A Proof-of-Concept Study of Darbepoetin Alfa in Partial Correction of Anemia in Chinese With Diabetic Nephropathy
The purpose of this study is to examine the effect of partial correction of anemia with Darbepoetin alfa to a target of 11 g.dL (female) or 12 g/dL (male) on the reduction of cardiovascular morbidity and total mortality.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Proof-of-Concept Study of Darbepoetin Alfa in Partial Correction of Anemia in Chinese With Diabetic Nephropathy|
- Composite cardiovascular endpoint of myocardial infarction, congestive heart failure, arrhythmia, stroke, transient ischemic attack, amputation or ulceration / necrosis of lower limb [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Death [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Doubling of mean serum creatinine [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- 50% reduction in mean estimated glomerular filtration rate during baseline period as estimated by the abbreviated Modification of Diet in Renal Disease equation [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Estimated glomerular filtration rate less than 15 mL/min/1.73m-2 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Change in fasting urinary albumin creatinine ratio [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Need for dialysis [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Number of hospital admissions, total number of days of hospital stay and attendance at the Accident and Emergency Department [ Time Frame: 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||December 2007|
|Study Completion Date:||May 2009|
|Primary Completion Date:||May 2009 (Final data collection date for primary outcome measure)|
Receive Darbepoetin alfa
Drug: Darbepoetin alfa
Starting dose of 20 microgram per week, to be titrated over a 3-month period until target hemoglobin level is reached (female: 11 g/dL and male: 12 g/dL). Route of administration is subcutaneous injection.
|No Intervention: 2|
Diabetes is the leading cause of end stage renal disease and cardiovascular disease with 60 percent of the global diabetic population coming from Asia. Growing evidence confirms the predictive role of chronic kidney disease (CKD) on cardiovascular morbidity and mortality. This is due to the constellation of conventional and non-conventional risk factors in patients who develop CKD, such as anemia, inflammation and abnormal bone metabolism. In this regard, anemia is a risk factor for cardiovascular disease and all-cause mortality in patients with CKD, patients with left ventricular dysfunction and in general population.
Effective erythropoiesis is dependent on the production of erythropoietin by the kidneys. Anemia is a common finding in patients with diabetes and up to 20% of diabetic patients are noted to have anemia. In a meta-analysis of community-based population studies, anemia interacts with CKD to increase the risk of coronary heart disease, stroke and all-cause mortality among patients with diabetes. Previous studies that examined the effect of erythropoietin therapy on anemic subjects with CKD did not find statistical difference in mortality rates between the treated and untreated groups. Possible explanations for the lack of benefits include higher level of blood pressure and increased blood viscosity leading to worsening of chronic congestive heart failure in the treated subjects. We hypothesize that partial correction of hemoglobin may be more appropriate.