High-Dose Erythropoietin in Extremely Premature Infants to Prevent/Attenuate Brain Injury: A Phase II Study

NCT ID: NCT00589953

Last Updated: 2013-07-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-07-31

Study Completion Date

2010-09-30

Brief Summary

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The highest risk for perinatal brain injury occurs among extremely premature infants who weigh less than 1250 grams at birth. Such perinatal brain injury is currently irreversible, associated with neurodevelopmental disability, and without adequate treatment modalities. Research in recent years suggest in both animal and human studies that erythropoietin (Epo) may have significant neuroprotective effects. Given the historical safe medical profile of Epo when used for anemia of prematurity but the likely need for a greater dosage regimen for activation of neuroprotective pathways against neonatal brain injury, we therefore propose this phase II study of high-dose Epo in very low birth weight infants for the prevention and/or attenuation of prematurity-related cerebral hemorrhagic-ischemic injury.

Detailed Description

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Eligible extremely premature infants will be enrolled in this double-blind, placebo-controlled randomized trial from the neonatal intensive care unit at Morristown Memorial Hospital (Morristown, New Jersey). Subjects will be enrolled within the first 24 hours of life and randomly assigned to receive Epo or saline vehicle placebo.

Standard NICU care will be provided to all subjects. Serial exams, CBC-d, reticulocyte counts, serum Epo levels, serial HUS, and head MRI will be collected at established time points during the study period. At 18 to 22 months corrected age, subjects will undergo a neurodevelopmental evaluation assessing for cerebral palsy, Bayley Scores of Infant Development-II (BSID-II) Mental Development Index (MDI), BSID-II Psychomotor Development Index (PDI), bilateral hearing aid use, and visual impairment.

Conditions

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Infant, Premature Erythropoietin Brain Injury Intraventricular Hemorrhage Periventricular Leukomalacia Neurodevelopmental Outcomes Randomized Clinical Trial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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EPO###

All subjects will be identified as a such by the study identifier "EPO###" where EPO designates enrollment in this study and ### is a numeric identifier (e.g. 103).

Group Type PLACEBO_COMPARATOR

Saline placebo

Intervention Type DRUG

Saline vehicle at a volume of 1 mL given over 1 hour intravenously once a day for the first seven days of life.

EPO ###

All subjects will be identified as a such by the study identifier "EPO###" where EPO designates enrollment in this study and ### is a numeric identifier (e.g. 103).

Group Type EXPERIMENTAL

Erythropoietin

Intervention Type DRUG

5 of first 10 subjects (Group 1): 400 units/kg/dose once daily for 7 days 5 of next 10 subjects (Group 2): 800 units/kg/dose once daily for 7 days 20 of next 30 subjects (Group 3): 1000 units/kg/dose once daily for 7 days administered i.v. over 1 hour.

The volume of the study drug will be 1 mL in a 1 mL Tuberculin syringe to be administered over 1 hour.

Interventions

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Erythropoietin

5 of first 10 subjects (Group 1): 400 units/kg/dose once daily for 7 days 5 of next 10 subjects (Group 2): 800 units/kg/dose once daily for 7 days 20 of next 30 subjects (Group 3): 1000 units/kg/dose once daily for 7 days administered i.v. over 1 hour.

The volume of the study drug will be 1 mL in a 1 mL Tuberculin syringe to be administered over 1 hour.

Intervention Type DRUG

Saline placebo

Saline vehicle at a volume of 1 mL given over 1 hour intravenously once a day for the first seven days of life.

Intervention Type DRUG

Other Intervention Names

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Confidential Randomization Number Confidential Randomization Number

Eligibility Criteria

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Inclusion Criteria

* 500 to 1250 grams at birth
* Less than 32 weeks gestation at birth
* Less than 24 hours of life at time of enrollment

Exclusion Criteria

* Congenital anomalies (chromosomal, CNS, cardiac, GI, pulmonary)
* Seizures within first 24 hours of life
* Severe neutropenia (ANC \< 500 cells/microL) within first 24 hours of life
* Polycythemia (Hct \> 65%) within first 24 hours of life
* Thrombocytopenia (platelets \< 50K cells/microL) within first 24 hours of life
* Hypertension (SBP \> 100mmHg) without vasopressor support within first 24 hours of life
Maximum Eligible Age

24 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Atlantic Health System

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Countries

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United States

References

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Lin FK, Suggs S, Lin CH, Browne JK, Smalling R, Egrie JC, Chen KK, Fox GM, Martin F, Stabinsky Z, et al. Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7580-4. doi: 10.1073/pnas.82.22.7580.

Reference Type BACKGROUND
PMID: 3865178 (View on PubMed)

Ascensao JL, Bilgrami S, Zanjani ED. Erythropoietin. Biology and clinical applications. Am J Pediatr Hematol Oncol. 1991 Winter;13(4):376-87. doi: 10.1097/00043426-199124000-00002.

Reference Type BACKGROUND
PMID: 1785666 (View on PubMed)

Buemi M, Aloisi C, Cavallaro E, Corica F, Floccari F, Grasso G, Lasco A, Pettinato G, Ruello A, Sturiale A, Frisina N. Recombinant human erythropoietin (rHuEPO): more than just the correction of uremic anemia. J Nephrol. 2002 Mar-Apr;15(2):97-103.

Reference Type BACKGROUND
PMID: 12018644 (View on PubMed)

Fisher JW. Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood). 2003 Jan;228(1):1-14. doi: 10.1177/153537020322800101.

Reference Type BACKGROUND
PMID: 12524467 (View on PubMed)

Maier RF, Obladen M, Muller-Hansen I, Kattner E, Merz U, Arlettaz R, Groneck P, Hammer H, Kossel H, Verellen G, Stock GJ, Lacaze-Masmonteil T, Claris O, Wagner M, Matis J, Gilberg F; European Multicenter Erythropoietin Beta Study Group. Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g. J Pediatr. 2002 Jul;141(1):8-15. doi: 10.1067/mpd.2002.124309.

Reference Type BACKGROUND
PMID: 12091844 (View on PubMed)

Ohls RK, Harcum J, Schibler KR, Christensen RD. The effect of erythropoietin on the transfusion requirements of preterm infants weighing 750 grams or less: a randomized, double-blind, placebo-controlled study. J Pediatr. 1997 Nov;131(5):661-5. doi: 10.1016/s0022-3476(97)70089-1.

Reference Type BACKGROUND
PMID: 9403642 (View on PubMed)

Shannon KM, Keith JF 3rd, Mentzer WC, Ehrenkranz RA, Brown MS, Widness JA, Gleason CA, Bifano EM, Millard DD, Davis CB, et al. Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants. Pediatrics. 1995 Jan;95(1):1-8.

Reference Type BACKGROUND
PMID: 7770284 (View on PubMed)

Meyer MP, Meyer JH, Commerford A, Hann FM, Sive AA, Moller G, Jacobs P, Malan AF. Recombinant human erythropoietin in the treatment of the anemia of prematurity: results of a double-blind, placebo-controlled study. Pediatrics. 1994 Jun;93(6 Pt 1):918-23.

Reference Type BACKGROUND
PMID: 8190577 (View on PubMed)

Ohls RK, Ehrenkranz RA, Wright LL, Lemons JA, Korones SB, Stoll BJ, Stark AR, Shankaran S, Donovan EF, Close NC, Das A. Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial. Pediatrics. 2001 Oct;108(4):934-42. doi: 10.1542/peds.108.4.934.

Reference Type BACKGROUND
PMID: 11581447 (View on PubMed)

Brown MS, Keith JF 3rd. Comparison between two and five doses a week of recombinant human erythropoietin for anemia of prematurity: a randomized trial. Pediatrics. 1999 Aug;104(2 Pt 1):210-5. doi: 10.1542/peds.104.2.210.

Reference Type BACKGROUND
PMID: 10428996 (View on PubMed)

Newton NR, Leonard CH, Piecuch RE, Phibbs RH. Neurodevelopmental outcome of prematurely born children treated with recombinant human erythropoietin in infancy. J Perinatol. 1999 Sep;19(6 Pt 1):403-6. doi: 10.1038/sj.jp.7200244.

Reference Type BACKGROUND
PMID: 10685268 (View on PubMed)

Maier RF, Obladen M, Kattner E, Natzschka J, Messer J, Regazzoni BM, Speer CP, Fellman V, Grauel EL, Groneck P, Wagner M, Moriette G, Salle BL, Verellen G, Scigalla P. High-versus low-dose erythropoietin in extremely low birth weight infants. The European Multicenter rhEPO Study Group. J Pediatr. 1998 May;132(5):866-70. doi: 10.1016/s0022-3476(98)70320-8.

Reference Type BACKGROUND
PMID: 9602202 (View on PubMed)

Shalak L, Perlman JM. Hemorrhagic-ischemic cerebral injury in the preterm infant: current concepts. Clin Perinatol. 2002 Dec;29(4):745-63. doi: 10.1016/s0095-5108(02)00048-9.

Reference Type BACKGROUND
PMID: 12516744 (View on PubMed)

Guzzetta F, Shackelford GD, Volpe S, Perlman JM, Volpe JJ. Periventricular intraparenchymal echodensities in the premature newborn: critical determinant of neurologic outcome. Pediatrics. 1986 Dec;78(6):995-1006.

Reference Type BACKGROUND
PMID: 3537951 (View on PubMed)

Bada HS, Green RS, Pourcyrous M, Leffler CW, Korones SB, Magill HL, Arheart K, Fitch CW, Anderson GD, Somes G, et al. Indomethacin reduces the risks of severe intraventricular hemorrhage. J Pediatr. 1989 Oct;115(4):631-7. doi: 10.1016/s0022-3476(89)80300-2.

Reference Type BACKGROUND
PMID: 2677294 (View on PubMed)

Schmidt B, Davis P, Moddemann D, Ohlsson A, Roberts RS, Saigal S, Solimano A, Vincer M, Wright LL; Trial of Indomethacin Prophylaxis in Preterms Investigators. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med. 2001 Jun 28;344(26):1966-72. doi: 10.1056/NEJM200106283442602.

Reference Type BACKGROUND
PMID: 11430325 (View on PubMed)

Juul S. Recombinant erythropoietin as a neuroprotective treatment: in vitro and in vivo models. Clin Perinatol. 2004 Mar;31(1):129-42. doi: 10.1016/j.clp.2004.03.004.

Reference Type BACKGROUND
PMID: 15183662 (View on PubMed)

Wen TC, Rogido M, Genetta T, Sola A. Permanent focal cerebral ischemia activates erythropoietin receptor in the neonatal rat brain. Neurosci Lett. 2004 Jan 30;355(3):165-8. doi: 10.1016/j.neulet.2003.10.078.

Reference Type BACKGROUND
PMID: 14732457 (View on PubMed)

Sola A, Rogido M, Lee BH, Genetta T, Wen TC. Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. Pediatr Res. 2005 Apr;57(4):481-7. doi: 10.1203/01.PDR.0000155760.88664.06. Epub 2005 Feb 17.

Reference Type BACKGROUND
PMID: 15718373 (View on PubMed)

Sola A, Wen TC, Hamrick SE, Ferriero DM. Potential for protection and repair following injury to the developing brain: a role for erythropoietin? Pediatr Res. 2005 May;57(5 Pt 2):110R-117R. doi: 10.1203/01.PDR.0000159571.50758.39. Epub 2005 Apr 6.

Reference Type BACKGROUND
PMID: 15817504 (View on PubMed)

Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F, Bohn M, Poser W, Ruther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Siren AL. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med. 2002 Aug;8(8):495-505.

Reference Type BACKGROUND
PMID: 12435860 (View on PubMed)

Juul SE, Harcum J, Li Y, Christensen RD. Erythropoietin is present in the cerebrospinal fluid of neonates. J Pediatr. 1997 Mar;130(3):428-30. doi: 10.1016/s0022-3476(97)70205-1.

Reference Type BACKGROUND
PMID: 9063419 (View on PubMed)

Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C, Itri LM, Cerami A. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10526-31. doi: 10.1073/pnas.97.19.10526.

Reference Type BACKGROUND
PMID: 10984541 (View on PubMed)

Widness JA, Veng-Pedersen P, Peters C, Pereira LM, Schmidt RL, Lowe LS. Erythropoietin pharmacokinetics in premature infants: developmental, nonlinearity, and treatment effects. J Appl Physiol (1985). 1996 Jan;80(1):140-8. doi: 10.1152/jappl.1996.80.1.140.

Reference Type BACKGROUND
PMID: 8847295 (View on PubMed)

Volpe JJ. Neurology of the newborn. 4th ed. Philadelphia: WB Saunders; 2001.

Reference Type BACKGROUND

Other Identifiers

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IND12537

Identifier Type: -

Identifier Source: secondary_id

R06-04-004

Identifier Type: -

Identifier Source: org_study_id

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