Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00589953
Other study ID # R06-04-004
Secondary ID IND12537
Status Terminated
Phase Phase 2
First received December 27, 2007
Last updated July 29, 2013
Start date July 2007
Est. completion date September 2010

Study information

Verified date July 2013
Source Atlantic Health System
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Terminated
Enrollment 22
Est. completion date September 2010
Est. primary completion date September 2010
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group N/A to 24 Hours
Eligibility 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

Study Design


Intervention

Drug:
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.
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.

Locations

Country Name City State
United States Morristown Medical Center Morristown New Jersey

Sponsors (1)

Lead Sponsor Collaborator
Atlantic Health System

Country where clinical trial is conducted

United States, 

References & Publications (25)

Ascensao JL, Bilgrami S, Zanjani ED. Erythropoietin. Biology and clinical applications. Am J Pediatr Hematol Oncol. 1991 Winter;13(4):376-87. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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

Fisher JW. Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood). 2003 Jan;228(1):1-14. Review. — View Citation

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. — View Citation

Juul S. Recombinant erythropoietin as a neuroprotective treatment: in vitro and in vivo models. Clin Perinatol. 2004 Mar;31(1):129-42. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Maier RF, Obladen M, Müller-Hansen I, Kattner E, Merz U, Arlettaz R, Groneck P, Hammer H, Kössel 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Shalak L, Perlman JM. Hemorrhagic-ischemic cerebral injury in the preterm infant: current concepts. Clin Perinatol. 2002 Dec;29(4):745-63. Review. — View Citation

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. — View Citation

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. Epub 2005 Feb 17. — View Citation

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. Epub 2005 Apr 6. Review. — View Citation

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

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. — View Citation

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. — View Citation

* Note: There are 25 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Neurodevelopmental evaluations at 18 to 22 months corrected age (cerebral palsy, Bayley Scores of Infant Development Mental Development Index (MDI), Psychomotor Development Index (PDI), bilateral hearing aid use, and visual impairment) 18-22 months corrected age
Secondary Severe intraventricular hemorrhage First ten days of life
Secondary Polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, hemorrhage, seizure NICU hospitalization
See also
  Status Clinical Trial Phase
Completed NCT02710123 - Sub-Threshold Exercise Treatment for Adolescents With Sports Related Concussion N/A
Recruiting NCT02777060 - Exploring the Effectiveness of Sensor-based Balance Training on Patient Outcome Measures N/A
Completed NCT02262286 - MIND (Management of Traumatic Brain Injury Diagnosis) N/A
Completed NCT01461902 - Vasospasm in Pediatric Traumatic Brain Injury N/A
Recruiting NCT01198964 - Optimization of Human Cortical Stimulation
Active, not recruiting NCT01207050 - Effect of Rozerem on Sleep Among People With Traumatic Brain Injury Phase 4
Completed NCT01201863 - Neuroendocrine Dysfunction in Traumatic Brain Injury: Effects of Testosterone Therapy Phase 4
Completed NCT00875329 - Traumatic Brain Injury (TBI) Screening Instruments N/A
Completed NCT01059890 - Cerebral Antibiotics Distribution After Acute Brain Injury Phase 1
Completed NCT01035606 - Training in Goal-directed Attention Regulation for Individuals With Brain Injury N/A
Completed NCT00571623 - Automated Chest Physiotherapy to Improve Outcomes in Neuro N/A
Completed NCT00596765 - Neuropsychological Cognitive Behavioral Therapy for Patients With Acquired Brain Injury N/A
Completed NCT00336466 - The Erythropoietin NeuroProtective Effect: Assessment in CABG Surgery (TENPEAKS) Phase 2
Recruiting NCT05105763 - Biofeedback Gait Retraining for Stiff Knee Gait Correction N/A
Recruiting NCT02495558 - Cough Assessment in Patients With Severe Acquired Brain Injury N/A
Completed NCT02100592 - Early Verticalization in neuroICU With ERIGO: a Safety and Feasibility Study Phase 1/Phase 2
Completed NCT00797680 - Duration of Hypothermia for Neuroprotection After Pediatric Cardiac Arrest Phase 2
Completed NCT00018499 - Genotype Influence on Recovery After Traumatic Brain Injury N/A
Recruiting NCT02567201 - Electrophysiological Evaluation of Voluntary Attention N/A
Withdrawn NCT05581927 - Whole-Body Hypothermia for Neonates With Hypoxic-Ischemic Encephalopathy(HIE) N/A