Trial to Reduce Cardiovascular Events With Aranesp® Therapy (TREAT)

Study Overview
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Brief Summary
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The purpose of this study is to assess the impact of treatment of anemia with darbepoetin alfa to a hemoglobin target of 13 g/dL on (1) all-cause mortality and nonfatal cardiovascular events, and (2) progression to end-stage renal disease or death, in subjects with chronic kidney disease and type 2 diabetes mellitus. Academic PI/Executive Committee Chairman: Marc Pfeffer, MD, PhD

Official Title
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Trial to Reduce Cardiovascular Events With Aranesp® Therapy

Conditions
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Kidney Disease, Diabetes Mellitus, Anemia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hemoglobin less than or equal to 11 g/dL History of Chronic Kidney Disease eGFR (estimated glomerular filtration rate) greater than or equal to 20 mL/min/1.73 m2 and less than or equal to 60 mL/min/1.73 m2 Tsat (transferrin saturation) greater than 15% Exclusion Criteria: Uncontrolled hypertension Erythropoietic protein use within 12 weeks of randomization

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 |
| --- | --- |
| Active Comparator: Active<br> | Drug: darbepoetin alfa<br>* Starting dose : 0.75 mcg/kg subcutaneous (SC) every two weeks (Q2W); subsequent doses titrated to achieve hemoglobin (Hb) target of 13.0 g/dL<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Volume and dose frequency changes resembling dosing in the active treatment group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to All-cause Mortality or Cardiovascular (CV) Events Including Hospitalization Due to Acute Myocardial Ischemia, Congestive Heart Failure (CHF), Myocardial Infarction (MI), and Cerebrovascular Accident (CVA) | Time from randomization to the first confirmed composite event. Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized. | Until a primary cardiovascular event (death, myocardial ischemia, congestive heart failure, myocardial infarction or cerebrovascular accident) occurred or 28 March 2009, whichever occurred first | 
| Time to All-cause Mortality or End Stage Renal Disease (ESRD) | Time from randomization to first event of all-cause mortality or ESRD. Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized. | Until a primary cardiovascular event (death, myocardial ischemia, congestive heart failure, myocardial infarction or cerebrovascular accident) occurred or 28 March 2009, whichever occurred first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to All-cause Mortality | Time from randomization to all-cause mortality. Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized. | Until a primary cardiovascular event (death, myocardial ischemia, congestive heart failure, myocardial infarction or cerebrovascular accident) occurred or 28 March 2009, whichever occurred first | 
| Time to Cardiovascular Mortality | Time from randomization to cardiovascular (CV) mortality. Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized. | Until a primary cardiovascular event (death, myocardial ischemia, congestive heart failure, myocardial infarction or cerebrovascular accident) occurred or 28 March 2009, whichever occurred first | 
| Time to Myocardial Infarction | Time from randomization to fatal or non-fatal myocardial infarction (MI). Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized. | Until a primary cardiovascular event (death, myocardial ischemia, congestive heart failure, myocardial infarction or cerebrovascular accident) occurred or 28 March 2009, whichever occurred first | 
| Time to Cerebrovascular Accident | Time from randomization to fatal or non-fatal cerebrovascular accident (CVA). Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized. | Until a primary cardiovascular event (death, myocardial ischemia, congestive heart failure, myocardial infarction or cerebrovascular accident) occurred or 28 March 2009, whichever occurred first | 
| Time to Congestive Heart Failure | Time from randomization to fatal or non-fatal congestive heart failure(CHF). Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized. | Until a primary cardiovascular event (death, myocardial ischemia, congestive heart failure, myocardial infarction or cerebrovascular accident) occurred or 28 March 2009, whichever occurred first | 
| Time to End Stage Renal Disease | Time from randomization to end stage renal disease (ESRD). Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized. | Until a primary cardiovascular event (death, myocardial ischemia, congestive heart failure, myocardial infarction or cerebrovascular accident) occurred or 28 March 2009, whichever occurred first | 
| Rate of Decline in Estimated Glomerular Filtration Rate (eGFR) Relative to Baseline | GFR was estimated using the following MDRD formula: 186 x [Serum creatinine]^(-1.154) x [Age]^(-0.203) x [0.742 if subject is female] x [1.210 if subject is black]. Change from baseline in eGFR at week 49 for each treatment group are presented. The treatment effect of the rate of decline in eGFR per year was estimated using the mixed model. | Until a primary cardiovascular event (death, myocardial ischemia, congestive heart failure, myocardial infarction or cerebrovascular accident) occurred or 28 March 2009, whichever occurred first | 
| Change in Patient Reported Fatigue Relative to Baseline at Week 25 | Change in patient reported fatigue measured by the Functional Assessment of Cancer Therapy (FACT) - Fatigue scale from baseline to week 25. Range and direction of scale: 0 = most fatigue; 52 = least fatigue | Baseline and week 25 | 
| Time to Hospitalization Due to Acute Myocardial Ischemia | Time from randomization to hospitalization due to acute myocardial ischemia. Kaplan-Meier estimate of the median time was not estimable due to low proportion of participants experiencing at least one events, therefore participants experiencing at least one event were summarized. | Until a primary cardiovascular event (death, myocardial ischemia, congestive heart failure, myocardial infarction or cerebrovascular accident) occurred or 28 March 2009, whichever occurred first |