Moderate or Severe Hypoxic-ischemic Encephalopathy in Newborns
Conditions
Keywords
Hypoxic-ischemic encephalopathy, autologous cord blood cells, newborn infants
Brief summary
This study will test the safety and efficacy of an infusion of a baby's own (autologous) umbilical cord blood as compared with placebo in babies born with history and signs of hypoxic-ischemic brain injury.
Detailed description
The purpose of this phase II study is to assess the safety and efficacy of up to two intravenous infusions of autologous volume and red blood cell reduced nucleated umbilical cord blood cells as compared with placebo in neonates with neonatal encephalopathy undergoing hypothermia treatment. Efficacy will be estimated by one year survival and score on Bayley III scores in all three domains equal to or greater than 85. This will be a randomized, double-blind, placebo controlled multi-site trial of up to 160 infants who qualify for cooling.
Interventions
BIOLOGICALInfusion of autologous cord blood
Infants who meet study enrollment criteria will receive up to 2 infusions of their own volume reduced cord blood cells. The number of doses will be determined by the amount of available cord blood cells.
BIOLOGICALPlacebo
Infants who meet study enrollment criteria will receive up to 2 placebo infusions composed of an equivalent volume (volume of product that would have been administered if the infant randomized to the intervention arm) of packed red blood cells (PRBCs) from the red cell compartment of the separated cord blood unit.
Sponsors
The Robertson Foundation
Michael Cotten
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
0 Hours to 6 Hours
Healthy volunteers
No
Inclusion criteria
1. NICHD Neonatal Research Network Hypothermia Trial inclusion criteria 2. Mothers must have consented or given verbal assent for cord blood collection at delivery, and cord blood must be available for volume and red blood cell reduction before 45 hours of age 3. The infant must be able to receive at least one dose of autologous cord blood before 48 hours of age 4. All infants must have signs of encephalopathy within 6 hours of age
Exclusion criteria
1. Major congenital or chromosomal abnormalities 2. Severe growth restriction (birth weight \<1800 g) 3. Opinion by attending neonatologist that the study may interfere with treatment or safety of subject 4. Moribund neonates for whom no further treatment is planned 5. Infants born to mothers are known to be HIV, Hepatitis B, Hepatitis C or who have active syphilis or CMV infection in pregnancy 6. Infants suspected of overwhelming sepsis 7. ECMO initiated or likely in the first 48 hours of life
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival at One Year | 1 year | Number of participants alive at one year. |
| Number of Participants With Bayley III Scores in All Three Domains > or Equal to 85 | 1 year | The Bayley is a standardized, norm-referenced measure that assesses development in Cognitive, Language and Motor domains. Composite standard scores can be derived that have a mean of 100 and a standard deviation of 15. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Require iNO (Inhaled Nitric Oxide) Use | During hospitalization, approximately 4-92 days | — |
| Number of Subjects Who Require ECMO | During hospitalization, approximately 4-92 days | ECMO (extracorporeal membrane oxygenation) is a technique of providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequate amount of gas exchange or perfusion to sustain life. |
| Mortality Rate | 1 year | (Number of participants who died/total number of participants) x 100 |
| Number of Subjects Who Are Discharged on Anti-epileptic Medication | At hospital discharge, approximately 4-92 days | — |
| Number of Subjects Who Require Gastrostomy Tube (G-tube) Feeding | During hospitalization, approximately 4-92 days | — |
| Number of Subjects Who Experience Seizures | During hospitalization, approximately 4-92 days | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Cell Recipients Experimental: infusions: infants with moderate to severe hypoxic ischemic encephalopathy, begin cooling, and have autologous nucleated cord blood cells available for infusion will receive up to two infusions. Outcomes will be measured at 22-26 months by neurodevelopment assessment
Infusion of autologous cord blood: Infants who meet study enrollment criteria will receive up to 2 infusions of their own volume reduced cord blood cells. The number of doses will be determined by the amount of available cord blood cells. | 17 |
| Placebo Recipients Control: infants with moderate to severe hypoxic ischemic encephalopathy, begin cooling, and have cord blood available for infusion will receive placebo (a mix of autologous cord blood red blood cells and plasma) infusions. Outcomes will be measured at 22-26 months by neurodevelopment assessment
Placebo: Infants who meet study enrollment criteria will receive up to 2 placebo infusions composed of an equivalent volume (volume of product that would have been administered if the infant randomized to the intervention arm) of packed red blood cells (PRBCs) from the red cell compartment of the separated cord blood unit. | 18 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 2 |
Baseline characteristics
| Characteristic | Intervention Cell Recipients | Placebo Recipients | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 17 Participants | 18 Participants | 35 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 17 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 8 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) White | 8 Participants | 7 Participants | 15 Participants |
| Region of Enrollment United States | 17 Participants | 18 Participants | 35 Participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 17 | 1 / 18 |
| other Total, other adverse events | 1 / 17 | 3 / 18 |
| serious Total, serious adverse events | 1 / 17 | 2 / 18 |
Outcome results
Primary
Number of Participants With Bayley III Scores in All Three Domains > or Equal to 85
The Bayley is a standardized, norm-referenced measure that assesses development in Cognitive, Language and Motor domains. Composite standard scores can be derived that have a mean of 100 and a standard deviation of 15.
Time frame: 1 year
Population: Participants with known one year outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Cell Recipients | Number of Participants With Bayley III Scores in All Three Domains > or Equal to 85 | 12 Participants |
| Placebo Recipients | Number of Participants With Bayley III Scores in All Three Domains > or Equal to 85 | 6 Participants |
p-value: 0.06Fisher Exact
Primary
Survival at One Year
Number of participants alive at one year.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Cell Recipients | Survival at One Year | 16 Participants |
| Placebo Recipients | Survival at One Year | 17 Participants |
Secondary
Mortality Rate
(Number of participants who died/total number of participants) x 100
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention Cell Recipients | Mortality Rate | 5.88 percentage of participants |
| Placebo Recipients | Mortality Rate | 5.56 percentage of participants |
Secondary
Number of Subjects Who Are Discharged on Anti-epileptic Medication
Time frame: At hospital discharge, approximately 4-92 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Cell Recipients | Number of Subjects Who Are Discharged on Anti-epileptic Medication | 2 Participants |
| Placebo Recipients | Number of Subjects Who Are Discharged on Anti-epileptic Medication | 1 Participants |
Secondary
Number of Subjects Who Experience Seizures
Time frame: During hospitalization, approximately 4-92 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Cell Recipients | Number of Subjects Who Experience Seizures | 6 Participants |
| Placebo Recipients | Number of Subjects Who Experience Seizures | 6 Participants |
Secondary
Number of Subjects Who Require ECMO
ECMO (extracorporeal membrane oxygenation) is a technique of providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequate amount of gas exchange or perfusion to sustain life.
Time frame: During hospitalization, approximately 4-92 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Cell Recipients | Number of Subjects Who Require ECMO | 0 Participants |
| Placebo Recipients | Number of Subjects Who Require ECMO | 0 Participants |
Secondary
Number of Subjects Who Require Gastrostomy Tube (G-tube) Feeding
Time frame: During hospitalization, approximately 4-92 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Cell Recipients | Number of Subjects Who Require Gastrostomy Tube (G-tube) Feeding | 2 Participants |
| Placebo Recipients | Number of Subjects Who Require Gastrostomy Tube (G-tube) Feeding | 3 Participants |
Secondary
Number of Subjects Who Require iNO (Inhaled Nitric Oxide) Use
Time frame: During hospitalization, approximately 4-92 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Cell Recipients | Number of Subjects Who Require iNO (Inhaled Nitric Oxide) Use | 3 Participants |
| Placebo Recipients | Number of Subjects Who Require iNO (Inhaled Nitric Oxide) Use | 2 Participants |