Preterm Erythropoietin Neuroprotection Trial (PENUT Trial)
This trial is active, not recruiting.
|Sponsor||University of Washington|
|Collaborator||National Institute of Neurological Disorders and Stroke (NINDS)|
|Start date||December 2013|
|End date||November 2018|
|Trial size||941 participants|
|Trial identifier||NCT01378273, 41122-B|
Recombinant human erythropoietin (Epo) is a promising novel neuroprotective agent. Epo decreases neuronal programmed cell death resulting from brain injury; it has anti-inflammatory effects, increases neurogenesis, and protects oligodendrocytes from injury.
We hypothesize that neonatal Epo treatment of ELGANs will decrease the combined outcome of death or severe NDI from 40% to 30% (primary outcome), or the combined outcome of death plus moderate or severe NDI from 60% to 40% (secondary outcome) measured at 24-26 months corrected age.
1. To determine whether Epo decreases the combined outcome of death or NDI at 24-26 months corrected age. NDI is defined as the presence of any one of the following: CP, Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Scale < 70 (severe, 2 SD below mean) or 85 (moderate, 1 SD below mean). CP will be diagnosed and classified by standardized neurologic exam, with severity classified by Gross Motor Function Classification System (GMFCS).
2. To determine whether there are risks to Epo administration in ELGANs by examining, in a blinded manner, Epo-related safety measures comparing infants receiving Epo with those given placebo.
3. To test whether Epo treatment decreases serial measures of circulating inflammatory mediators, and biomarkers of brain injury.
4. To compare brain structure (as measured by MRI) in Epo treatment and control groups at 36 weeks PMA. MRI assessments will include documentation of intraventricular hemorrhage (IVH), white matter injury (WMI) and hydrocephalus (HC), volume of total and deep gray matter, white matter and cerebellum, brain gyrification, and tract-based spatial statistics (TBSS based on diffusion tensor imaging). As an exploratory aim, we will determine which of the above MRI measurements best predict neurodevelopment (CP, cognitive and motor scales) at 24-26 months corrected age.
Anticipated outcomes: Early Epo treatment of ELGANs will decrease biochemical and MRI markers of brain injury, will be safe, and will confer improved neurodevelopmental outcome at 24-26 months corrected age compared to placebo, and will provide a much-needed therapy for this group of vulnerable infants.
|United States||No locations recruiting|
|Other Countries||No locations recruiting|
|Little Rock, AR||University of Arkansas||no longer recruiting|
|Gainesville, FL||University of Florida||no longer recruiting|
|Orlando, FL||Florida Hospital||no longer recruiting|
|St Petersburg, FL||All Childrens Hospital||no longer recruiting|
|Chicago, IL||Prentice Women's Hospital||no longer recruiting|
|Chicago, IL||Children's Hospital of the University of Illinois||no longer recruiting|
|Louisville, KY||University of Louisville||no longer recruiting|
|Baltimore, MD||Johns Hopkins||no longer recruiting|
|Boston, MA||Beth Israel Deaconess Hospital||no longer recruiting|
|Minneapolis, MN||Children's Hospital of Minnesota, MN||no longer recruiting|
|Minneapolis, MN||University of Minnesota Amplatz Children's Hospital||no longer recruiting|
|St. Paul, MN||Children's Hospital of Minnesota, St. Paul||no longer recruiting|
|Albuquerque, NM||University of New Mexico Children's Hospital||no longer recruiting|
|Valhalla, NY||Maia Fareri Children's Hospital||no longer recruiting|
|Winston Salem, NC||Wake Forest School of Medicine||no longer recruiting|
|San antonio, TX||Methodist Children's Hospital||no longer recruiting|
|Salt Lake City, UT||University of Utah||no longer recruiting|
|Seattle, WA||University of Washington||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||parallel assignment|
|Masking||double blind (subject, caregiver, investigator, outcomes assessor)|
time frame: 24-26 months corrected age
time frame: term PMA
time frame: 24-26 months
time frame: 24-26 months of age
Male or female participants from 24 weeks up to 27 weeks old.
Inclusion Criteria: 1. NICU inpatients between 24-0/7 and 27-6/7 weeks of gestation 2. Less than twenty four hours of age 3. Parental informed consent Exclusion Criteria: 1. Major life-threatening anomalies (brain, cardiac, chromosomal anomalies) 2. Hematologic crises such as DIC, or hemolysis due to blood group incompatibilities 3. Polycythemia (hematocrit > 65) 4. Congenital infection
|Official title||Preterm Erythropoietin Neuroprotection Trial (PENUT Trial)|
|Principal investigator||Sandra E Juul, MD, PhD|
|Description||This is a randomized, placebo-controlled, study of Epo treatment of preterm infants 24-0/7 to 27-6/7 weeks of gestation, beginning in the first 24 hours after birth. Randomization will be stratified by site and gestational age at birth (<26 week or 26-27-6/7). Study size sample is 940 patients. We expect to evaluate 752 subjects at 24-26 months corrected age, our primary endpoint. There is no enrollment restriction based on gender, ethnicity or race. Enrollment is expected to take 24-26 months, with each subject participating through 24-26 months corrected age when neurodevelopmental outcomes are assessed. The combined outcome of death or severe NDI will be compared between Epo-treated and control subjects. All outcomes will be collected in a blinded manner. Subjects will be randomized by the data-coordinating center (DCC) to Epo treatment or placebo, and Epo treatment will continue until 32-6/7 weeks post menstrual age. Serial measurements of circulating inflammatory mediators and biomarkers of brain injury will be made. A brain MRI will be done at 36 weeks post menstrual age in the same subset of infants. Phone contact will occur at 4, 8, 12, and 18 months. Face to face follow up will occur at 24-26 months corrected age. The primary outcome is death or severe NDI at 24-26 months corrected age, with a secondary outcome of death or moderate NDI. Our primary sample size calculation is based on the conservative assumptions that Epo treatment will result in a 40% reduction in the severe NDI rate (the range in animal studies is 49-70%) and minimal impact on death. This would yield a control group rate for the primary outcome of 40.4% and an expected treated rate of 31.5% thus yielding an 8.9% lower rate of Death + NDI.|
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