Preterm Erythropoietin Neuroprotection Trial (PENUT Trial)



Status:Active, not recruiting
Healthy:No
Age Range:Any
Updated:9/21/2018
Start Date:December 2013
End Date:December 31, 2018

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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.

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.

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
We found this trial at
19
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Gainesville, Florida 32610
(352) 392-3261
Principal Investigator: Michael Weiss, MD
University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
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Little Rock, Arkansas 72202
Principal Investigator: Sherry Courtney, MD
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201 Presidents Circle
Salt Lake City, Utah 84108
801) 581-7200
Principal Investigator: Mariana Baserga, MD
University of Utah Research is a major component in the life of the U benefiting...
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Seattle, Washington 98104
(206) 543-2100
Principal Investigator: Dennis E Mayock, MD
Univ of Washington Founded in 1861 by a private gift of 10 acres in what...
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Albuquerque, New Mexico 87131
Principal Investigator: Robin Ohls, MD
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Baltimore, Maryland 21218
(410) 516-8000
Principal Investigator: Maureen Gilmore, MD
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Boston, Massachusetts 02215
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Chicago, Illinois 60611
Principal Investigator: Janine Khan, MD
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Chicago, Illinois 60612
Principal Investigator: Sachin Amin, MD
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500 S Preston St
Louisville, Kentucky
(502) 852-5555
Principal Investigator: Tonya Ronbinson, MD
University of Louisville The University of Louisville is a state supported research university located in...
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3100 Southwest 62nd Avenue
Miami, Florida 33143
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Minneapolis, Minnesota 55404
Principal Investigator: Ellen Bendel-Stenzel, MD
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Minneapolis, Minnesota 55455
Principal Investigator: Raghavendra Rao, MD
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601 E Rollins St
Orlando, Florida 32803
(407) 303-5600
Principal Investigator: Rajan Wadhawan, MD
Florida Hospital Florida Hospital is one of the country
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345 Smith Avenue North
Saint Paul, Minnesota 55102
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Saint Petersburg, Florida 33701
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San antonio, Texas 78229
Principal Investigator: Kaashif Ahmad, MD
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Valhalla, New York 10595
Principal Investigator: Edmund LaGamma, MD
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Winston-Salem, North Carolina 27157
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