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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Darbepoetin Alfa Treatment on Mortality and Morbidity in Heart Failure (HF) Subjects With Symptomatic Left Ventricular Systolic Dysfunction and Anemia

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

Intervention / Treatment
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* Drug: Darbepoetin alfa
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darbepoetin alfa<br>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. | Drug: Darbepoetin alfa<br>* Administered by subcutaneous injection<br>* Other names: Aranesp®;|
| Placebo Comparator: Placebo<br>Participants received dose and administration schedule (every 2 weeks or once a month) changes that simulated the changes for participants receiving darbepoetin alfa. | Drug: Placebo<br>* Placebo subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to All Cause Death or First Hospitalization for Worsening Heart Failure | 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. | From randomization to the end of study; maximum time on study was 73 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Death From Any Cause | 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. | 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 | 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. | From randomization to the end of study; maximum time on study was 73 months | 
| Change From Baseline to Month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | 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. | Baseline and Month 6 | 
| Change From Baseline to Month 6 in KCCQ Symptom Frequency Score | 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. | Baseline and Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Survival study, morbidity and mortality, heart failure hospitalization, all-cause death, patient-reported outcomes, Kansas City Cardiomyopathy questionnaire, anemia treatment