Extreme PrematurityPhase 3PENUTNCT01378273
Preterm Erythropoietin Neuroprotection Trial (PENUT Trial)
A Phase 3 study testing Epo in people with Extreme Prematurity, run by University of Washington at 19 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 24 to 27 weeks
- Conditions the study is for
- Extreme Prematurity
- What is being tested?
- Epo
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 941 participants
- Where
- 19 sitesUnited States
- Study dates
- Dec 2013to 28 Feb 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 27 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- NICU inpatients between 24-0/7 and 27-6/7 weeks of gestation
- Less than twenty four hours of age
- Parental informed consent
Who cannot join
- Major life-threatening anomalies (brain, cardiac, chromosomal anomalies)
- Hematologic crises such as DIC, or hemolysis due to blood group incompatibilities
- Polycythemia (hematocrit > 65)
- Congenital infection
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
University of New Mexico Children's Hospital
Albuquerque, New Mexico, 87131
Johns Hopkins
Baltimore, Maryland, 21224
Beth Israel Deaconess Hospital
Boston, Massachusetts, 02215
Prentice Women's Hospital
Chicago, Illinois, 60611
Children's Hospital of the University of Illinois
Chicago, Illinois, 60612
University of Florida
Gainesville, Florida, 32610
University of Arkansas
Little Rock, Arkansas, 72202
University of Louisville
Louisville, Kentucky, 40202
South Miami Hospital
Miami, Florida, 33146
Children's Hospital of Minnesota, MN
Minneapolis, Minnesota, 55404
University of Minnesota Amplatz Children's Hospital
Minneapolis, Minnesota, 55455
Florida Hospital
Orlando, Florida, 32804
Children's Hospital of Minnesota, St. Paul
Saint Paul, Minnesota, 55102
University of Utah
Salt Lake City, Utah, 84108
Methodist Children's Hospital
San Antonio, Texas, 78229
University of Washington
Seattle, Washington, 98195
All Childrens Hospital
St. Petersburg, Florida, 33701
Maia Fareri Children's Hospital
Valhalla, New York, 10595
Wake Forest School of Medicine
Winston-Salem, North Carolina, 27157
About this study
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.
Read more
- 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).
- 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.
- To test whether Epo treatment decreases serial measures of circulating inflammatory mediators, and biomarkers of brain injury.
- 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.
Read the detailed 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.
Clinical information including co-morbidities of extreme prematurity, information about transfusions, and specific laboratory values were collected in the PENUT database.
- Conditions
- Extreme Prematurity
- Being tested
- Epo, Control
- Keywords
- neuroprotection, erythropoietin, Epo, ELGANs, preterm, neonate
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpoDrug
Also called Epotin, Erythropoietin
Enrollment will occur within 24 hours of birth. Study drug will be administered intravenously for the first 6 doses. Subjects in the Epo arm will then receive 400 U/kg/dose three times a week until they reach 32-6/7 weeks postmenstrual age. Control infants will receive sham injections.
ControlOther
Also called Saline
Subjects will receive 6 doses of vehicle intravenously during the first 2 weeks of life. Doses will be administered at 48 hour intervals from the time of enrollment. Following high dose administration, sham subcutaneous injections will be given three times a week through to 32-6/7 weeks postmenstrual age.
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Subjects will receive 6 doses of vehicle intravenously during the first 2 weeks of life. Doses will be administered at 48 hour intervals from the time of enrollment. Following high dose administration, sham subcutaneous injections will be given three times a week through to 32-6/7 weeks postmenstrual age. Receives: Other: Control |
| Epo 1000 U/kg followed by 400 U/kg | Experimental | Subjects will receive 6 doses of intravenous Epo 1000 U/kg/dose at 48 hour intervals from the time of enrollment. Following the high dose period, subjects will receive subcutaneous Epo 400 U/kg/dose three times a week until 32-6/7 weeks postmenstrual age. Receives: Drug: Epo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Death or Severe Neurodevelopmental Impairment (NDI) at 22-26 Months Corrected Age
Severe NDI was defined as Bayley Scales of infant Development, 3rd edition composite motor score or composite cognitive score <70. This instrument is normed at 100 with standard deviation of 15.
Cerebral palsy was classified as hemiplegia, diplegia, or quadriplegia, and severity was determined according to the Gross Motor Function Classification System (GMFCS) (levels range from 0 [no impairment] to 5 [most severe impairment]). Severe cerebral palsy was defined as a GMFCS level higher than 2.
Measured: 22-26 months corrected age
Secondary outcomes (3)
Number of Participants With a Serious Adverse Events (SAE)
Serious adverse events were prespecified. These included any symptomatic thrombosis involving a major vessel, unrelated to an infusion catheter requiring anticoagulation therapy, hematocrit level >65% or an increase of ≥15% in hematocrit in the absence of a preceding blood transfusion, hypertension (defined by receipt of antihypertensive therapy for more than 1 month, discharge with medication, or both), severe pulmonary hemorrhage, severe necrotizing enterocolitis (defined as Bell's stage 2b or 3), severe retinopathy of prematurity resulting in laser surgery or bevacizumab therapy, severe sepsis (defined as culture-proven bacterial or fungal sepsis resulting in blood-pressure support or substantive new respiratory support), grade 3 or 4 intracranial hemorrhage, cardiac arrest that did not result in death, and death.
Measured: From birth to hospital discharge (average 12-16 weeks depending on gestational age at birth)
Imaging
Brain MRI at 36 weeks PMA. Injury scoring was done using a modified scoring system of Kidokoro, with higher scores indicating greater brain injury. Scoring Range: 0-39
Measured: 36 weeks postmenstrual age
Biomarkers
Plasma Epo concentrations were measured in both groups within the first 24 h after birth before study drug administration (baseline), 30 minutes after study drug administration on day 7 (peak Epo concentration) and 30 minutes before study drug on day 9 (trough Epo) and a random level on day 14 after transition to subcutaneous dosing.
Measured: Baseline (first 24 hours after birth), days 7, 9 and 14 after birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2011 (estimated)
- Study startDec 2013
- Primary completion28 Feb 2019
- Study completion28 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Extreme PrematurityStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 941 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sandra E Juul, MD, PhD, University of Washington
- Investigators
- Sandra E Juul, MD, PhD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01378273
- Sponsor's protocol ID
- STUDY00007464
- Other IDs
- U01NS077953
- Acronym
- PENUT
- Status last verified
- Apr 2026
- First submitted
- 20 Jun 2011
- Last updated
- 19 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The Archived Clinical Research Datasets at NINDS are currently being migrated to new repositories, and data requests will no longer be accepted. If you require access to these datasets, please contact the Principal Investigators (PIs) of the respective studies.
Publications
Juul SE, Mayock DE, Comstock BA, Heagerty PJ. Neuroprotective potential of erythropoietin in neonates; design of a randomized trial. Matern Health Neonatol Perinatol. 2015 Dec 2;1:27. doi: 10.1186/s40748-015-0028-z. eCollection 2015.
PubMed 27057344Starr MC, Askenazi DJ, Goldstein SL, MacDonald JW, Bammler TK, Afsharinejad Z, D Brophy P, Juul SE, Mayock DE, Hingorani SR. Impact of processing methods on urinary biomarkers analysis in neonates. Pediatr Nephrol. 2018 Jan;33(1):181-186. doi: 10.1007/s00467-017-3779-0. Epub 2017 Aug 19.
PubMed 28821985Juul SE, Comstock BA, Wadhawan R, Mayock DE, Courtney SE, Robinson T, Ahmad KA, Bendel-Stenzel E, Baserga M, LaGamma EF, Downey LC, Rao R, Fahim N, Lampland A, Frantz ID III, Khan JY, Weiss M, Gilmore MM, Ohls RK, Srinivasan N, Perez JE, McKay V, Vu PT, Lowe J, Kuban K, O'Shea TM, Hartman AL, Heagerty PJ; PENUT Trial Consortium. A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants. N Engl J Med. 2020 Jan 16;382(3):233-243. doi: 10.1056/NEJMoa1907423.
PubMed 31940698Zhou MS, Griffin R, Askenazi DJ, Slagle CL, Chock VY, Menon S. Elevated serum creatinine over the first week of life and mortality risk in extremely preterm neonates: a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT). Pediatr Nephrol. 2026 Sep;41(9):3101-3110. doi: 10.1007/s00467-026-07294-7. Epub 2026 Apr 21.
PubMed 42012687Hanna M, Chock VY, Kamath N, Raj A, Swanson JR, Griffin R, Askenazi DJ, Nesargi S. Acute Kidney Injury and Neurodevelopmental Outcomes in Extremely Premature Neonates: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2025 Nov 3;8(11):e2543270. doi: 10.1001/jamanetworkopen.2025.43270.
PubMed 41222934Valentine GC, Brandon OC, Perez KM, Strobel KM, Mayock DE, Law JB, Neches S, German K, Kolnik S, Heagerty PJ, Wood TR, Juul SE. Time to regain birthweight and in-hospital outcomes among United States-born extremely preterm newborns. Pediatr Res. 2026 Feb;99(3):949-957. doi: 10.1038/s41390-025-04563-3. Epub 2025 Nov 10.
PubMed 41214292Zapata HA, Todurkar N, Favel K, Griffin RL, Starr MC, Charlton JR, McAdams RM, Askenazi D, Kulkarni T, Menon S, Mammen C, Harer MW. Association of delayed cord clamping with acute kidney injury and two-year kidney outcomes in extremely premature neonates: a secondary analysis of the preterm erythropoietin neuroprotection trial (PENUT). J Perinatol. 2025 Jan;45(1):85-93. doi: 10.1038/s41372-024-02143-7. Epub 2024 Oct 11.
PubMed 39390245Valentine GC, Perez KM, Wood TR, Mayock DE, Law JB, Kolnik S, Strobel KM, Brandon OC, Comstock BA, Heagerty PJ, Juul SE. Time to regain birthweight and association with neurodevelopmental outcomes among extremely preterm newborns. J Perinatol. 2024 Apr;44(4):554-560. doi: 10.1038/s41372-024-01869-8. Epub 2024 Jan 9.
PubMed 38195922Strobel KM, Wood TR, Valentine GC, German KR, Gogcu S, Hendrixson DT, Kolnik SE, Law JB, Mayock DE, Comstock BA, Heagerty PJ, Juul SE. Contemporary definitions of infant growth failure and neurodevelopmental and behavioral outcomes in extremely premature infants at two years of age. J Perinatol. 2024 Jun;44(6):811-818. doi: 10.1038/s41372-023-01852-9. Epub 2024 Jan 9.
PubMed 38195921Hingorani SR, Schmicker RH, Halloran B, Brophy P, Heagerty PJ, Juul S, Goldstein SL, Askenazi D; PENUT Investigators. Association Between Urinary Biomarkers and CKD in Extremely Low Gestational Age Neonates. Am J Kidney Dis. 2024 Apr;83(4):497-507. doi: 10.1053/j.ajkd.2023.09.008. Epub 2023 Nov 4.
PubMed 37926336Valentine G, Perez K, Wood T, Mayock D, Law J, Kolnik S, Strobel K, Brandon O, Comstock B, Heagerty P, Juul S. Time to Regain Birthweight and Association with Neurodevelopmental Outcomes among Extremely Preterm Newborns. Res Sq [Preprint]. 2023 Sep 14:rs.3.rs-3249598. doi: 10.21203/rs.3.rs-3249598/v1.
PubMed 37790304Starr MC, Griffin RL, Harer MW, Soranno DE, Gist KM, Segar JL, Menon S, Gordon L, Askenazi DJ, Selewski DT. Acute Kidney Injury Defined by Fluid-Corrected Creatinine in Premature Neonates: A Secondary Analysis of the PENUT Randomized Clinical Trial. JAMA Netw Open. 2023 Aug 1;6(8):e2328182. doi: 10.1001/jamanetworkopen.2023.28182.
PubMed 37561461Starr MC, Griffin R, Gist KM, Segar JL, Raina R, Guillet R, Nesargi S, Menon S, Anderson N, Askenazi DJ, Selewski DT; Neonatal Kidney Collaborative Research Committee. Association of Fluid Balance With Short- and Long-term Respiratory Outcomes in Extremely Premature Neonates: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2022 Dec 1;5(12):e2248826. doi: 10.1001/jamanetworkopen.2022.48826.
PubMed 36580332Hingorani S, Schmicker R, Ahmad KA, Frantz ID, Mayock DE, La Gamma EF, Baserga M, Khan JY, Gilmore MM, Robinson T, Brophy P, Heagerty PJ, Juul SE, Goldstein S, Askenazi D; PENUT Trial Consortium; PENUT Primary Investigators and coauthors. Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature. Clin J Am Soc Nephrol. 2022 Aug;17(8):1129-1138. doi: 10.2215/CJN.15011121. Epub 2022 Jul 19.
PubMed 35853728Garcia MR, Comstock BA, Patel RM, Tolia VN, Josephson CD, Georgieff MK, Rao R, Monsell SE, Juul SE, Ahmad KA; PENUT Trial Consortium. Iron supplementation and the risk of bronchopulmonary dysplasia in extremely low gestational age newborns. Pediatr Res. 2023 Feb;93(3):701-707. doi: 10.1038/s41390-022-02160-2. Epub 2022 Jun 20.
PubMed 35725917
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preterm Erythropoietin Neuroprotection Trial (PENUT Trial)
- ClinicalTrials.gov ID
- NCT01378273
- Acronym / sponsor ID
- PENUT / STUDY00007464
- Conditions
- Extreme Prematurity
- Keywords
- neuroprotection, erythropoietin, Epo, ELGANs, preterm, neonate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 941 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Dec 2013
- Primary completion
- 28 Feb 2019 (actual)
- Study completion
- 28 Feb 2020 (actual)
- First posted
- 22 Jun 2011 (estimated)
- Results
- Posted 17 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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).
- 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.
- To test whether Epo treatment decreases serial measures of circulating inflammatory mediators, and biomarkers of brain injury.
- 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.
Detailed 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.
Clinical information including co-morbidities of extreme prematurity, information about transfusions, and specific laboratory values were collected in the PENUT database.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Other: ControlSubjects will receive 6 doses of vehicle intravenously during the first 2 weeks of life. Doses will be administered at 48 hour intervals from the time of enrollment. Following high dose administration, sham subcutaneous injections will be given three times a week through to 32-6/7 weeks postmenstrual age. |
| Epo 1000 U/kg followed by 400 U/kg | Experimental | Drug: EpoSubjects will receive 6 doses of intravenous Epo 1000 U/kg/dose at 48 hour intervals from the time of enrollment. Following the high dose period, subjects will receive subcutaneous Epo 400 U/kg/dose three times a week until 32-6/7 weeks postmenstrual age. |
Who may qualify
- Ages
- 24 to 27 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- NICU inpatients between 24-0/7 and 27-6/7 weeks of gestation
- Less than twenty four hours of age
- Parental informed consent
Key exclusion criteria (4 listed)
- Major life-threatening anomalies (brain, cardiac, chromosomal anomalies)
- Hematologic crises such as DIC, or hemolysis due to blood group incompatibilities
- Polycythemia (hematocrit > 65)
- Congenital infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EpoAlso: Epotin, ErythropoietinEnrollment will occur within 24 hours of birth. Study drug will be administered intravenously for the first 6 doses. Subjects in the Epo arm will then receive 400 U/kg/dose three times a week until they reach 32-6/7 weeks postmenstrual age. Control infants will receive sham injections. | Drug | Epo 1000 U/kg followed by 400 U/kg |
| ControlAlso: SalineSubjects will receive 6 doses of vehicle intravenously during the first 2 weeks of life. Doses will be administered at 48 hour intervals from the time of enrollment. Following high dose administration, sham subcutaneous injections will be given three times a week through to 32-6/7 weeks postmenstrual age. | Other | Control |
Primary outcome
Number of Participants With Death or Severe Neurodevelopmental Impairment (NDI) at 22-26 Months Corrected Age
Time frame: 22-26 months corrected age
Severe NDI was defined as Bayley Scales of infant Development, 3rd edition composite motor score or composite cognitive score <70. This instrument is normed at 100 with standard deviation of 15. Cerebral palsy was classified as hemiplegia, diplegia, or quadriplegia, and severity was determined according to the Gross Motor Function Classification System (GMFCS) (levels range from 0 [no impairment] to 5 [most severe impairment]). Severe cerebral palsy was defined as a GMFCS level higher than 2.
3 secondary outcomes
Number of Participants With a Serious Adverse Events (SAE)
Time frame: From birth to hospital discharge (average 12-16 weeks depending on gestational age at birth)
Imaging
Time frame: 36 weeks postmenstrual age
Biomarkers
Time frame: Baseline (first 24 hours after birth), days 7, 9 and 14 after birth
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27057344Juul SE, Mayock DE, Comstock BA, Heagerty PJ. Neuroprotective potential of erythropoietin in neonates; design of a randomized trial. Matern Health Neonatol Perinatol. 2015 Dec 2;1:27. doi: 10.1186/s40748-015-0028-z. eCollection 2015.
- Results publication: PubMed 28821985Starr MC, Askenazi DJ, Goldstein SL, MacDonald JW, Bammler TK, Afsharinejad Z, D Brophy P, Juul SE, Mayock DE, Hingorani SR. Impact of processing methods on urinary biomarkers analysis in neonates. Pediatr Nephrol. 2018 Jan;33(1):181-186. doi: 10.1007/s00467-017-3779-0. Epub 2017 Aug 19.
- Results publication: PubMed 31940698Juul SE, Comstock BA, Wadhawan R, Mayock DE, Courtney SE, Robinson T, Ahmad KA, Bendel-Stenzel E, Baserga M, LaGamma EF, Downey LC, Rao R, Fahim N, Lampland A, Frantz ID III, Khan JY, Weiss M, Gilmore MM, Ohls RK, Srinivasan N, Perez JE, McKay V, Vu PT, Lowe J, Kuban K, O'Shea TM, Hartman AL, Heagerty PJ; PENUT Trial Consortium. A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants. N Engl J Med. 2020 Jan 16;382(3):233-243. doi: 10.1056/NEJMoa1907423.
- Derived from this study: PubMed 42012687Zhou MS, Griffin R, Askenazi DJ, Slagle CL, Chock VY, Menon S. Elevated serum creatinine over the first week of life and mortality risk in extremely preterm neonates: a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT). Pediatr Nephrol. 2026 Sep;41(9):3101-3110. doi: 10.1007/s00467-026-07294-7. Epub 2026 Apr 21.
- Derived from this study: PubMed 41222934Hanna M, Chock VY, Kamath N, Raj A, Swanson JR, Griffin R, Askenazi DJ, Nesargi S. Acute Kidney Injury and Neurodevelopmental Outcomes in Extremely Premature Neonates: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2025 Nov 3;8(11):e2543270. doi: 10.1001/jamanetworkopen.2025.43270.
- Derived from this study: PubMed 41214292Valentine GC, Brandon OC, Perez KM, Strobel KM, Mayock DE, Law JB, Neches S, German K, Kolnik S, Heagerty PJ, Wood TR, Juul SE. Time to regain birthweight and in-hospital outcomes among United States-born extremely preterm newborns. Pediatr Res. 2026 Feb;99(3):949-957. doi: 10.1038/s41390-025-04563-3. Epub 2025 Nov 10.
- Derived from this study: PubMed 39390245Zapata HA, Todurkar N, Favel K, Griffin RL, Starr MC, Charlton JR, McAdams RM, Askenazi D, Kulkarni T, Menon S, Mammen C, Harer MW. Association of delayed cord clamping with acute kidney injury and two-year kidney outcomes in extremely premature neonates: a secondary analysis of the preterm erythropoietin neuroprotection trial (PENUT). J Perinatol. 2025 Jan;45(1):85-93. doi: 10.1038/s41372-024-02143-7. Epub 2024 Oct 11.
- Derived from this study: PubMed 38195922Valentine GC, Perez KM, Wood TR, Mayock DE, Law JB, Kolnik S, Strobel KM, Brandon OC, Comstock BA, Heagerty PJ, Juul SE. Time to regain birthweight and association with neurodevelopmental outcomes among extremely preterm newborns. J Perinatol. 2024 Apr;44(4):554-560. doi: 10.1038/s41372-024-01869-8. Epub 2024 Jan 9.
- Derived from this study: PubMed 38195921Strobel KM, Wood TR, Valentine GC, German KR, Gogcu S, Hendrixson DT, Kolnik SE, Law JB, Mayock DE, Comstock BA, Heagerty PJ, Juul SE. Contemporary definitions of infant growth failure and neurodevelopmental and behavioral outcomes in extremely premature infants at two years of age. J Perinatol. 2024 Jun;44(6):811-818. doi: 10.1038/s41372-023-01852-9. Epub 2024 Jan 9.
- Derived from this study: PubMed 37926336Hingorani SR, Schmicker RH, Halloran B, Brophy P, Heagerty PJ, Juul S, Goldstein SL, Askenazi D; PENUT Investigators. Association Between Urinary Biomarkers and CKD in Extremely Low Gestational Age Neonates. Am J Kidney Dis. 2024 Apr;83(4):497-507. doi: 10.1053/j.ajkd.2023.09.008. Epub 2023 Nov 4.
- Derived from this study: PubMed 37790304Valentine G, Perez K, Wood T, Mayock D, Law J, Kolnik S, Strobel K, Brandon O, Comstock B, Heagerty P, Juul S. Time to Regain Birthweight and Association with Neurodevelopmental Outcomes among Extremely Preterm Newborns. Res Sq [Preprint]. 2023 Sep 14:rs.3.rs-3249598. doi: 10.21203/rs.3.rs-3249598/v1.
- Derived from this study: PubMed 37561461Starr MC, Griffin RL, Harer MW, Soranno DE, Gist KM, Segar JL, Menon S, Gordon L, Askenazi DJ, Selewski DT. Acute Kidney Injury Defined by Fluid-Corrected Creatinine in Premature Neonates: A Secondary Analysis of the PENUT Randomized Clinical Trial. JAMA Netw Open. 2023 Aug 1;6(8):e2328182. doi: 10.1001/jamanetworkopen.2023.28182.
- Individual participant dataSharing planned: Yes. The Archived Clinical Research Datasets at NINDS are currently being migrated to new repositories, and data requests will no longer be accepted. If you require access to these datasets, please contact the Principal Investigators (PIs) of the respective studies.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sandra E Juul, MD, PhD principal investigator
University of Washington
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Epo in people with Extreme Prematurity, run by University of Washington at 19 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Death or Severe Neurodevelopmental Impairment (NDI) at 22-26 Months Corrected Age (time frame: 22-26 months corrected age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01378273, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026.