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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
Results First Received: October 23, 2013  
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
Conditions: Heart Failure
Anemia
Cardiovascular Disease
Ventricular Dysfunction
Congestive Heart Failure
Interventions: Drug: Darbepoetin alfa
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First patient enrolled 13 June 2006; Last patient enrolled 4 May 2012

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo Participants received dose and administration schedule (every 2 weeks or once a month) changes that simulated the changes for participants receiving 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.

Participant Flow:   Overall Study
    Placebo   Darbepoetin Alfa
STARTED   1142   1136 
Received Investigational Product   1140   1133 
COMPLETED   463 [1]   484 [1] 
NOT COMPLETED   679   652 
Ineligibility determined                4                3 
Adverse Event                83                65 
Withdrawal by Subject                111                102 
Participant request                65                64 
Physician Decision                47                39 
Lost to Follow-up                16                22 
Death                265                281 
Protocol Violation                64                59 
Pregnancy                1                0 
Other                21                14 
Did not receive investigational product                2                3 
[1] Participants who completed investigational product



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Participants received dose and administration schedule (every 2 weeks or once a month) changes that simulated the changes for participants receiving 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.
Total Total of all reporting groups

Baseline Measures
   Placebo   Darbepoetin Alfa   Total 
Overall Participants Analyzed 
[Units: Participants]
 1142   1136   2278 
Age 
[Units: Years]
Mean (Standard Deviation)
 69.6  (11.3)   70.0  (11.6)   69.8  (11.4) 
Gender 
[Units: Participants]
     
Female   486   458   944 
Male   656   678   1334 
Race/Ethnicity, Customized 
[Units: Participants]
     
White or Caucasian   768   781   1549 
Black or African American   113   89   202 
Hispanic or Latino   84   98   182 
Asian   162   162   324 
Japanese   0   1   1 
American Indian or Alaska Native   2   2   4 
Native Hawaiian or Other Pacific Islander   1   0   1 
Other   12   3   15 
Region 
[Units: Participants]
     
North America   323   321   644 
Latin America and Asia   286   285   571 
Western Europe, Israel, South Africa, Australia   306   303   609 
Eastern Europe and Russia   227   227   454 
Device Usage [1] 
[Units: Participants]
     
CRT with or without ICD   143   143   286 
ICD without CRT   124   122   246 
None   875   871   1746 
[1] Usage of implantable cardioverter defibrillator / cardiac resynchronization therapy (ICD/CRT)
Kansas City Cardiomyopathy Questionnaire: Overall Summary Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 56.5  (22.5)   55.8  (22.6)   56.2  (22.5) 
[1] The KCCQ is a patient-reported measure for patients with heart failure. It consists of 23 items, is comprised of 7 clinically relevant scales (Symptom Frequency, Burden and Stability, Physical and Social Limitation, Quality of Life, and Self-Efficacy), and yields 3 summary scores (Clinical Summary, Total Symptom, and Overall Summary Scores). Scores range between 0 and 100, with higher scores indicating better health status (eg, better functioning, quality of life, fewer symptoms). Number of participants with available data = 1106 and 1104 for each treatment group respectively, total = 2210.
Study Specific Characteristic [Kansas City Cardiomyopathy Questionnaire: Symptom Frequency Scale [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 63.3  (25.2)   63.1  (25.6)   63.2  (25.4) 
[1] The KCCQ is a patient-reported measure for patients with heart failure. It consists of 23 items, is comprised of 7 clinically relevant scales (Symptom Frequency, Burden and Stability, Physical and Social Limitation, Quality of Life, and Self-Efficacy), and yields 3 summary scores (Clinical Summary, Total Symptom, and Overall Summary Scores). Scores range between 0 and 100, with higher scores indicating better health status (eg, better functioning, quality of life, fewer symptoms). Number of participants with available data = 1106 and 1104 for each treatment group respectively, total = 2210.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Secondary:   Time to Death From Any Cause   [ Time Frame: From randomization to the end of study; maximum time on study was 73 months ]

3.  Secondary:   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 ]

4.  Secondary:   Change From Baseline to Month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score   [ Time Frame: Baseline and Month 6 ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Change From Baseline to Month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Measure Description 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.
Time Frame Baseline and Month 6  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat participants with non-missing change from Baseline to Month 6 in KCCQ score.

Reporting Groups
  Description
Placebo Participants received dose and administration schedule (every 2 weeks or once a month) changes that simulated the changes for participants receiving 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.

Measured Values
   Placebo   Darbepoetin Alfa 
Participants Analyzed 
[Units: Participants]
 929   928 
Change From Baseline to Month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 4.48  (0.68)   6.68  (0.68) 


Statistical Analysis 1 for Change From Baseline to Month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.005
Least Squares Mean Difference [4] 2.20
Standard Error of the mean (0.79)
95% Confidence Interval 0.65 to 3.75
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Mixed effects model estimating treatment effect adjusted for region, type of device, and Baseline KCCQ score.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



5.  Secondary:   Change From Baseline to Month 6 in KCCQ Symptom Frequency Score   [ Time Frame: Baseline and Month 6 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


Publications:
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