Clinical trial NCT01581073: PRevention of End Stage Kidney Disease by Darbepoetin Alfa In Chronic Kidney Disease Patients With nondiabeTic Kidney Disease
Official title: Prevention of End Stage Kidney Disease by Darbepoetin Alfa In CKD Patients With Non-diabetic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease
Diabetes
Keywords: renal anemia
erythropoiesis stimulating agent
hemoglobin
non-diabetes
CKD
Chronic Kidney Disease patients without diabetes
Lead sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Sponsor class: OTHER
Collaborators: name: Showa University School of Medicine
First posted: 2012-04-19
Enrollment: 476
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
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 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: 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.

Eligibility criteria: 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

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.
timeFrame: 96 weeks
Secondary outcomes:
measure: Composite cardiovascular outcome of cardiovascular death, stroke, myocardial infarction, leg amputation, admission by heart failure or angina.
timeFrame: 96 weeks
measure: Time from enrollment to initiation of dialysis
timeFrame: 96 weeks
measure: Time from enrollment to 50% reduction of eGFR from initial value
timeFrame: 96 weeks
measure: Time from enrollment to death by any cause
timeFrame: 96 weeks
measure: Change of eGFR from enrollment
timeFrame: 96 weeks
measure: Change of proteinuria/Cr ratio
timeFrame: 96 weeks
measure: Renal protection in patients who maintained the target Hb more than half the time
timeFrame: 96 weeks
measure: 50% renal survival
timeFrame: 96 weeks
measure: Stroke
timeFrame: 96 weeks
measure: Myocardial infarction
timeFrame: 96 weeks
measure: Development of malignancy
timeFrame: 96 weeks
measure: Number of Participants with Adverse Events baseline
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Shinagawa
country: Japan
facility: Showa University School of Medicine
state: Tokyo
Study officials:
References:
citation: Hayashi T, Maruyama S, Nangaku M, Narita I, Hirakata H, Tanabe K, Morita S, Tsubakihara Y, Imai E, Akizawa T; PREDICT Investigators. Darbepoetin Alfa in Patients with Advanced CKD without Diabetes: Randomized, Controlled Trial. Clin J Am Soc Nephrol. 2020 May 7;15(5):608-615. doi: 10.2215/CJN.08900719. Epub 2020 Apr 3.
citation: Imai E, Maruyama S, Nangaku M, Hirakata H, Hayashi T, Narita I, Kono H, Nakatani E, Morita S, Tsubakihara Y, Akizawa T. Rationale and study design of a randomized controlled trial to assess the effects of maintaining hemoglobin levels using darbepoetin alfa on prevention of development of end-stage kidney disease in non-diabetic CKD patients (PREDICT Trial). Clin Exp Nephrol. 2016 Feb;20(1):71-6. doi: 10.1007/s10157-015-1133-z. Epub 2015 Jun 17.