Trial Outcomes & Findings for High-dose Erythropoietin for Asphyxia and Encephalopathy (NCT NCT02811263)

Last Updated: 2023-01-30

Results Overview

Neurodevelopmental impairment defined as any of the following: a) Gross Motor Function Scale (GMFCS) level ≥ 1, or b) GMFCS = 0 or 0.5 and cerebral palsy (CP) (any type), or c) Bayley III Cognitive Score \< 90

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

500 participants

Primary outcome timeframe

Prior to final outcome assessment at 22-26 months of age; For extenuating circumstances, for example, COVID-19 restrictions, may be performed up to 36 months of age

Results posted on

2023-01-30

Participant Flow

Participant milestones

Participant milestones
Measure	Erythropoietin Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Overall Study STARTED	257	243
Overall Study COMPLETED	240	222
Overall Study NOT COMPLETED	17	21

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

High-dose Erythropoietin for Asphyxia and Encephalopathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erythropoietin n=257 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=243 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo	Total n=500 Participants Total of all reporting groups
Age, Continuous	29.6 years STANDARD_DEVIATION 6.3 • n=5 Participants	30.0 years STANDARD_DEVIATION 6.6 • n=7 Participants	29.6 years STANDARD_DEVIATION 6.3 • n=5 Participants
Sex: Female, Male Female	122 Participants n=5 Participants	103 Participants n=7 Participants	225 Participants n=5 Participants
Sex: Female, Male Male	135 Participants n=5 Participants	140 Participants n=7 Participants	275 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	63 Participants n=5 Participants	59 Participants n=7 Participants	122 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	194 Participants n=5 Participants	184 Participants n=7 Participants	378 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	18 Participants n=5 Participants	15 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	28 Participants n=5 Participants	38 Participants n=7 Participants	66 Participants n=5 Participants
Race (NIH/OMB) White	183 Participants n=5 Participants	173 Participants n=7 Participants	356 Participants n=5 Participants
Race (NIH/OMB) More than one race	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	18 Participants n=5 Participants	11 Participants n=7 Participants	29 Participants n=5 Participants
Region of Enrollment United States	257 participants n=5 Participants	243 participants n=7 Participants	500 participants n=5 Participants
Maternal education, high school or less	102 Participants n=5 Participants	83 Participants n=7 Participants	185 Participants n=5 Participants
Parity of 1, including trial infant	145 Participants n=5 Participants	141 Participants n=7 Participants	286 Participants n=5 Participants
Pregnancy and delivery complications - maternal chorioamnionitis or fever	45 Participants n=5 Participants	32 Participants n=7 Participants	77 Participants n=5 Participants
Pregnancy and delivery complications - maternal preeclampsia or eclampsia	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Pregnancy and delivery complications - gestational diabetes	33 Participants n=5 Participants	25 Participants n=7 Participants	58 Participants n=5 Participants
Pregnancy and delivery complications - maternal obesity: body-mass index >30	47 Participants n=5 Participants	42 Participants n=7 Participants	89 Participants n=5 Participants
Pregnancy and delivery complications - sentinel event	71 Participants n=5 Participants	72 Participants n=7 Participants	143 Participants n=5 Participants
Pregnancy and delivery complications - sentinel event (shoulder dystocia)	14 Participants n=5 Participants	18 Participants n=7 Participants	32 Participants n=5 Participants
Pregnancy and delivery complications - sentinel event (placental abruption)	40 Participants n=5 Participants	31 Participants n=7 Participants	71 Participants n=5 Participants
Pregnancy and delivery complications - sentinel event (prolapsed cord)	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Pregnancy and delivery complications - sentinel event (uterine rupture)	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Pregnancy and delivery complications - Cesarean section delivery	170 Participants n=5 Participants	159 Participants n=7 Participants	329 Participants n=5 Participants
Pregnancy and delivery complications - outborn delivery	214 Participants n=5 Participants	201 Participants n=7 Participants	415 Participants n=5 Participants
Infant birth weight	3332 grams STANDARD_DEVIATION 572 • n=5 Participants	3414 grams STANDARD_DEVIATION 614 • n=7 Participants	3372 grams STANDARD_DEVIATION 594 • n=5 Participants
Infant gestational age	39.1 weeks STANDARD_DEVIATION 1.4 • n=5 Participants	39.2 weeks STANDARD_DEVIATION 1.5 • n=7 Participants	39.1 weeks STANDARD_DEVIATION 1.5 • n=5 Participants
Infant 5-minute Apgar score	3 score on a scale n=5 Participants	3 score on a scale n=7 Participants	3 score on a scale n=5 Participants
Infant 10-minute Apgar score	5 score on a scale n=5 Participants	5 score on a scale n=7 Participants	5 score on a scale n=5 Participants
Infant - continued resuscitation at 10 minutes	243 Participants n=5 Participants	217 Participants n=7 Participants	460 Participants n=5 Participants
Infant - lowest pH	6.95 pH STANDARD_DEVIATION 0.17 • n=5 Participants	6.91 pH STANDARD_DEVIATION 0.17 • n=7 Participants	6.93 pH STANDARD_DEVIATION 0.17 • n=5 Participants
Infant - severe encephalopathy	59 Participants n=5 Participants	54 Participants n=7 Participants	113 Participants n=5 Participants
Infant - age at randomization	14 hours n=5 Participants	14 hours n=7 Participants	14 hours n=5 Participants
Infant - age at first treatment	17.6 hours STANDARD_DEVIATION 5.5 • n=5 Participants	17.6 hours STANDARD_DEVIATION 5.5 • n=7 Participants	17.6 hours STANDARD_DEVIATION 5.5 • n=5 Participants

PRIMARY outcome

Timeframe: Prior to final outcome assessment at 22-26 months of age; For extenuating circumstances, for example, COVID-19 restrictions, may be performed up to 36 months of age

Outcome measures

Outcome measures
Measure	Erythropoietin n=240 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=222 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Number of Participants With Death or Neurodevelopmental Impairment	126 Participants	110 Participants

SECONDARY outcome

Timeframe: 22-26 months; For extenuating circumstances, for example, COVID-19 restrictions, may be performed up to 36 months of age

Population: All toddlers evaluated with a neuro exam at 22-26 months

Neurologic diagnoses: no CP, diparetic CP, hemiparetic CP, quadriparetic CP

Outcome measures

Outcome measures
Measure	Erythropoietin n=207 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=198 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Number of Participants With Cerebral Palsy (CP) and Number of Participants With Each Type of Cerebral Palsy (CP), Determined Using a Standardized Neurologic Examination No cerebral palsy	176 Participants	173 Participants
Number of Participants With Cerebral Palsy (CP) and Number of Participants With Each Type of Cerebral Palsy (CP), Determined Using a Standardized Neurologic Examination Diparetic cerebral palsy	9 Participants	6 Participants
Number of Participants With Cerebral Palsy (CP) and Number of Participants With Each Type of Cerebral Palsy (CP), Determined Using a Standardized Neurologic Examination Hemiparetic cerebral palsy	3 Participants	2 Participants
Number of Participants With Cerebral Palsy (CP) and Number of Participants With Each Type of Cerebral Palsy (CP), Determined Using a Standardized Neurologic Examination Quadriparetic cerebral palsy	19 Participants	17 Participants

SECONDARY outcome

Timeframe: 22-26 months; For extenuating circumstances, for example, COVID-19 restrictions, may be performed up to 36 months of age

Population: The analysis population includes participants with GMFCS score available. Total number of participants analyzed in the Participant Flow module (N=240, N=222) is higher, as it reflects participants for whom the primary endpoint of death or neurodevelopmental impairment (NDI) could be determined. The primary endpoint can be determined when thresholds are met on either neurologic examination, Bayley III cognitive score, or GMFCS score, or when death occurred.

Gross Motor Function Scale (GMFCS) is a scale from 0-5, with higher values representing worse outcomes. * Level 0: Walks 10 steps independently with symmetrical gait * Level 0.5: Walks 10 steps independently without symmetrical gait * Level 1: Sits. Hands free for play, and creeps or crawls on hands and knees, pulls to stand; cruises or walks with hands held * Level 2: Uses hands for sitting support; creeps on stomach or crawls, may cruise/pull to stand * Level 3: Sits with external support for lower trunk; rolls, creeps on stomach * Level 4: Good head control in supported sitting; can roll to supine, may roll to prone * Level 5: Unable to maintain anti-gravity head and trunk postures in prone or sitting; little or no voluntary movement.

Outcome measures

Outcome measures
Measure	Erythropoietin n=211 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=204 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Number of Participants With Each Level of Gross Motor Function, Determined Using the GMFCS GMFCS = 0	186 Participants	178 Participants
Number of Participants With Each Level of Gross Motor Function, Determined Using the GMFCS GMFCS = 0.5	6 Participants	6 Participants
Number of Participants With Each Level of Gross Motor Function, Determined Using the GMFCS GMFCS = 1	4 Participants	6 Participants
Number of Participants With Each Level of Gross Motor Function, Determined Using the GMFCS GMFCS = 2	3 Participants	5 Participants
Number of Participants With Each Level of Gross Motor Function, Determined Using the GMFCS GMFCS = 3	2 Participants	1 Participants
Number of Participants With Each Level of Gross Motor Function, Determined Using the GMFCS GMFCS = 4	4 Participants	1 Participants
Number of Participants With Each Level of Gross Motor Function, Determined Using the GMFCS GMFCS = 5	6 Participants	7 Participants

SECONDARY outcome

Timeframe: 22-26 months; For extenuating circumstances, for example, COVID-19 restrictions, may be performed up to 36 months of age

Population: The analysis population includes participants with Bayley III cognitive score available. Total number of participants analyzed in the Participant Flow module (N=240, N=222) is higher, as it reflects participants for whom the primary endpoint of death or neurodevelopmental impairment (NDI) could be determined. The primary endpoint can be determined when thresholds are met on either neurologic examination, Bayley III cognitive score, or GMFCS score, or when death occurred.

The Bayley III cognitive score is a population normed score. 100 indicates the population mean with a standard deviation of 15; higher scores indicate a higher level of development.

Outcome measures

Outcome measures
Measure	Erythropoietin n=200 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=192 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Bayley III Cognitive Score	89.1 score on a scale Standard Deviation 15.7	89.5 score on a scale Standard Deviation 17.5

SECONDARY outcome

Timeframe: 22-26 months; For extenuating circumstances, for example, COVID-19 restrictions, may be performed up to 36 months of age

Population: The analysis population includes participants with Bayley III language score available. Total number of participants analyzed in the Participant Flow module (N=240, N=222) is higher, as it reflects participants for whom the primary endpoint of death or neurodevelopmental impairment (NDI) could be determined. The primary endpoint can be determined when thresholds are met on either neurologic examination, Bayley III cognitive score, or GMFCS score, or when death occurred.

The Bayley III language score is a population normed score. 100 indicates the population mean with a standard deviation of 15; higher scores indicate a higher level of development.

Outcome measures

Outcome measures
Measure	Erythropoietin n=198 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=188 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Bayley III Language Score	87.9 score on a scale Standard Deviation 20.4	86.7 score on a scale Standard Deviation 20.8

SECONDARY outcome

Timeframe: Prior to 22-26 months

Population: The analysis population includes participants with data regarding epilepsy available. Total number of participants analyzed in the Participant Flow module (N=240, N=222) is higher, as it reflects participants for whom the primary endpoint of death or neurodevelopmental impairment (NDI) could be determined. The primary endpoint can be determined when thresholds are met on either neurologic examination, Bayley III cognitive score, or GMFCS score, or when death occurred.

≥ 2 afebrile, unprovoked seizures

Outcome measures

Outcome measures
Measure	Erythropoietin n=210 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=205 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Number of Participants With Epilepsy	5 Participants	4 Participants

SECONDARY outcome

Timeframe: 22-26 months

Population: The analysis population includes participants with Child Behavior Checklist scores available. Total number of participants analyzed in the Participant Flow module (N=240, N=222) is higher, as it reflects participants for whom the primary endpoint of death or neurodevelopmental impairment (NDI) could be determined. The primary endpoint can be determined when thresholds are met on either neurologic examination, Bayley III cognitive score, or GMFCS score, or when death occurred.

Score for externalizing problems on Childhood Behavior Checklist of \>= 65

Outcome measures

Outcome measures
Measure	Erythropoietin n=207 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=201 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Number of Participants With Behavioral Abnormalities Determined by the Externalizing Score of the Child Behavior Checklist	15 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Through 22-26 months

Mild impairment: GMFCS=1 and no cerebral palsy, or GMFCS\<=0.5 and hemiplegic or diplegic cerebral palsy. Moderate/severe impairment: GMFCS=1 and cerebral palsy, GMFCS \>=2, quadriplegic cerebral palsy, or Bayley III cognitive score \<85.

Outcome measures

Outcome measures
Measure	Erythropoietin n=240 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=222 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Number of Participants at Each Level of Severity of Impairment [(1) Normal, (2) Mild Motor and/or Cognitive Impairment, (3) Moderate/Severe Motor and or Cognitive Impairment, (4) Death], Compared Between the Epo and Placebo Groups. Mild motor and/or cognitive impairment	26 Participants	23 Participants
Number of Participants at Each Level of Severity of Impairment [(1) Normal, (2) Mild Motor and/or Cognitive Impairment, (3) Moderate/Severe Motor and or Cognitive Impairment, (4) Death], Compared Between the Epo and Placebo Groups. Normal	114 Participants	112 Participants
Number of Participants at Each Level of Severity of Impairment [(1) Normal, (2) Mild Motor and/or Cognitive Impairment, (3) Moderate/Severe Motor and or Cognitive Impairment, (4) Death], Compared Between the Epo and Placebo Groups. Moderate/severe impairment	63 Participants	59 Participants
Number of Participants at Each Level of Severity of Impairment [(1) Normal, (2) Mild Motor and/or Cognitive Impairment, (3) Moderate/Severe Motor and or Cognitive Impairment, (4) Death], Compared Between the Epo and Placebo Groups. Death	37 Participants	28 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Through hospital discharge

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Through 22-26 months

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: During first week of life

Population: The analysis population includes participants with biologic samples available. Total number of participants analyzed in the Participant Flow module (N=240, N=222) differs, as it reflects participants for whom the primary endpoint of death or neurodevelopmental impairment (NDI) could be determined. The primary endpoint can be determined when thresholds are met on either neurologic examination, Bayley III cognitive score, or GMFCS score, or when death occurred.

Epo level at baseline, day 2, and day 4.

Outcome measures

Outcome measures
Measure	Erythropoietin n=228 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=217 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Serial Circulating Biomarkers of Inflammation/Brain Injury Baseline	32.7 mU/ml Interval 13.5 to 183.4	36.0 mU/ml Interval 12.3 to 96.7
Serial Circulating Biomarkers of Inflammation/Brain Injury Day 2	1530 mU/ml Interval 1259.0 to 5802.0	34.4 mU/ml Interval 18.0 to 91.9
Serial Circulating Biomarkers of Inflammation/Brain Injury Day 4	2682 mU/ml Interval 2190.0 to 4637.0	20.5 mU/ml Interval 8.1 to 54.7

OTHER_PRE_SPECIFIED outcome

Timeframe: During first week of life

Population: The analysis population includes participants with brain MRI data from the first week of life available. Total number of participants analyzed in the Participant Flow module (N=240, N=222) differs, as it reflects participants for whom the primary endpoint of death or neurodevelopmental impairment (NDI) could be determined. The primary endpoint can be determined when thresholds are met on either neurologic examination, Bayley III cognitive score, or GMFCS score, or when death occurred.

Global brain injury scores were calculated using a validated scoring system for HIE. The extent of injury was recorded (i.e., none = 0, \<25% = 1, 25-50% = 2; \>50% = 3) as seen on T1, T2, and apparent diffusion coefficient (ADC) images in 8 regions of the brain: caudate, putamen/globus pallidus, thalamus, posterior limb of t he internal capsule (PLIC), cortex, white matter, brainstem, and cerebellum. The severity of brain injury was determined from the global injury score as follows: none (global injury score = 0), mild (1-11), moderate (12-32), or severe (33-138).

Outcome measures

Outcome measures
Measure	Erythropoietin n=242 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=231 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
MR Evidence of Brain Injury - Brain Injury Score	8 score on a scale Interval 2.0 to 26.0	7 score on a scale Interval 2.0 to 20.0

OTHER_PRE_SPECIFIED outcome

Timeframe: During first week of life

Outcome measures

Outcome measures
Measure	Erythropoietin n=242 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=231 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Number of Participants With MR Evidence of Brain Injury - Severity of Brain Injury None	49 Participants	51 Participants
Number of Participants With MR Evidence of Brain Injury - Severity of Brain Injury Mild	91 Participants	86 Participants
Number of Participants With MR Evidence of Brain Injury - Severity of Brain Injury Moderate	46 Participants	51 Participants
Number of Participants With MR Evidence of Brain Injury - Severity of Brain Injury Severe	56 Participants	43 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Through 22-26 months

Population: The analysis population includes participants with hearing impairment data available. Total number of participants analyzed in the Participant Flow module (N=240, N=222) differs, as it reflects participants for whom the primary endpoint of death or neurodevelopmental impairment (NDI) could be determined. The primary endpoint can be determined when thresholds are met on either neurologic examination, Bayley III cognitive score, or GMFCS score, or when death occurred.

Outcome measures

Outcome measures
Measure	Erythropoietin n=211 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=203 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Number of Participants Experiencing Hearing Impairment Requiring Hearing Aids, Per Parent/Caregiver Report, Compared Between the Epo and Placebo Groups.	10 Participants	13 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Through 22-26 months

Population: The analysis population includes participants with visual impairment data available. Total number of participants analyzed in the Participant Flow module (N=240, N=222) differs, as it reflects participants for whom the primary endpoint of death or neurodevelopmental impairment (NDI) could be determined. The primary endpoint can be determined when thresholds are met on either neurologic examination, Bayley III cognitive score, or GMFCS score, or when death occurred.

Outcome measures

Outcome measures
Measure	Erythropoietin n=211 Participants Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=203 Participants Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
Number of Participants Experiencing Cortical Visual Impairment, Per Parent/Caregiver Report, Compared Between the Epo and Placebo Groups.	19 Participants	20 Participants

Adverse Events

Erythropoietin

Serious events: 137 serious events

Other events: 254 other events

Deaths: 37 deaths

Placebo

Serious events: 106 serious events

Other events: 240 other events

Deaths: 28 deaths

Serious adverse events

Serious adverse events
Measure	Erythropoietin n=257 participants at risk Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses) Erythropoietin: Epogen drawn from commercially available single dose 4000U/mL vials	Placebo n=243 participants at risk Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age Normal saline placebo: Equal volume of normal saline to be used as placebo
General disorders Death	14.4% 37/257 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.	11.5% 28/243 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.
Cardiac disorders Systemic hypertension	2.7% 7/257 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.	2.9% 7/243 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.
Blood and lymphatic system disorders Polycythemia	0.00% 0/257 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.	0.00% 0/243 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.
Blood and lymphatic system disorders Major venous or arterial thrombosis	2.3% 6/257 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.	1.2% 3/243 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.
Blood and lymphatic system disorders Disseminated intravascular coagulation	15.2% 39/257 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.	10.3% 25/243 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.
Cardiac disorders Pulmonary hypertension	19.8% 51/257 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.	14.8% 36/243 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.
Blood and lymphatic system disorders Intracranial hemorrhage	26.5% 68/257 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.	22.6% 55/243 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.
Cardiac disorders Cardiopulmonary arrest	1.2% 3/257 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.	1.2% 3/243 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.
General disorders Other unexpected life threatening event	3.9% 10/257 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.	2.5% 6/243 • Adverse Events were collected through hospital discharge from birth, regardless of duration of hospitalization (mean = 21.4 days; median = 14 days; range = 5-187 days). Serious Adverse Events were collected through 30 days of study drug dosing. Death occurring at any time during the neonatal or follow-up period (up to 36 months) was also reported as a Serious Adverse Event. Adverse Events: anticipated medical complications of hypoxic-ischemic encephalopathy. Serious Adverse Events: systemic hypertension, polycythemia, disseminated intravascular coagulation, major venous or arterial thrombosis (clot), pulmonary hypertension, intracranial hemorrhage, cardiopulmonary arrest, other unexpected life-threatening event, death.

Other adverse events

Additional Information

Yvonne W. Wu, MD, MPH

University of California, San Francisco

Phone: (415) 353-2400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place