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

This study has been terminated.
(Due to difficulty in patient recruitment)
Sponsor:
Information provided by:
Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT00907608
First received: May 21, 2009
Last updated: NA
Last verified: May 2009
History: No changes posted
  Purpose

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.


Condition Intervention
Diabetes Mellitus
Chronic Kidney Disease
Anemia
Drug: Darbepoetin alfa

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 16
Study Start Date: December 2007
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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

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

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00907608

Locations
China
Prince of Wales Hospital
Hong Kong, China
Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
Principal Investigator: Peter CY Tong, MBChB Chinese University of Hong Kong
  More Information

No publications provided

Responsible Party: Dr Peter CY Tong, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT00907608     History of Changes
Other Study ID Numbers: PWH-2008-darbe
Study First Received: May 21, 2009
Last Updated: May 21, 2009
Health Authority: Hong Kong: Department of Health

Additional relevant MeSH terms:
Diabetes Mellitus
Anemia
Kidney Diseases
Renal Insufficiency, Chronic
Diabetic Nephropathies
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hematologic Diseases
Urologic Diseases
Renal Insufficiency
Diabetes Complications
Darbepoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014