Congenital Heart Defect
Conditions
Keywords
Erythropoietin, Congenital heart surgery
Brief summary
Lack of bloodflow to the heart and brain when the heart is stopped during heart surgery can cause damage to those organs. We hypothesize that a single dose of erythropoietin prior to the heart bypass portion of surgery may protect the infant human heart and brain from injury. This randomized clinical trial will involve 120 children, age 6 weeks to 18 years, requiring heart bypass surgery for congenital heart defects.
Detailed description
Lack of bloodflow to the heart and brain when the heart is stopped during heart surgery can cause damage to those organs. A medicine already used in humans, erythropoietin, may protect the heart and brain of children born with heart defects during their surgical repair. In a rabbit model, erythropoietin did protect the hearts. We hypothesize that a single dose of erythropoietin prior to the heart bypass portion of surgery may protect the infant human heart and brain from injury. For this randomized control trial, 120 children, age 6 weeks to 18 years, requiring heart bypass surgery for congenital heart defects, will be divided into four groups. Two groups will be children whose usual blood oxygen level is low because of their heart defect; the other two will be children with normal blood oxygen levels. Each child will be randomized to receive either erythropoietin or placebo 15 minutes prior to stopping the heart during their surgery. Erythropoietin's protective function will be measured after surgery by: (1) amount of medication required to support heart function, (2) how well the heart pumps blood as seen by echocardiogram, (3) levels of chemicals produced by the body when heart or brain tissue injury occurs, (4) urine output and oxygen levels (5) time on ventilator support (6) ICU stay and (7) hospital stay. Heart tissue will be collected during surgery to determine how erythropoietin protects heart cells. Statistical tests including ANOVA will test for similarities and differences among the groups on the measures of protection from injury. Note - the study design was edited after the FDA released a warning about the use of erythropoietin. Only acyanotic patients were recruited therefore only 2 study groups are included.
Interventions
DRUGacyanotic erythropoietin
Single dose IV push
DRUGacyanotic placebo
Single dose IV push
Sponsors
Children's Hospital and Health System Foundation, Wisconsin
National Center for Research Resources (NCRR)
Medical College of Wisconsin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 18 Years
Healthy volunteers
No
Inclusion criteria
* Age 6 weeks to 18 years * Requiring open heart surgery for congenital heart defect -Parents able to speak English and document informed consent -
Exclusion criteria
* Received erythropoietin within past 30 days * Previous adverse reaction to erythropoietin or to albumin * History of neurological disorder -Laboratory evidence of kidney or liver dysfunction -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical Markers of Heart Damage | 4 postoperative time points up to 48 hours | Troponin I levels (ng/ml) measured at 4 time points |
| Biochemical Markers of Neuron Damage | 4 postoperative time points | — |
| Echocardiographic Assessment of Heart Function | 24 hours postop | — |
Secondary
| Measure | Time frame |
|---|---|
| Inotropic Support | 24 and 48 hours post operative |
| Length of Hospitalization | At hospital discharge, up to 30 days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acyanotic Placebo Children requiring cardiac surgery with cardiopulmonary bypass with baseline saturations greater than 88% \_ Received placebo | 3 |
| Acyanotic Study Drug Children requiring cardiac surgery with cardiopulmonary bypass with baseline saturations greater than 88% - Received study drug | 6 |
| Total | 9 |
Baseline characteristics
| Characteristic | Acyanotic Study Drug | Acyanotic Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 3 Participants | 9 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 12.9 years STANDARD_DEVIATION 4.5 | 3.1 years STANDARD_DEVIATION 1.2 | 9.6 years STANDARD_DEVIATION 6.1 |
| Region of Enrollment United States | 6 participants | 3 participants | 9 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 3 | 0 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 6 |
Outcome results
Primary
Biochemical Markers of Heart Damage
Troponin I levels (ng/ml) measured at 4 time points
Time frame: 4 postoperative time points up to 48 hours
Population: Analysis was limited to descriptive statistics due to low enrollment and study closure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acyanotic Placebo | Biochemical Markers of Heart Damage | 60 minutes post bypass | 31.1 ng/ml | Standard Deviation 12.2 |
| Acyanotic Placebo | Biochemical Markers of Heart Damage | 4 hrs post bypass | 27.2 ng/ml | Standard Deviation 8.6 |
| Acyanotic Placebo | Biochemical Markers of Heart Damage | 24 hrs post bypass | 10 ng/ml | Standard Deviation 6.2 |
| Acyanotic Placebo | Biochemical Markers of Heart Damage | 48 hrs post bypass | 5.2 ng/ml | Standard Deviation 1.9 |
| Acyanotic Study Drug | Biochemical Markers of Heart Damage | 48 hrs post bypass | 5.2 ng/ml | Standard Deviation 5.2 |
| Acyanotic Study Drug | Biochemical Markers of Heart Damage | 60 minutes post bypass | 12.3 ng/ml | Standard Deviation 9.2 |
| Acyanotic Study Drug | Biochemical Markers of Heart Damage | 24 hrs post bypass | 10.7 ng/ml | Standard Deviation 10.4 |
| Acyanotic Study Drug | Biochemical Markers of Heart Damage | 4 hrs post bypass | 15 ng/ml | Standard Deviation 8.2 |
Primary
Biochemical Markers of Neuron Damage
Time frame: 4 postoperative time points
Population: There were 43 samples taken from the 9 subjects but no analysis was performed - the laboratory did not set up the assay to run the samples because the study did not have enough subjects to achieve statistical power.
Primary
Echocardiographic Assessment of Heart Function
Time frame: 24 hours postop
Population: These data were not collected.
Secondary
Inotropic Support
Time frame: 24 and 48 hours post operative
Population: These data were not collected
Secondary
Length of Hospitalization
Time frame: At hospital discharge, up to 30 days
Population: Analysis was limited to descriptive statistics due to low enrollment and study closure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acyanotic Placebo | Length of Hospitalization | 4.6 days | Standard Deviation 1.2 |
| Acyanotic Study Drug | Length of Hospitalization | 6 days | Standard Deviation 5.2 |