A Phase 3 interventional study of Normal saline placebo and Erythropoietin in Neonatal Encephalopathy and Birth Asphyxia, sponsored by University of California, San Francisco. Completed at 23 sites in United States. Open to participants aged Up to 24 Hours. Per ClinicalTrials.gov, last updated 2023-01-30.
Sponsored by University of California, San Francisco · Phase 3, Interventional, and Treatment
Among 15 studies in Asphyxia Neonatorum with a site in United States — 2 open to participants now, 3 under way, 1 of them phase 3. Asphyxia Neonatorum · United States.
Among the 15 studies in Asphyxia Neonatorum with a site in United States, this one is the 2nd largest by enrollment of the 11 interventional ones that give a count, is the only one that started in 2017, is the only one in phase 3, and was the 6th registered.
106 studies on the registry are indexed under Asphyxia Neonatorum; 19 are open to participants now.
Browse Asphyxia Neonatorum studies →2 of the 15 studies in Asphyxia Neonatorum with a site in United States are open now. Recruiting first, the newest first:
Pia Wintermark · Sites in United States, Canada
Ages 0 min–48 hrs
ReAlta Life Sciences, Inc. · Sites in United States
Ages up to 10 hrs
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 15 Asphyxia Neonatorum studies recruiting now, 3 (20%) set no upper age limit and 12 (80%) stop at 75 or younger; 15 take children under 18; 2 take healthy volunteers.
This study: Up to 24 Hours · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
15 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 2 · Phase 2 3 · Phase 3 2
First in 1999; this study’s year is marked. 1 started in 2017.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 500 is above the median of 173 across 73 interventional studies indexed under Asphyxia Neonatorum.
Median enrollment 173 across the 11 interventional studies, 61 across the 4 observational. Of the 12 that completed or were terminated, 5 (42%) have results posted.
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3 of 15 have an industry lead sponsor. The 10 most frequent:
University of California, San Francisco is the lead sponsor of 2,170 studies on the registry; 370 are open to participants now.
Of its 268 completed or terminated interventional studies of FDA-regulated products, 203 (76%) have results posted.
University of California, San Francisco has 3 studies filed under Asphyxia Neonatorum — fewer than ten, so there is no comparison to draw.
1 of the studies in Asphyxia Neonatorum with a site in United States that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT05778188Phase 3ReAlta Life Sciences, Inc.A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia | 2026-12 |
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Among the 15 studies in Asphyxia Neonatorum with a site in United States, from their registry updates:
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Hypoxic-ischemic encephalopathy (HIE) occurs when a baby gets reduced blood flow and oxygen to the brain near the time of birth. This results in death or neurologic disabilities including cerebral palsy and cognitive impairment in up to half of affected infants. This clinical trial will determine if the drug erythropoietin (Epo) added to hypothermia (usual therapy) will improve outcomes for infants suffering from HIE.
Neonatal hypoxic-ischemic encephalopathy (HIE) refers to brain injury resulting from reduced blood and oxygen flow to a baby's brain near the time of birth. HIE affects up to 12,000 newborns each year in the U.S. Half of affected infants have a bad outcome including death, cerebral palsy and cognitive impairment despite receiving hypothermia, the only available treatment. Erythropoietin (Epo) is a cytokine with remarkable neuroprotective and neuroregenerative effects demonstrated in animal models of neonatal brain injury. In a phase I trial of Epo + hypothermia, the investigators found that Epo 1000 U/Kg/dose best reproduced the pharmacokinetics of neuroprotective dosing in animal models. Long term outcomes were better than expected based on entry criteria and MRI findings. A phase II trial compared 50 cooled infants randomized to receive Epo or placebo. Infants treated with hypothermia + Epo had less brain injury on early MRI, and better 12-month motor development. The investigators hypothesize that Epo given to cooled infants with moderate/severe HIE will reduce the combined primary outcome of death or neurodevelopmental impairment from 49 to 33%. This is a randomized, double-blind, placebo-controlled trial of Epo therapy in 500 infants with HIE undergoing hypothermia. Specific aims are 1) To determine if 5 doses of Epo 1000 U/kg IV reduces the rate of death, motor or cognitive deficits at 2 years; 2) To assess safety of Epo by evaluating clinical toxicity; and 3) To determine whether Epo decreases the severity of neonatal brain injury as evidenced by early MRI and circulating biomarkers of brain injury. The investigators anticipate that Epo will confer improved 2-year neurodevelopmental outcome, will be safe, and will decrease brain injury severity as determined by early biomarkers.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Perinatal depression based on at least one of the following:
Exclusion Criteria:
Erythropoietin 1000 U/kg IV, at about 1, 2, 3, 4, and 7 days of age (i.e., 5 doses)
Drug: Erythropoietin
Normal saline IV (equal volume), at about 1, 2, 3, 4, and 7 days of age
Drug: Normal saline placebo
Equal volume of normal saline to be used as placebo
Also known as: NS
Epogen drawn from commercially available single dose 4000U/mL vials
Also known as: Epogen
Number of Participants With Death or Neurodevelopmental Impairment
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
Time frame: 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
Number of Participants With Cerebral Palsy (CP) and Number of Participants With Each Type of Cerebral Palsy (CP), Determined Using a Standardized Neurologic Examination
Neurologic diagnoses: no CP, diparetic CP, hemiparetic CP, quadriparetic CP
Time frame: 22-26 months; For extenuating circumstances, for example, COVID-19 restrictions, may be performed up to 36 months of age
Number of Participants With Each Level of Gross Motor Function, Determined Using the GMFCS
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.
Time frame: 22-26 months; For extenuating circumstances, for example, COVID-19 restrictions, may be performed up to 36 months of age
Bayley III Cognitive Score
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.
Time frame: 22-26 months; For extenuating circumstances, for example, COVID-19 restrictions, may be performed up to 36 months of age
Bayley III Language Score
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.
Time frame: 22-26 months; For extenuating circumstances, for example, COVID-19 restrictions, may be performed up to 36 months of age
Number of Participants With Epilepsy
≥ 2 afebrile, unprovoked seizures
Time frame: Prior to 22-26 months
Number of Participants With Behavioral Abnormalities Determined by the Externalizing Score of the Child Behavior Checklist
Score for externalizing problems on Childhood Behavior Checklist of \>= 65
Time frame: 22-26 months
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 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.
Time frame: Through 22-26 months
Rates of Epo-related Adverse Events
Time frame: Through hospital discharge
Rates of Epo-related Adverse Events
Time frame: Through 22-26 months
Serial Circulating Biomarkers of Inflammation/Brain Injury
Epo level at baseline, day 2, and day 4.
Time frame: During first week of life
MR Evidence of Brain Injury - Brain Injury Score
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).
Time frame: During first week of life
Number of Participants With MR Evidence of Brain Injury - Severity of Brain Injury
Time frame: During first week of life
Number of Participants Experiencing Hearing Impairment Requiring Hearing Aids, Per Parent/Caregiver Report, Compared Between the Epo and Placebo Groups.
Time frame: Through 22-26 months
Number of Participants Experiencing Cortical Visual Impairment, Per Parent/Caregiver Report, Compared Between the Epo and Placebo Groups.
Time frame: Through 22-26 months
| Milestone | Erythropoietin | Placebo |
|---|---|---|
| Started | 257 | 243 |
| Completed | 240 | 222 |
| Not completed | 17 | 21 |
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
| Participants | Erythropoietin | Placebo |
|---|---|---|
| Number of Participants With Death or Neurodevelopmental Impairment | 126 | 110 |
Neurologic diagnoses: no CP, diparetic CP, hemiparetic CP, quadriparetic CP
| Participants | Erythropoietin | Placebo |
|---|---|---|
| No cerebral palsy | 176 | 173 |
| Diparetic cerebral palsy | 9 | 6 |
| Hemiparetic cerebral palsy | 3 | 2 |
| Quadriparetic cerebral palsy | 19 | 17 |
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.
| Participants | Erythropoietin | Placebo |
|---|---|---|
| GMFCS = 0 | 186 | 178 |
| GMFCS = 0.5 | 6 | 6 |
| GMFCS = 1 | 4 | 6 |
| GMFCS = 2 | 3 | 5 |
| GMFCS = 3 | 2 | 1 |
| GMFCS = 4 | 4 | 1 |
| GMFCS = 5 | 6 | 7 |
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.
| score on a scale | Erythropoietin | Placebo |
|---|---|---|
| Bayley III Cognitive Score | 89.1 ± 15.7 | 89.5 ± 17.5 |
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.
| score on a scale | Erythropoietin | Placebo |
|---|---|---|
| Bayley III Language Score | 87.9 ± 20.4 | 86.7 ± 20.8 |
≥ 2 afebrile, unprovoked seizures
| Participants | Erythropoietin | Placebo |
|---|---|---|
| Number of Participants With Epilepsy | 5 | 4 |
Score for externalizing problems on Childhood Behavior Checklist of \>= 65
| Participants | Erythropoietin | Placebo |
|---|---|---|
| Number of Participants With Behavioral Abnormalities Determined by the Externalizing Score of the Child Behavior Checklist | 15 | 3 |
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.
| Participants | Erythropoietin | Placebo |
|---|---|---|
| Normal | 114 | 112 |
| Mild motor and/or cognitive impairment | 26 | 23 |
| Moderate/severe impairment | 63 | 59 |
| Death | 37 | 28 |
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Epo level at baseline, day 2, and day 4.
| mU/ml | Erythropoietin | Placebo |
|---|---|---|
| Baseline | 32.7 (13.5 to 183.4) | 36.0 (12.3 to 96.7) |
| Day 2 | 1530 (1259 to 5802) | 34.4 (18.0 to 91.9) |
| Day 4 | 2682 (2190 to 4637) | 20.5 (8.1 to 54.7) |
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).
| score on a scale | Erythropoietin | Placebo |
|---|---|---|
| MR Evidence of Brain Injury - Brain Injury Score | 8 (2 to 26) | 7 (2 to 20) |
| Participants | Erythropoietin | Placebo |
|---|---|---|
| None | 49 | 51 |
| Mild | 91 | 86 |
| Moderate | 46 | 51 |
| Severe | 56 | 43 |
| Participants | Erythropoietin | Placebo |
|---|---|---|
| Number of Participants Experiencing Hearing Impairment Requiring Hearing Aids, Per Parent/Caregiver Report, Compared Between the Epo and Placebo Groups. | 10 | 13 |
| Participants | Erythropoietin | Placebo |
|---|---|---|
| Number of Participants Experiencing Cortical Visual Impairment, Per Parent/Caregiver Report, Compared Between the Epo and Placebo Groups. | 19 | 20 |
Collected over 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.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Erythropoietin | 37/257 (14.4%) | 137/257 (53.3%) | 254/257 (98.8%) |
| Placebo | 28/243 (11.5%) | 106/243 (43.6%) | 240/243 (98.8%) |
| Event | Erythropoietin | Placebo |
|---|---|---|
| Intracranial hemorrhageBlood and lymphatic system disorders | 68/257 | 55/243 |
| Pulmonary hypertensionCardiac disorders | 51/257 | 36/243 |
| Disseminated intravascular coagulationBlood and lymphatic system disorders | 39/257 | 25/243 |
| DeathGeneral disorders | 37/257 | 28/243 |
| Other unexpected life threatening eventGeneral disorders | 10/257 | 6/243 |
| Systemic hypertensionCardiac disorders | 7/257 | 7/243 |
| Major venous or arterial thrombosisBlood and lymphatic system disorders | 6/257 | 3/243 |
| Cardiopulmonary arrestCardiac disorders | 3/257 | 3/243 |
| PolycythemiaBlood and lymphatic system disorders | 0/257 | 0/243 |
| Event | Erythropoietin | Placebo |
|---|---|---|
| Ever intubatedRespiratory, thoracic and mediastinal disorders | 206/257 | 195/243 |
| Acute liver injuryHepatobiliary disorders | 125/257 | 111/243 |
| ThrombocytopeniaBlood and lymphatic system disorders | 115/257 | 88/243 |
| Seizure: clinical or electrographicNervous system disorders | 88/257 | 97/243 |
| Hypotension warranting inotropesCardiac disorders | 90/257 | 73/243 |
| Discharged alive - abnormal neurologic examinationNervous system disorders | 50/257 | 58/243 |
| Meconium aspiration systemRespiratory, thoracic and mediastinal disorders | 46/257 | 49/243 |
| Intubated > 7 daysRespiratory, thoracic and mediastinal disorders | 49/257 | 38/243 |
| Acute kidney injuryRenal and urinary disorders | 35/257 | 23/243 |
| NeutropeniaBlood and lymphatic system disorders | 24/257 | 17/243 |
| Age, Continuous(years) | Erythropoietin | Placebo | Total |
|---|---|---|---|
| Mean | 29.6 ± 6.3 | 30.0 ± 6.6 | 29.6 ± 6.3 |
| Sex: Female, Male(Participants) | Erythropoietin | Placebo | Total |
|---|---|---|---|
| Female | 122 | 103 | 225 |
| Male | 135 | 140 | 275 |
| Ethnicity (NIH/OMB)(Participants) | Erythropoietin | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 63 | 59 | 122 |
| Not Hispanic or Latino | 194 | 184 | 378 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Erythropoietin | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 18 | 15 | 33 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 28 | 38 | 66 |
| White | 183 | 173 | 356 |
| More than one race | 10 | 6 | 16 |
| Unknown or Not Reported | 18 | 11 | 29 |
| Region of Enrollment(participants) | Erythropoietin | Placebo | Total |
|---|---|---|---|
| United States | 257 | 243 | 500 |
| Maternal education, high school or less(Participants) | Erythropoietin | Placebo | Total |
|---|---|---|---|
| Count of participants | 102 | 83 | 185 |
| Parity of 1, including trial infant(Participants) | Erythropoietin | Placebo | Total |
|---|---|---|---|
| Count of participants | 145 | 141 | 286 |
| Pregnancy and delivery complications - maternal chorioamnionitis or fever(Participants) | Erythropoietin | Placebo | Total |
|---|---|---|---|
| Count of participants | 45 | 32 | 77 |
19 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes
Ran from Jan 2017 to primary completion in Oct 2021, 57 months.
Results were first posted in Jan 2023, 1 year 3 months after primary completion.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Erythropoietin
University of California, San Francisco →