Frequent, Low-Dose Erythropoietin A Mechanistic Approach to Mitigate Adverse Cardiovascular Effects of Erythropoietin

• Status: Terminated
• Trial end date: 2019-06-03
• Target enrollment: 0
• Participant gender: All

Summary

Although several large well designed clinical trials have shown that erythropoietin which is commonly used to treat anemia associated with kidney disease, increases the risk of stroke and heart disease, the mechanism for this increased risk is unknown. The investigators' preliminary studies show that the adverse effects of erythropoietin are from activation of the heterodimeric erythropoietin/ beta common receptor which only occurs with high doses of erythropoietin. The investigators propose a clinical trial of 120 patients assigned to low doses of erythropoietin given more frequently or the same cumulative dose of erythropoietin administered as a high dose once every two weeks and assess effects on the beta common receptor activation, inflammation and vascular disease as evidence by MRI of the carotid arteries.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VA Office of Research and Development
• Treatments: Epoetin Alfa

Criteria

Inclusion Criteria:

The investigators will enroll Veterans who fulfill the following criteria:

• stage 3, 4, or 5 CKD (estimated glomerular filtration rate of less than 60 ml/min/1.73 m2) on at least two separate occasions greater than 3 months apart; and

• candidates for EPO therapy as per the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative guidelines (hemoglobin < 10 gm/dL and anemia of CKD).

Exclusion Criteria:

The investigators will exclude any Veteran who meets any of the following criteria:

1. pregnant, planning to become pregnant in the next year, or breast feeding;

2. uncontrolled hypertension (blood pressure > 180/100 mm Hg despite optimal antihypertensive medications);

3. active gastrointestinal bleeding (visible blood or positive tests for stool occult blood accompanied by a decrease in hemoglobin);

4. likely to have EPO resistance;

5. an adverse cardiovascular event in the prior three months;

6. active or recent (within the last 3 months) severe, systemic infection;

7. active inflammatory disease such as lupus, rheumatoid arthritis, or vasculitis requiring immunosuppressive or immunomodulatory medications;

8. history of solid organ transplantation;

9. expected off-dialysis survival of less than one year (as determined by the estimated glomerular filtration slope and the treating physician;

10. active cancer (undergoing chemotherapy or radiation within the last 3 months) or primary bone marrow disease such as myelofibrosis; or

11. a contraindication for an MRI or individuals who cannot comply with the study protocol. The investigators will exclude healthy subjects that meet a, b, f, g, h, or j.