina
University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Kelly Clark, RN    919-350-6117    kelly_clark@med.unc.edu   
Principal Investigator: John M Thorp, Jr., MD         
Duke University Active, not recruiting
Durham, North Carolina, United States, 27710
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44109
Contact: Wendy Dalton, RNC    216-778-7533    wdalton@metrohealth.org   
Principal Investigator: Edward Chien, MD         
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Anna Bartholomew, RN, BSN    614-685-3229    anna.bartholomew@osumc.edu   
Principal Investigator: Catalin S Buhimschi, MD         
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Mary Hammond, BSN, RN    215-662-2657    mary.hammond@uphs.upenn.edu   
Principal Investigator: Samuel Parry, MD         
Magee Women's Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Melissa Bickus, BS, RN    412-641-4072    mbickus@mail.magee.edu   
Principal Investigator: Hyagriv Simhan, MD, MS         
United States, Rhode Island
Brown University Recruiting
Providence, Rhode Island, United States, 02905
Contact: Donna Allard, RNC    401-274-1122 ext 8522    dallard@wihri.org   
Principal Investigator: Dwight Rouse, MD         
United States, Texas
University of Texas - Galveston Recruiting
Galveston, Texas, United States, 77555
Contact: Ashley Salazar, RN MSN WHNP    409-772-0312    assalaza@utmb.edu   
Principal Investigator: George Saade, MD         
University of Texas - Houston Recruiting
Houston, Texas, United States, 77030
Contact: Felecia Ortiz, RN    713-500-6467    Felecia.Ortiz@uth.tmc.edu   
Principal Investigator: Suneet Chauhan, MD         
United States, Utah
University of Utah Medical Center Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Kim Hill, RN BSN    801-585-5586    Kim.Hill@hsc.utah.edu   
Principal Investigator: Michael W Varner, MD         
Sponsors and Collaborators
The George Washington University Biostatistics Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Study Chair: Joseph Biggio, MD Maternal Fetal Medicine Units (MFMU) Network

Responsible Party: The George Washington University Biostatistics Center
ClinicalTrials.gov Identifier: NCT02518594     History of Changes
Other Study ID Numbers: HD36801-PROSPECT
U10HD036801 ( U.S. NIH Grant/Contract )
UG1HD087230 ( U.S. NIH Grant/Contract )
UG1HD027869 ( U.S. NIH Grant/Contract )
UG1HD027915 ( U.S. NIH Grant/Contract )
UG1HD034208 ( U.S. NIH Grant/Contract )
UG1HD040500 ( U.S. NIH Grant/Contract )
UG1HD040485 ( U.S. NIH Grant/Contract )
UG1HD053097 ( U.S. NIH Grant/Contract )
UG1HD040544 ( U.S. NIH Grant/Contract )
UG1HD040545 ( U.S. NIH Grant/Contract )
UG1HD040560 ( U.S. NIH Grant/Contract )
UG1HD040512 ( U.S. NIH Grant/Contract )
UG1HD087192 ( U.S. NIH Grant/Contract )
UG1HD068282 ( U.S. NIH Grant/Contract )
UG1HD068258 ( U.S. NIH Grant/Contract )
UG1HD068268 ( U.S. NIH Grant/Contract )
First Posted: August 10, 2015    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The dataset will be shared per NIH policy after the completion and publication of the main analyses. Requests for datasets can be sent to mfmudatasets@bsc.gwu.edu.

Keywords provided by The George Washington University Biostatistics Center:
women
cervical length of less than 30 millimeters
carrying twins
short cervix

Additional relevant MeSH terms:
Progesterone
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs