A Proof-of-Concept Study of Darbepoetin Alfa in Partial Correction of Anemia in Chinese With Diabetic Nephropathy

The Chinese University of Hong Kong

Status

Terminated

Conditions

Anemia

Chronic Kidney Disease

Diabetes Mellitus

Treatments

Drug: Darbepoetin alfa

Study type

Interventional

Funder types

Other

Identifiers

NCT00907608

PWH-2008-darbe

Details and patient eligibility

About

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.

Full description

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.

Enrollment

16 patients

Sex

All

Ages

20+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female patients aged above 20 years old
Patients with Type 1 or Type 2 diabetes mellitus
Estimated glomerular filtration rate less than 59 mL/min/1.73m2
Patients not on renal replacement therapy
Hemoglobin level at baseline : women less than 9.5 g/dL (inclusive) and men less than 10.5 g/dL (inclusive)
All patients should be on a stable dose of the following medications 4 weeks before enrolment :
Aspirin 80mg daily unless contraindicated
Statin to achieve stable and optimal LDL-cholesterol level
Maximal tolerated dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
Anti-hypertensive treatment to maintain blood pressure target of less than 130/80 mmHg or a level achieved without undue side effects
Oral anti-diabetic drugs or insulin to maintain HbA1C less than 9.5%

Exclusion criteria

Pregnancy, breast feeding or patient has plans of becoming pregnant during the study period
Known non-diabetic renal disease
Known cause of anemia not related to chronic kidney disease
Presence of hemoglobinopathy
History of pure red cell aplasia
Known allergy to Darbepoetin alfa
Severe liver impairment (>= 3x ULN of ALT)
Poorly controlled hypertension, systolic BP >= 160mmHg or diastolic BP >= 100mmHg
Significant cardiovascular disease within 3 months of enrolment including acute coronary syndrome, cardiac revascularization procedure, transient ischemic attack and cerebrovascular accident
History of major gastrointestinal bleeding in the 5 years prior to consent
Investigational drugs within 30 days of enrolment
Any other medical conditions that is considered as unsuitable for the study by investigator