- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02518594
A Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix (PROSPECT)
A Randomized Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Rebecca Clifton, PhD
- Phone Number: 301-881-9260
- Email: rclifton@bsc.gwu.edu
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294
- Recruiting
- University of Alabama - Birmingham
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Contact:
- Jeannette Boyce, RN
- Phone Number: 412-527-8118
- Email: tessje@upmc.edu
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Principal Investigator:
- Alan TN Tita, MD
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California
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San Francisco, California, United States
- Recruiting
- The Regents of the University of California, San Francisco
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Principal Investigator:
- Mary Norton, MD
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Contact:
- Natalie Oman, MPH
- Phone Number: 206-718-4703
- Email: natalie.oman@ucsf.edu
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Colorado
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Denver, Colorado, United States, 80045
- Active, not recruiting
- University of Colorado
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Illinois
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Chicago, Illinois, United States, 60611
- Recruiting
- Northwestern University-Prentice Hospital
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Contact:
- Gail Mallett
- Phone Number: 312-503-3200
- Email: g-mallett@northwestern.edu
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Principal Investigator:
- Lynn Yee, MD, MPH
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New York
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New York, New York, United States, 10032
- Recruiting
- Columbia University
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Contact:
- Sabine Bousleiman
- Phone Number: 212-305-4348
- Email: sb1080@columbia.edu
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Principal Investigator:
- Uma Reddy, MD
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- Recruiting
- University of North Carolina - Chapel Hill
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Contact:
- Kelly Clark, RN
- Phone Number: 919-350-6117
- Email: kelly_clark@med.unc.edu
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Principal Investigator:
- John M Thorp, Jr., MD
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Durham, North Carolina, United States, 27710
- Recruiting
- Duke University
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Principal Investigator:
- Geeta K Swamy, MD
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Contact:
- Jennifer Ferrara, RNC MSN
- Phone Number: 919-681-6176
- Email: jennifer.ferrara@duke.edu
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Ohio
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Cleveland, Ohio, United States, 44109
- Recruiting
- Case Western Reserve University
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Principal Investigator:
- Kelly Gibson, MD
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Contact:
- Abigail Pierse, BS
- Phone Number: 216-778-8443
- Email: apierse@metrohealth.org
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Columbus, Ohio, United States, 43210
- Recruiting
- Ohio State University
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Principal Investigator:
- Maged Costantine, MD
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Contact:
- Anna Bartholomew, RN, BSN
- Phone Number: 614-685-3229
- Email: anna.bartholomew@osumc.edu
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Recruiting
- Hospital of the University of Pennsylvania
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Principal Investigator:
- Samuel Parry, MD
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Contact:
- Christina Pizzi, RN
- Phone Number: 267-273-8574
- Email: christina.pizzi@pennmedicine.upenn.edu
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Pittsburgh, Pennsylvania, United States, 15213
- Recruiting
- Magee Women's Hospital
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Contact:
- Jeanette Boyce, RN
- Phone Number: 412-527-8118
- Email: tessje@upmc.edu
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Principal Investigator:
- Hyagriv Simhan, MD, MS
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Rhode Island
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Providence, Rhode Island, United States, 02905
- Recruiting
- Brown University
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Principal Investigator:
- Dwight Rouse, MD
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Contact:
- Angelica DeMartino, RN, BSN
- Phone Number: 48521 401-274-1122
- Email: amdemartino@wihri.org
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Texas
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Galveston, Texas, United States, 77555
- Recruiting
- University of Texas - Galveston
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Contact:
- Amelia Nounes, MSN, RN
- Phone Number: 409-747-1758
- Email: aanounes@utmb.edu
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Principal Investigator:
- Luis Pacheco, MD
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Houston, Texas, United States
- Recruiting
- Baylor College of Medicine
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Contact:
- Christine Reed, RN
- Phone Number: 832-826-7377
- Email: Christina.Reed@bcm.edu
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Contact:
- Jia Chen, RN
- Phone Number: 713-798-3798
- Email: Jia.Chen@bcm.edu
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Principal Investigator:
- Catherine Eppes, MD, MPH
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Houston, Texas, United States, 77030
- Recruiting
- University of Texas - Houston
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Principal Investigator:
- Hector Mendez-Figueroa, MD
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Contact:
- Felecia Ortiz, RN
- Phone Number: 713-500-6467
- Email: Felecia.Ortiz@uth.tmc.edu
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Utah
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Salt Lake City, Utah, United States, 84132
- Recruiting
- University of Utah Medical Center
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Contact:
- Amber Sowles, RN BSN
- Phone Number: 801-585-5499
- Email: amber.sowles@hsc.utah.edu
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Principal Investigator:
- Torri Metz, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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 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 15 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Progesterone
200mg micronized vaginal progesterone softgel capsule, daily from randomization to < 35 wks
|
200mg micronized vaginal progesterone softgel capsule, daily from randomization to < 35 wks
Other Names:
|
Placebo Comparator: Placebo
placebo softgel capsule, daily from randomization to < 35 wks
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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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Placement management from randomization to < 35 wks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Delivery or fetal loss of either twin prior to 35 weeks gestation
Time Frame: prior to 35 weeks gestation
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Preterm delivery or fetal loss prior to 35 weeks gestation
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prior to 35 weeks gestation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Interval from randomization to delivery (or fetal demise)
Time Frame: Randomization to delivery can be up to 26 weeks
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Randomization may begin at 16 weeks, and most patients will be delivered by 41 weeks
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Randomization to delivery can be up to 26 weeks
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Gestational age at delivery
Time Frame: Randomization to delivery can be up to 26 weeks
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Gestational age at the time of delivery.
Randomization begins at 16 weeks gestation
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Randomization to delivery can be up to 26 weeks
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Preterm delivery or fetal demise of either twin prior to 28 weeks gestation, 32 weeks gestation, and 37 weeks gestation
Time Frame: From randomization to up to 37 weeks gestation (up to 21 weeks)
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Preterm delivery or fetal loss of either twin prior to 28 weeks gestation; prior to 32 weeks gestation; and prior to 37 weeks gestation
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From randomization to up to 37 weeks gestation (up to 21 weeks)
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Spontaneous preterm delivery (following preterm labor or pPROM) < 35 weeks gestation and < 32 weeks gestation
Time Frame: From randomization to delivery (up to 19 weeks)
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Spontaneous preterm delivery before 35 weeks gestation and 32 weeks gestation
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From randomization to delivery (up to 19 weeks)
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Indicated preterm delivery < 35 weeks
Time Frame: From randomization to delivery (up to 19 weeks)
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Preterm delivery prior to 35 weeks gestation with medical indications
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From randomization to delivery (up to 19 weeks)
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Cesarean delivery
Time Frame: Randomization to delivery can be up to 26 weeks
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Delivery by cesarean
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Randomization to delivery can be up to 26 weeks
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Fetal or neonatal death
Time Frame: Up to 28 days postnatal age
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Fetal or neonatal death
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Up to 28 days postnatal age
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Small for gestational age
Time Frame: Randomization to delivery can be up to 26 weeks
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Less than 5th percentile weight for gestational age, by sex and race of the infant based on United States birth certificate data
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Randomization to delivery can be up to 26 weeks
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Composite neonatal outcome
Time Frame: Birth to neonatal discharge or death, whichever is first (up to 6 weeks)
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Fetal or neonatal death, RDS, grade III or IV IVH, PVL, Stage 2 or 3 NEC, BPD, Stage III or higher ROP, or early onset sepsis
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Birth to neonatal discharge or death, whichever is first (up to 6 weeks)
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Length of hospital stay, need for NICU or intermediate care admission and length of stay if admitted
Time Frame: Birth to neonatal discharge or death, whichever is first (up to 6 weeks)
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Length of hospital stay in days, any Neonatal ICU or intermediate care admission, or length of hospital or intermediate care stay in days
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Birth to neonatal discharge or death, whichever is first (up to 6 weeks)
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Collaborators and Investigators
Collaborators
Investigators
- Study Director: Monica Longo, MD, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study Chair: Joseph Biggio, MD, Maternal Fetal Medicine Units (MFMU) Network
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HD36801-PROSPECT
- UG1HD087230 (U.S. NIH Grant/Contract)
- UG1HD027869 (U.S. NIH Grant/Contract)
- UG1HD040500 (U.S. NIH Grant/Contract)
- UG1HD034208 (U.S. NIH Grant/Contract)
- UG1HD027915 (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)
- U24HD036801 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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