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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00358215
First received: July 27, 2006
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Heart Failure
Anemia
Cardiovascular Disease
Ventricular Dysfunction
Congestive Heart Failure
Drug: Darbepoetin alfa
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Time to All Cause Death or First Hospitalization for Worsening Heart Failure [ Time Frame: From randomization to the end of study; maximum time on study was 73 months ] [ Designated as safety issue: No ]
    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:
  • Time to Death From Any Cause [ Time Frame: From randomization to the end of study; maximum time on study was 73 months ] [ Designated as safety issue: Yes ]
    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.

  • Time to Cardiovascular Death or First Hospital Admission for Worsening Heart Failure [ Time Frame: From randomization to the end of study; maximum time on study was 73 months ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline to Month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    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.


Enrollment: 2278
Study Start Date: June 2006
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Darbepoetin alfa
Administered by subcutaneous injection
Other Name: Aranesp®
Placebo Comparator: Placebo
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
Placebo subcutaneous injection

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00358215

  Show 755 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00358215     History of Changes
Other Study ID Numbers: 20050222, RED-HF™ Trial
Study First Received: July 27, 2006
Results First Received: October 23, 2013
Last Updated: July 14, 2014
Health Authority: Argentina: ANMAT (Administracion Nacional de Medicamentos Alimentos y Tecnologia Medica)
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: AGES - PharmaMed Austria Institut Wissenschaft & Information
Belgium: Federal Public Service
Brazil: ANVISA (Agência Nacional de Vigilância Sanitária)
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ministry of Health
Canada: Health Canada
Chile: Health Ministry
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Estonia: State Agency of Medicines
Finland: Lääkelaitos
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Hungary: National Institute of Pharmacy
India: Central Drugs Standard Control Organization
Ireland: Irish Medicines Board (IMB)
Israel: Ministry of Health
Italy: Local Ethics Committees
Latvia: State Agency of Medicines
Lithuania: State Medicines Control Agency of Lithuania
Mexico: Ministry of Health
Netherlands: CCMO (Centrale Commissie Mensgebonden Onderzoek): Central Committee Human Bound Research
Norway: Norwegian Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: Instituto Nacional da Farmácia e do Medicamento (INFARMED)
Romania: Romanian National Drug Agency
Russia: Ministry of Health
Slovakia: Štátny ústav pre kontrolu lieciv
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Switzerland: Swissmedic (Swiss Agency for Therapeutic Products)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Ukraine: Ministry of Health

Keywords provided by Amgen:
Survival study
morbidity and mortality
heart failure hospitalization
all-cause death
patient-reported outcomes
Kansas City Cardiomyopathy questionnaire
anemia treatment

Additional relevant MeSH terms:
Anemia
Cardiovascular Diseases
Heart Failure
Ventricular Dysfunction
Hematologic Diseases
Heart Diseases
Darbepoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014