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

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ClinicalTrials.gov Identifier: NCT02518594
Recruitment Status : Recruiting
First Posted : August 10, 2015
Last Update Posted : July 20, 2020
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

Tracking Information
First Submitted Date  ICMJE March 18, 2015
First Posted Date  ICMJE August 10, 2015
Last Update Posted Date July 20, 2020
Actual Study Start Date  ICMJE November 13, 2015
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2015)
Delivery prior to 35 weeks or fetal loss [ Time Frame: prior to 35 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2015)
  • 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
  • Gestational age at delivery [ Time Frame: 16 to 42 weeks ]
  • Neonatal morbidity and mortality [ Time Frame: 16 to 42 weeks ]
  • Lower genital tract or urinary tract infection [ Time Frame: 16 to 42 weeks ]
  • Physician interventions [ Time Frame: 16 to 42 weeks ]
    Composite measure. Includes bedrest, cerclage, labor inhibition therapy.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix
Official Title  ICMJE A Randomized Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Short Cervical Length
Intervention  ICMJE
  • Drug: Vaginal progesterone
    200mg micronized vaginal progesterone softgel capsule, daily from randomization to < 35 wks
    Other Name: Prometrium
  • Drug: Placebo
    placebo softgel capsule, daily from randomization to < 35 wks
  • Device: Arabin Pessary
    Placement management from randomization to < 35 wks
Study Arms  ICMJE
  • Active Comparator: Progesterone
    200mg micronized vaginal progesterone softgel capsule, daily from randomization to < 35 wks
    Intervention: Drug: Vaginal progesterone
  • Placebo Comparator: Placebo
    placebo softgel capsule, daily from randomization to < 35 wks
    Intervention: Drug: Placebo
  • Active Comparator: Arabin Pessary
    placement management from randomization to < 35 wks
    Intervention: Device: Arabin Pessary
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 16, 2017)
630
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2015)
600
Estimated Study Completion Date  ICMJE February 2025
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rebecca Clifton, PhD 301-881-9260 rclifton@bsc.gwu.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02518594
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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.
Responsible Party The George Washington University Biostatistics Center
Study Sponsor  ICMJE The George Washington University Biostatistics Center
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Study Chair: Joseph Biggio, MD Maternal Fetal Medicine Units (MFMU) Network
Study Director: Andrew Bremer, M.D., PhD, MAS Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
PRS Account The George Washington University Biostatistics Center
Verification Date July 2020

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