Anemia, Congenital Heart Disease, Cyanosis, Cyanotic Congenital Heart Disease
Conditions
Keywords
Erythropoetin, Cyanotic Heart Disease, Transfusion, Congenital Heart Disease
Brief summary
Cyanotic congenital cardiac patients require higher hemoglobin concentrations (red blood cell levels) for optimal oxygen delivery to the body. Prophylactic erythropoietin (EPO) and iron can prevent and/or decrease the amount of blood transfusions needed in this population. We seek to investigate if EPO and iron make a clinically significant difference in the number of transfusions given to these patients and the morbidity associated with it.
Detailed description
Congenital heart disease occurs in about 1% of all live births. Cyanotic cardiac lesions in particular are at risk for significant mortality and morbidity because of their reduced ability to provide adequate oxygenation to the body and the brain. Many experts believe that to have adequate oxygen carrying capacity that these infants should ideally have a hemoglobin level greater than 13 g/dL. Many of these patients require blood transfusions prior to surgery to provide adequate oxygenation. The cause for this is likely multifactorial including normal neonatal physiology, frequent lab draws, and co-morbidities. Although rare, the morbidity due to transfusions can be devastating to this population including transmitted infections, transfusion reactions, extra hospitalizations, and antigen sensitization that would complicate heart transplant if needed. There are centers in the United States that have developed protocols using erythropoietin to minimize blood product transfusions before and after surgery, also referred to as bloodless surgery. There have been retrospective studies evaluating the success of these protocols, but there are no randomized controlled prospective studies that the investigators have studying the effects of erythropoietin effects in patients with cyanotic heart disease in regards to transfusion prevention. Congenital cyanotic cardiac patients require higher hemoglobin concentrations for optimal oxygen delivery. Prophylactic erythropoietin can prevent and/or decrease the amount of blood transfusions needed prior to surgery. The researchers seek to investigate if erythropoietin makes a clinically significant difference in the number of transfusions given to these patients and the morbidity associated with it.
Interventions
DRUGEpoetin Alfa and Iron
Patients in the treatment group will receive weekly EPO injections and iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization) They will be followed for 14 weeks.
DRUGIron
Patients in the treatment group will not receive any extra intervention outside of standard of care. They will receive iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization). They will be followed for 14 weeks.
Sponsors
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 8 Weeks
Healthy volunteers
No
Inclusion criteria
* Newborns less than 4 weeks old at diagnosis * Gestational age \>34 weeks * Birth weight 2.2-4kg * Cyanotic heart disease who have had a surgical shunt or a catheterization intervention that is equivalent to a shunt (patent ductus arteriosus stent, right ventricular outflow tract stent). * Baseline hematocrit to be below \<40%. * Completes at least 1 injection in the study by 8 weeks of age.
Exclusion criteria
* Infants diagnosed at greater than 4 weeks of age * Gestation \<34 weeks * Birth weight \<2.2 kg or \>4kg * Hematocrit \>40% * Newborns with acyanotic heart disease * Infants with significant co-morbidities: * Renal failure (Creatinine \> 2 standard deviations above age adjusted norm) * Hepatic failure (elevated AST/ALT levels \> 2 standard deviations above age adjusted norm * Hemolytic disease * Hemoglobinopathies (Sickle-cell disease, Thalassemias)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Transfusions Needed | First 4 months of life | Prophylactic erythropoietin can prevent and/or decrease the amount of blood transfusions needed prior to surgery. We seek to investigate if erythropoietin makes a clinically significant difference in the number of transfusions given to these patients and the morbidity associated with it during the period in which the subjects will be active in the study (from baseline to 14 weeks post initial injection). The primary aim will be assessed when all subjects have completed week 14 or discontinue early. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oxygen Saturation | First 4 months of life | Often, cyanotic congenital heart defect neonates have prolonged initial hospital stays due to the inability to maintain acceptable oxygen saturations, and transition to adequate oral intake for appropriate weight gain. If the hospital stay is found to be shortened after starting erythropoietin, this may be of clinical and financial significance. |
| Number of Hospitalizations | First 4 months of life | The number of hospital readmissions (related to failure to thrive or cyanosis) may imply the overall clinical stability of a patient. Because these infants are at high risk for mortality at home, there are multiple reasons why they may be admitted to the hospital including clinically significant anemia which requires blood transfusions, poor weight gain, difficulty feeding, inadequate oxygen saturations, and illnesses. Each admission is stressful to the patient and their families. Having a normal hemoglobin level may have a role in preventing several of these factors, especially regarding failure to thrive or cyanosis. |
| Weight Gain | First 4 months of life | The secondary outcome of weight gain is appropriate in the setting of infants as this variable has been used to monitor the ability to thrive and meet the body's metabolic demands. It is well established in pediatrics that the neonate and infant should gain 15-30 grams per day for optimal growth. Infants who are cyanotic already have a deficiency in meeting their metabolic demands due to a reduced oxygen carrying capacity. This is further complicated in the instance of anemia. Thus, infants may have an increased ability to optimize weight gain in the setting of normal, stable hemoglobin levels which may be achieved with erythropoietin. |
| Time to Initial Discharge | First 4 months of life | If the hospital stay is found to be shortened after starting erythropoietin, this may be of clinical and financial significance. |
Countries
United States
Participant flow
Pre-assignment details
4 Patients who had been screened/consented for the study did not reach the minimum hematocrit threshold for enrollment and were therefore screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Control Group II (non-treatment group): Patients in the treatment group will not receive any extra intervention outside of standard of care. They will receive iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization). They will be followed for 14 weeks.
Iron: Patients in the treatment group will not receive any extra intervention outside of standard of care. They will receive iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization). They will be followed for 14 weeks. | 2 |
| Epoetin Alfa and Iron Supplements Group I (treatment group): Patients in the treatment group will receive weekly EPO injections and iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization) They will be followed for 14 weeks.
Epoetin Alfa and Iron: Patients in the treatment group will receive weekly EPO injections and iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization) They will be followed for 14 weeks. | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 2 | 2 |
Baseline characteristics
| Characteristic | Epoetin Alfa and Iron Supplements | Total | Control |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 4 Participants | 2 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Transfusions Needed
Prophylactic erythropoietin can prevent and/or decrease the amount of blood transfusions needed prior to surgery. We seek to investigate if erythropoietin makes a clinically significant difference in the number of transfusions given to these patients and the morbidity associated with it during the period in which the subjects will be active in the study (from baseline to 14 weeks post initial injection). The primary aim will be assessed when all subjects have completed week 14 or discontinue early.
Time frame: First 4 months of life
Population: The principal investigator discussed the study's future with the sub-investigators on the study and came to the conclusion to close the study due to low enrollment while also considering the financial costs to continue to run the study.
Secondary
Number of Hospitalizations
The number of hospital readmissions (related to failure to thrive or cyanosis) may imply the overall clinical stability of a patient. Because these infants are at high risk for mortality at home, there are multiple reasons why they may be admitted to the hospital including clinically significant anemia which requires blood transfusions, poor weight gain, difficulty feeding, inadequate oxygen saturations, and illnesses. Each admission is stressful to the patient and their families. Having a normal hemoglobin level may have a role in preventing several of these factors, especially regarding failure to thrive or cyanosis.
Time frame: First 4 months of life
Population: The principal investigator discussed the study's future with the sub-investigators on the study and came to the conclusion to close the study due to low enrollment while also considering the financial costs to continue to run the study.
Secondary
Oxygen Saturation
Often, cyanotic congenital heart defect neonates have prolonged initial hospital stays due to the inability to maintain acceptable oxygen saturations, and transition to adequate oral intake for appropriate weight gain. If the hospital stay is found to be shortened after starting erythropoietin, this may be of clinical and financial significance.
Time frame: First 4 months of life
Population: The principal investigator discussed the study's future with the sub-investigators on the study and came to the conclusion to close the study due to low enrollment while also considering the financial costs to continue to run the study.
Secondary
Time to Initial Discharge
If the hospital stay is found to be shortened after starting erythropoietin, this may be of clinical and financial significance.
Time frame: First 4 months of life
Population: The principal investigator discussed the study's future with the sub-investigators on the study and came to the conclusion to close the study due to low enrollment while also considering the financial costs to continue to run the study.
Secondary
Weight Gain
The secondary outcome of weight gain is appropriate in the setting of infants as this variable has been used to monitor the ability to thrive and meet the body's metabolic demands. It is well established in pediatrics that the neonate and infant should gain 15-30 grams per day for optimal growth. Infants who are cyanotic already have a deficiency in meeting their metabolic demands due to a reduced oxygen carrying capacity. This is further complicated in the instance of anemia. Thus, infants may have an increased ability to optimize weight gain in the setting of normal, stable hemoglobin levels which may be achieved with erythropoietin.
Time frame: First 4 months of life
Population: The principal investigator discussed the study's future with the sub-investigators on the study and came to the conclusion to close the study due to low enrollment while also considering the financial costs to continue to run the study.