Clinical trial NCT02564796: Erythropoietin to Prevent Unnecessary Transfusions In Patients With Cyanotic CHD - A Prospective Control Trial
Official title: Erythropoietin to Prevent Unnecessary Transfusions In Patients With Cyanotic Congenital Heart Disease - A Prospective Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cyanotic Congenital Heart Disease
Anemia
Cyanosis
Congenital Heart Disease
Keywords: Erythropoetin
Cyanotic Heart Disease
Transfusion
Congenital Heart Disease
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2015-10-01
Enrollment: 4
Sex: ALL
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Transfusions Needed
timeFrame: First 4 months of life
Secondary outcomes:
measure: Oxygen Saturation
timeFrame: First 4 months of life
measure: Number of Hospitalizations
timeFrame: First 4 months of life
measure: Weight Gain
timeFrame: First 4 months of life
measure: Time to Initial Discharge
timeFrame: First 4 months of life
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
Study officials:
affiliation: University of California, San Diego/Rady Children's Hospital San Diego
name: David K Werho, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Donato H. Erythropoietin: an update on the therapeutic use in newborn infants and children. Expert Opin Pharmacother. 2005 May;6(5):723-34. doi: 10.1517/14656566.6.5.723.
citation: Fearon JA, Weinthal J. The use of recombinant erythropoietin in the reduction of blood transfusion rates in craniosynostosis repair in infants and children. Plast Reconstr Surg. 2002 Jun;109(7):2190-6. doi: 10.1097/00006534-200206000-00002.
citation: Maier RF, Obladen M, Muller-Hansen I, Kattner E, Merz U, Arlettaz R, Groneck P, Hammer H, Kossel H, Verellen G, Stock GJ, Lacaze-Masmonteil T, Claris O, Wagner M, Matis J, Gilberg F; European Multicenter Erythropoietin Beta Study Group. Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g. J Pediatr. 2002 Jul;141(1):8-15. doi: 10.1067/mpd.2002.124309.
citation: Richard S, Brion JP, Couck AM, Flament-Durand J. Accumulation of smooth endoplasmic reticulum in Alzheimer's disease: new morphological evidence of axoplasmic flow disturbances. J Submicrosc Cytol Pathol. 1989 Jul;21(3):461-7.