Infant, PrematurePhase 2NCT00589953

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

A Phase 2 study testing Erythropoietin in people with Infant, Premature and Erythropoietin, run by Atlantic Health System at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages Up to 24 hoursHealthy volunteers can take part
Conditions the study is for: Infant, Premature, Erythropoietin, Brain Injury
What is being tested?: Erythropoietin
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 22 participants
Where: 1 siteUnited States
Study dates: Jul 2007to Sep 2010
Phase: Phase 2
Are there results?: None posted in the registry

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 Up to 24 hours
All sexes
Healthy volunteers accepted
Child

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Morristown Medical Center
Morristown, New Jersey, 07960

Other trials in United States

About this study

Official title: High-Dose Erythropoietin in Very Low Birth Weight Infants for the Potential Treatment of Prematurity-Related Cerebral Hemorrhagic-Ischemic Injury: A Phase II Safety/Tolerability Study

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.

Read the detailed 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.

Conditions: Infant, Premature, Erythropoietin, Brain Injury, Intraventricular Hemorrhage, Periventricular Leukomalacia, Neurodevelopmental Outcomes
Being tested: Erythropoietin, Saline placebo
Keywords: Extreme Prematurity, Erythropoietin, Perinatal Brain Injury, Intraventricular Hemorrhage, Periventricular Leukomalacia, Neurodevelopmental Outcomes, Randomized Clinical Trial
Medical subject headings: Premature Birth, Brain Injuries, Leukomalacia, Periventricular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ErythropoietinDrug
Also called Confidential Randomization Number
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 placeboDrug
Also called Confidential Randomization Number
Saline vehicle at a volume of 1 mL given over 1 hour intravenously once a day for the first seven days of life.

Study groups in NCT00589953
Study group	Role	What they receive
EPO###	Placebo comparator	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). Receives: Drug: Saline placebo
EPO ###	Experimental	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). Receives: Drug: Erythropoietin

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 18-22 months corrected age

Secondary outcomes (2)

Severe intraventricular hemorrhage
Measured: First ten days of life
Polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, hemorrhage, seizure
Measured: NICU hospitalization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2007Sep 2010

First posted10 Jan 2008 (estimated)
Study startJul 2007
Primary completionSep 2010
Study completionSep 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (25)Papers the sponsor has linked to this study.
Other trials for Infant, PrematureStudies of the same condition, open and under way.
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 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00589953
Sponsor's protocol ID: R06-04-004
Other IDs: IND12537
Status last verified: Jul 2013
First submitted: 27 Dec 2007
Last updated: 30 Jul 2013
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 3865178
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.
PubMed 1785666
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.
PubMed 12018644
Fisher JW. Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood). 2003 Jan;228(1):1-14. doi: 10.1177/153537020322800101.
PubMed 12524467
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.
PubMed 12091844
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.
PubMed 9403642
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.
PubMed 7770284
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.
PubMed 8190577
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.
PubMed 11581447
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.
PubMed 10428996
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.
PubMed 10685268
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.
PubMed 9602202
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.
PubMed 12516744
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.
PubMed 3537951
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.
PubMed 2677294

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Infant, Premature trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: High-Dose Erythropoietin in Very Low Birth Weight Infants for the Potential Treatment of Prematurity-Related Cerebral Hemorrhagic-Ischemic Injury: A Phase II Safety/Tolerability Study
ClinicalTrials.gov ID: NCT00589953
Acronym / sponsor ID: R06-04-004
Conditions: Infant, Premature, Erythropoietin, Brain Injury, Intraventricular Hemorrhage, Periventricular Leukomalacia, Neurodevelopmental Outcomes
Keywords: Extreme Prematurity, Erythropoietin, Perinatal Brain Injury, Intraventricular Hemorrhage, Periventricular Leukomalacia, Neurodevelopmental Outcomes, Randomized Clinical Trial
Phase: Phase 2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 22 participants (actual)
Lead sponsor: Atlantic Health SystemUniversity, hospital or other
Study start: Jul 2007
Primary completion: Sep 2010 (actual)
Study completion: Sep 2010 (actual)
First posted: 10 Jan 2008 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
EPO###	Placebo comparator	Drug: Saline placeboAll 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).
EPO ###	Experimental	Drug: ErythropoietinAll 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).

Who may qualify

Ages: Up to 24 hours
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (3 listed)

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

Key exclusion criteria (6 listed)

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

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
ErythropoietinAlso: Confidential Randomization Number5 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.	Drug	EPO ###
Saline placeboAlso: Confidential Randomization NumberSaline vehicle at a volume of 1 mL given over 1 hour intravenously once a day for the first seven days of life.	Drug	EPO###

Primary outcome

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)
Time frame: 18-22 months corrected age

2 secondary outcomes

Severe intraventricular hemorrhage
Time frame: First ten days of life
Polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, hemorrhage, seizure
Time frame: NICU hospitalization

Results and safety

The study was stopped early. Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2013.
Background: PubMed 3865178Lin 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.
Background: PubMed 1785666Ascensao 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.
Background: PubMed 12018644Buemi 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.
Background: PubMed 12524467Fisher JW. Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood). 2003 Jan;228(1):1-14. doi: 10.1177/153537020322800101.
Background: PubMed 12091844Maier 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.
Background: PubMed 9403642Ohls 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.
Background: PubMed 7770284Shannon 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.
Background: PubMed 8190577Meyer 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.
Background: PubMed 11581447Ohls 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.
Background: PubMed 10428996Brown 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.
Background: PubMed 10685268Newton 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.
Background: PubMed 9602202Maier 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.

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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.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Erythropoietin in people with Infant, Premature and Erythropoietin, run by Atlantic Health System at 1 site 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 6 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: stopped early, as of the sponsor's last update on 30 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

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?

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) (time frame: 18-22 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 NCT00589953, which also lists 25 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 30 Jul 2013.