Clinical trial NCT00907608: A Proof-of-Concept Study of Darbepoetin Alfa in Partial Correction of Anemia in Chinese With Diabetic Nephropathy
Official title: A Proof-of-Concept Study of Darbepoetin Alfa in Partial Correction of Anemia in Chinese With Diabetic Nephropathy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diabetes Mellitus
Chronic Kidney Disease
Anemia
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2009-05-22
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite cardiovascular endpoint of myocardial infarction, congestive heart failure, arrhythmia, stroke, transient ischemic attack, amputation or ulceration / necrosis of lower limb
timeFrame: 3 years
measure: Death
timeFrame: 3 years
Secondary outcomes:
measure: Doubling of mean serum creatinine
timeFrame: 3 years
measure: 50% reduction in mean estimated glomerular filtration rate during baseline period as estimated by the abbreviated Modification of Diet in Renal Disease equation
timeFrame: 3 years
measure: Estimated glomerular filtration rate less than 15 mL/min/1.73m-2
timeFrame: 3 years
measure: Change in fasting urinary albumin creatinine ratio
timeFrame: 3 years
measure: Need for dialysis
timeFrame: 3 years
measure: Number of hospital admissions, total number of days of hospital stay and attendance at the Accident and Emergency Department
timeFrame: 3 years
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Prince of Wales Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Peter CY Tong, MBChB
role: PRINCIPAL_INVESTIGATOR
References: