RED-HF™ Trial - Reduction of Events With Darbepoetin Alfa in Heart Failure Trial

• To evaluate the effects of treatment with darbepoetin alfa on time to death from any cause [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
• To evaluate the effects of treatment with darbepoetin alfa on time to cardiovascular death or first hospital admission for worsening HF, whichever occurs first [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
• To evaluate the effects of treatment with darbepoetin alfa on change from baseline to month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score [ Time Frame: Six months ] [ Designated as safety issue: No ]
• To evaluate the effects of treatment with darbepoetin alfa on change from baseline to month 6 in KCCQ Symptom Frequency Score [ Time Frame: Six months ] [ Designated as safety issue: No ]

• "To evaluate the effects of treatment with darbepoetin alfa on:
• time to death from any cause
• time to cardiovascular death or first hospital admission for worsening HF, whichever occurs first
• change from baseline to month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
• change from baseline to month 6 in KCCQ Symptom Frequency Score

The purpose of the study is to determine the efficacy of treatment of anemia with darbepoetin alfa compared to placebo on the composite of time to death from any cause or first hospital admission for worsening HF in subjects with symptomatic left ventricular systolic dysfunction and anemia.

Several epidemiological studies have demonstrated an association between HF and anemia and correlation of increased risk for mortality and hospitalization with low hemoglobin in patients with HF. Earlier single-center interventional studies suggest that meaningful clinical benefits may be achieved by raising hemoglobin concentration in patients with symptomatic HF and anemia. Data from Amgen's completed phase 2 multi-center studies support this hypothesis and show that darbepoetin alfa is well tolerated in patients with symptomatic left ventricular systolic dysfunction and anemia and effectively raises hemoglobin. The pivotal phase 3 Study 20050222 RED-HF Trial is evaluating the effect of treatment with darbepoetin alfa on the composite risk of all-cause mortality or hospitalization for worsening HF in subjects with symptomatic left ventricular systolic dysfunction and anemia. This study also evaluates the effect of darbepoetin alfa treatment on all-cause death, on cardiovascular death or hospitalization for worsening HF, and on patient-reported quality-of-life outcomes.

• Heart Failure
• Anemia
• Cardiovascular Disease
• Ventricular Dysfunction
• Congestive Heart Failure

• Drug: Darbepoetin alfa

  Starting dose: 0.75 mcg/kg subcutaneously Q2W

  Subsequent doses:

  - Darbepoetin alfa group to receive darbepoetin alfa titrated to achieve Hb target of 13.0 g/dL, not to exceed 14.5 g/dL

• Drug: Placebo
  Placebo group to receive volume and dose frequency changes resembling titration dosing in the treatment group

• Experimental: Active
  Intervention: Drug: Darbepoetin alfa
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• McMurray JJ, Anand IS, Diaz R, Maggioni AP, O'Connor C, Pfeffer MA, Polu KR, Solomon SD, Sun Y, Swedberg K, Tendera M, van Veldhuisen DJ, Wasserman SM, Young JB; RED-HF Committees and Investigators. Design of the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF): a Phase III, anaemia correction, morbidity-mortality trial. Eur J Heart Fail. 2009 Aug;11(8):795-801.
• Swedberg K, Young JB, Anand IS, Cheng S, Desai AS, Diaz R, Maggioni AP, McMurray JJ, O'Connor C, Pfeffer MA, Solomon SD, Sun Y, Tendera M, van Veldhuisen DJ; RED-HF Committees; RED-HF Investigators. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013 Mar 28;368(13):1210-9. doi: 10.1056/NEJMoa1214865. Epub 2013 Mar 10.

Inclusion Criteria:

• HF of at least 3 months duration and of NYHA class II, III, or IV
• hemoglobin between 9.0 g/dL and 12.0 g/dL
• left ventricular ejection fraction equal to or less than 40%

Exclusion Criteria:

• Transferrin saturation (Tsat) < 15%
• Blood pressure > 160/100 mm Hg
• Heart failure primarily due to valvular heart disease or clinically significant valvular heart disease that might lead to surgical correction within 12 months of randomization
• Recipient of a major organ transplant or receiving renal replacement therapy
• Serum creatinine > 3.0 mg/dL (> 265 µmol/L)