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 |
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Recruitment Status :
Recruiting
First Posted : August 10, 2015
Last Update Posted : December 5, 2018
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Sponsor:
The George Washington University Biostatistics Center
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The George Washington University Biostatistics Center
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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 |
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
Drug Information available for:
Progesterone
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Progesterone
200mg micronized vaginal progesterone softgel capsule, daily from randomization to < 35 wks
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Drug: Vaginal progesterone
200mg micronized vaginal progesterone softgel capsule, daily from randomization to < 35 wks
Other Name: Prometrium |
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Placebo Comparator: Placebo
placebo softgel capsule, daily from randomization to < 35 wks
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Drug: Placebo
placebo softgel capsule, daily from randomization to < 35 wks |
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Active Comparator: Arabin Pessary
placement management from randomization to < 35 wks
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Device: Arabin Pessary
Placement management from randomization to < 35 wks |
Primary Outcome Measures :
- 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 :
- 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.
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
- Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
- Cervical length on transvaginal examination of less than 30 mm within 10 days prior to randomization by a study certified sonographer.
Exclusion Criteria:
- 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.
- Monoamniotic gestation, due to increased risk of adverse pregnancy outcome
- Twin-twin transfusion syndrome, due to increased risk of adverse pregnancy outcome
- Evidence of severe IUGR (intrauterine growth restriction) (<5th percentile for gestational age) in either fetus
- 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.
- Placenta previa, because of risk of bleeding and high potential for indicated preterm birth
- Active vaginal bleeding greater than spotting at the time of randomization, because of potential exacerbation due to pessary placement.
- Symptomatic, untreated vaginal or cervical infection, also because of potential exacerbation due to pessary placement. Patients may be treated and if subsequently asymptomatic, randomized.
- 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.
- 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
- More than six contractions per hour reported or documented prior to randomization. It is not necessary to place the patient on a tocodynamometer
- 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
- Any fetal/maternal condition which would require invasive in-utero assessment or treatment, for example significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia
- 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.
- Planned cerclage or cerclage already in place since it would preclude placement of a pessary
- Planned indicated delivery prior to 35 weeks
- Planned or actual progesterone treatment of any type or form after 14 weeks 6 days during the current pregnancy
- Allergy to progesterone, silicone, or excipients in the study drug, including peanuts or peanut oil in the study drug or placebo
- Known, suspected or history of breast cancer because breast cancer is a contraindication to the active study medication.
- Known liver dysfunction or disease because liver disease is a contraindication to the active study medication.
- Participation in another interventional study that influences gestational age at delivery or neonatal morbidity or mortality
- 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.
- 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 |
Keywords provided by The George Washington University Biostatistics Center:
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women cervical length of less than 30 millimeters carrying twins short cervix |
Additional relevant MeSH terms:
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Progesterone Progestins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |