Overview

This trial is active, not recruiting.

Conditions chronic kidney disease, diabetes
Treatment darbepoetin alfa
Phase phase 3
Sponsor Translational Research Informatics Center, Kobe, Hyogo, Japan
Collaborator Showa University School of Medicine
Start date December 2011
End date June 2017
Trial size 476 participants
Trial identifier NCT01581073, TRIGU1115, UMIN000006616

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
darbepoetin alfa
Darbepoetin alfa is used for targeting Hb level of 11-13g/dL in high Hb group, and 9-11g/dL in low Hb group.
(Active Comparator)
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.
darbepoetin alfa
Darbepoetin alfa is used for targeting Hb level of 11-13g/dL in high Hb group, and 9-11g/dL in low Hb group.

Primary Outcomes

Measure
Composite renal outcome of chronic dialysis, kidney transplantation, eGFR 6 mL/min/1.73m2 or less, or eGFR less than 50% of initial value.
time frame: 96 weeks

Secondary Outcomes

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

Eligibility Criteria

Male or female participants from 20 years up to 85 years old.

Inclusion Criteria: 1. CKD patients who have not received chronic dialysis 2. eGFR 8 and more and less than 20 mL/min/1.73m2 determined twice in last 12 weeks. 3. CKD patients with renal anemia at Hb less than 10g/dL within last 8 weeks 4. CKD patients with TSAT 20% and higher or serum ferritin 100ng/mL and higher. 5. CKD patients treated with standard care 6. CKD patients provided written informed consent. Exclusion Criteria: 1. Diabetes (treated, or HbA1c 6.4% IFCC) 2. CKD patients treated with ESA other than epoetins and darbepoetin. 3. CKD patients treated with epoetin 24000 IU/4w or more. 4. CKD patients treated with darbepoetin 90μg/4w or more. 5. Uncontrolled hypertension (180/10mmHg and higher) 6. Heart failure (NYHA III and IV) 7. malignancy, hematological disorder 8. malnutrition 9. Active and continuous gastrointestinal tract bleeding 10. ANCA associated glomerulonephritis, acute infection, active SLE 11. CKD patients who will undergo dialysis or receive transplantation within 6 months 12. Myocardial infarction within last 6 months 13. Stroke or pulmonary embolism within last 12 months 14. Severe allergy 15. Pregnant women, women on lactation, or CKD patients who plant to get pregnant 16. Allergy against erythropoetin 17. Ineligible patients according to the investigator's judgment

Additional Information

Official title Prevention of End Stage Kidney Disease by Darbepoetin Alfa In CKD Patients With Non-diabetic Kidney Disease
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Translational Research Informatics Center, Kobe, Hyogo, Japan.