PRevention of End Stage Kidney Disease by Darbepoetin Alfa In Chronic Kidney Disease Patients With nondiabeTic Kidney Disease

Study Overview
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Brief Summary
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The purpose of this study is to ask whether treating non-diabetic chronic kidney disease (CKD) patients with GFR 8-20mL/min/1.73m2 by darbepoetin Alfa targeting Hb between 11.0 and 13.0g/dL preserves renal function better than targeting Hb between 9.0 and11.0g/dL. The investigators also ask whether the higher Hb targeting 11 to 13g/dL will not cause higher adverse events regarding cardiovascular diseases compared with lower Hb targeting 9 to 11g/dL.

Detailed Description
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Anemia is common among patients with chronic kidney disease (CKD) and is associated with an increased risk of cardiovascular and renal events. Although erythropoiesis stimulating agent (ESA) has been used to correct anemia, use of ESA (hemoglobin level at approximately 13 g/dL) did not reduce cardiovascular or renal events in diabetic CKD patients. Subgroup analysis of a recent randomized study suggested that use of darbepoetin alfa targeting Hb between 11 and 13 g/dL may preserve renal function better than targeting Hb between 9 and 11g/dL in non-diabetic CKD patients.

Official Title
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Prevention of End Stage Kidney Disease by Darbepoetin Alfa In CKD Patients With Non-diabetic Kidney Disease

Conditions
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Chronic Kidney Disease, Diabetes

Intervention / Treatment
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* Drug: Darbepoetin alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CKD patients who have not received chronic dialysis eGFR 8 and more and less than 20 mL/min/1.73m2 determined twice in last 12 weeks. CKD patients with renal anemia at Hb less than 10g/dL within last 8 weeks CKD patients with TSAT 20% and higher or serum ferritin 100ng/mL and higher. CKD patients treated with standard care CKD patients provided written informed consent. Exclusion Criteria: Diabetes (treated, or HbA1c 6.4% IFCC) CKD patients treated with ESA other than epoetins and darbepoetin. CKD patients treated with epoetin 24000 IU/4w or more. CKD patients treated with darbepoetin 90μg/4w or more. Uncontrolled hypertension (180/10mmHg and higher) Heart failure (NYHA III and IV) malignancy, hematological disorder malnutrition Active and continuous gastrointestinal tract bleeding ANCA associated glomerulonephritis, acute infection, active SLE CKD patients who will undergo dialysis or receive transplantation within 6 months Myocardial infarction within last 6 months Stroke or pulmonary embolism within last 12 months Severe allergy Pregnant women, women on lactation, or CKD patients who plant to get pregnant Allergy against erythropoetin Ineligible patients according to the investigator's judgment

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Hb group<br>Darbepoetin alfa is given to the patients. Target Hb level is 12.0g/dL and it should be maintained greater than or equal to 11.0g/dL and less than 13.0g/dL. If the patients do not have medical history of myocardial infarction, stroke, pulmonary embolism, unstable angina, or peripheral artery disease, the target Hb level will be greater than or equal to 12.0g/dL and less than 13.0g/dL. Maximum dose of darbepoetin alfa is 240 microgram per 4 weeks. | Drug: Darbepoetin alfa<br>* Darbepoetin alfa is used for targeting Hb level of 11-13g/dL in high Hb group, and 9-11g/dL in low Hb group.<br>|
| Active Comparator: Low Hb group<br>Darbepoetin alfa is given to the patients. Target Hb level is 10.0g/dL and it should be maintained greater than or equal to 9.0g/dL and less than 11.0g/dL. If the Hb level exceeds 10.0g/dL in patients, reduce the dose amount or stop giving dose. | Drug: Darbepoetin alfa<br>* Darbepoetin alfa is used for targeting Hb level of 11-13g/dL in high Hb group, and 9-11g/dL in low Hb group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite renal outcome of chronic dialysis, kidney transplantation, eGFR 6 mL/min/1.73m2 or less, or eGFR less than 50% of initial value. |  | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite cardiovascular outcome of cardiovascular death, stroke, myocardial infarction, leg amputation, admission by heart failure or angina. |  | 96 weeks | 
| Time from enrollment to initiation of dialysis |  | 96 weeks | 
| Time from enrollment to 50% reduction of eGFR from initial value |  | 96 weeks | 
| Time from enrollment to death by any cause |  | 96 weeks | 
| Change of eGFR from enrollment |  | 96 weeks | 
| Change of proteinuria/Cr ratio |  | 96 weeks | 
| Renal protection in patients who maintained the target Hb more than half the time |  | 96 weeks | 
| 50% renal survival |  | 96 weeks | 
| Stroke |  | 96 weeks | 
| Myocardial infarction |  | 96 weeks | 
| Development of malignancy |  | 96 weeks | 
| Number of Participants with Adverse Events baseline |  | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal anemia, erythropoiesis stimulating agent, hemoglobin, non-diabetes, CKD, Chronic Kidney Disease patients without diabetes