Erythropoietin to Prevent Unnecessary Transfusions In Patients With Cyanotic CHD - A Prospective Control Trial

NCT ID: NCT02564796

Last Updated: 2021-12-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2020-06-30

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.

Conditions

Cyanotic Congenital Heart Disease; Anemia; Cyanosis; Congenital Heart Disease

Keywords

Erythropoetin; Cyanotic Heart Disease; Transfusion; Congenital Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Iron

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Epoetin Alfa and Iron

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

No other name; No other name

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)

• Maximum Eligible Age: 8 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

David Werho, MD

Assistant Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David K Werho, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego/Rady Children's Hospital San Diego

Locations

Rady Children's Hospital

San Diego, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 15934899 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12045535 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12091844 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2477140 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

160871

Identifier Type: -

Identifier Source: org_study_id