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

Phase 3

Completed

Conditions: Congestive Heart Failure
Ventricular Dysfunction
Heart Failure
Anemia
Cardiovascular Disease

Interventions: Drug: Darbepoetin alfa
Drug: Placebo

Registration Number: NCT00358215

Lead Sponsor: Amgen

Brief Summary: 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 heart failure in patients with symptomatic left ventricular systolic dysfunction and anemia.

Detailed Description: 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 patients 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2278

Inclusion Criteria

Heart failure of at least 3 months duration and of New York Heart Association (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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Darbepoetin alfa	Darbepoetin alfa	Starting dose of 0.75 µg/kg subcutaneously every 2 weeks until hemoglobin concentrations reach 13.0 g/dL on 2 consecutive visits, then monthly dosing, titrated to achieve hemoglobin target of 13.0 g/dL, not to exceed 14.5 g/dL.
Placebo	Placebo	Participants received dose and administration schedule (every 2 weeks or once a month) changes that simulated the changes for participants receiving darbepoetin alfa.

Primary Outcome Measures

Name	Time	Method
Time to All Cause Death or First Hospitalization for Worsening Heart Failure	From randomization to the end of study; maximum time on study was 73 months	Time to death from any cause or first hospital admission for worsening heart failure (adjudicated by the Clinical Endpoint Committee), whichever occurred first, estimated by Kaplan-Meier method. Participants not experiencing a qualifying event during the study were censored at their last contact time or the study termination date, whichever occurred first.

Secondary Outcome Measures

Name	Time	Method
Time to Cardiovascular Death or First Hospital Admission for Worsening Heart Failure	From randomization to the end of study; maximum time on study was 73 months	Time to cardiovascular death or first hospital admission for worsening heart failure, whichever occured first, estimated using the Kaplan Meier method. Participants not experiencing a qualifying event during the study were censored at their last contact time or the study termination date, whichever occurred first.
Time to Death From Any Cause	From randomization to the end of study; maximum time on study was 73 months	Time from randomization to death due to any cause, estimated by the Kaplan-Meier method. Participants not experiencing a qualifying event during the study were censored at their last contact time or the study termination date, whichever occurred first.
Change From Baseline to Month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score	Baseline and Month 6	The KCCQ is a disease-specific patient-reported outcomes measure for patients with heart failure. It consists of 23 items, is comprised of 7 clinically relevant scales (Symptom Frequency, Symptom Burden, Symptom Stability, Physical Limitation, Social Limitation, Quality of Life, and Self-Efficacy), and yields 3 summary scores (Clinical Summary, Total Symptom, and Overall Summary Scores). Scale and summary scores range between 0 and 100, with higher scores indicating better health status (eg, better functioning, fewer symptoms, better quality of life). Least squares means were calculated from a mixed effects model estimating treatment effect adjusted for region, type of device, and Baseline KCCQ score.
Change From Baseline to Month 6 in KCCQ Symptom Frequency Score	Baseline and Month 6	The KCCQ is a disease-specific patient-reported outcomes measure for patients with heart failure. It consists of 23 items, is comprised of 7 clinically relevant scales (Symptom Frequency, Symptom Burden, Symptom Stability, Physical Limitation, Social Limitation, Quality of Life, and Self-Efficacy), and yields 3 summary scores (Clinical Summary, Total Symptom, and Overall Summary Scores). Scale and summary scores range between 0 and 100, with higher scores indicating better health status (eg, better functioning, fewer symptoms, better quality of life). Least squares means were calculated from a mixed effects model estimating treatment effect adjusted for region, type of device, and Baseline KCCQ score.