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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
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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 ]

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
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Time Frame Informed consent to 30 days post treatment. Max time 72 months
Additional Description The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Frequency Threshold
Threshold above which other adverse events are reported   5  

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.

Other Adverse Events
    Placebo   Darbepoetin Alfa
Total, other (not including serious) adverse events     
# participants affected / at risk   741/1140 (65.00%)   710/1133 (62.67%) 
Cardiac disorders     
Angina pectoris † 1     
# participants affected / at risk   60/1140 (5.26%)   52/1133 (4.59%) 
Cardiac failure † 1     
# participants affected / at risk   92/1140 (8.07%)   69/1133 (6.09%) 
Gastrointestinal disorders     
Constipation † 1     
# participants affected / at risk   68/1140 (5.96%)   81/1133 (7.15%) 
Diarrhoea † 1     
# participants affected / at risk   135/1140 (11.84%)   148/1133 (13.06%) 
Nausea † 1     
# participants affected / at risk   75/1140 (6.58%)   71/1133 (6.27%) 
General disorders     
Asthenia † 1     
# participants affected / at risk   112/1140 (9.82%)   88/1133 (7.77%) 
Fatigue † 1     
# participants affected / at risk   84/1140 (7.37%)   86/1133 (7.59%) 
Oedema peripheral † 1     
# participants affected / at risk   118/1140 (10.35%)   115/1133 (10.15%) 
Infections and infestations     
Bronchitis † 1     
# participants affected / at risk   88/1140 (7.72%)   99/1133 (8.74%) 
Influenza † 1     
# participants affected / at risk   71/1140 (6.23%)   61/1133 (5.38%) 
Nasopharyngitis † 1     
# participants affected / at risk   111/1140 (9.74%)   117/1133 (10.33%) 
Upper respiratory tract infection † 1     
# participants affected / at risk   73/1140 (6.40%)   95/1133 (8.38%) 
Urinary tract infection † 1     
# participants affected / at risk   71/1140 (6.23%)   82/1133 (7.24%) 
Injury, poisoning and procedural complications     
Fall † 1     
# participants affected / at risk   68/1140 (5.96%)   80/1133 (7.06%) 
Metabolism and nutrition disorders     
Gout † 1     
# participants affected / at risk   75/1140 (6.58%)   71/1133 (6.27%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1     
# participants affected / at risk   78/1140 (6.84%)   101/1133 (8.91%) 
Back pain † 1     
# participants affected / at risk   87/1140 (7.63%)   93/1133 (8.21%) 
Pain in extremity † 1     
# participants affected / at risk   93/1140 (8.16%)   94/1133 (8.30%) 
Nervous system disorders     
Dizziness † 1     
# participants affected / at risk   143/1140 (12.54%)   138/1133 (12.18%) 
Headache † 1     
# participants affected / at risk   69/1140 (6.05%)   67/1133 (5.91%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1     
# participants affected / at risk   132/1140 (11.58%)   126/1133 (11.12%) 
Dyspnoea † 1     
# participants affected / at risk   174/1140 (15.26%)   157/1133 (13.86%) 
Vascular disorders     
Hypotension † 1     
# participants affected / at risk   83/1140 (7.28%)   73/1133 (6.44%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 15.1



  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
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