Renal Anemia Treatment with Roxadustat for Non-dialysis Patients with Lower Extremity Artery Disease: The REFINE trial

JRCT ID: jRCTs031230506

Registered date:12/12/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: lower extremities artery disease, renal anemia
• Date of first enrollment: 25/04/2024
• Target sample size: 100
• Study type: Interventional
• Intervention(s): Intake of Roxadustat

Outcome(s)

• Primary Outcome: Change in hemoglobin level between baseline and 24 weeks after randomization

Secondary Outcome

Changes in laboratory tests , ABI, duplex ultrasound (PSV, PSVR), QOL score (EQ-5D-5L, SF-36v2, PHQ-9, Vascu-QOL, WIQ), 6 minutes walking distance between baseline and 24 weeks.
Clinical outcomes at 24 weeks (all-cause death, cardiovascular death, non-cardiovascular death, myocardial infarction, unplanned coronary revascularization, unplanned peripheral revascularization, stroke, admission due to heart failure, bleeding, lower limb amputation, hemodialysis)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 90age old
• Gender: Both

Include criteria

1.Aged 20-90 years at the time of randomization.
2.Established LEAD, defined as ABI <0.90 or history of lower extremity peripheral artery revascularization within the pre-treatment observation period.
3.eGFR less than 60ml/min/1.73m2 within the pre-treatment observation period.
4.Hemoglobin level of more than or equal to 7.5 and less than 11.0 g/dl at the time of randomization.
5.TSAT more than or equal to 20% at the time of randomization.
6.Folic acid and vitamin B12 levels above the lower limit of normal within the pre-treatment observation period.
7.Provided written consent to participate in the study.

Exclude criteria

1.Hemodialysis or peritoneal dialysis at the time of randomization, or scheduled within 6 months from the time of randomization
2.History of polycystic kidney disease
3.Treated with an ESA within 5 weeks before randomization
4.Red blood cell transfusion within 12 weeks before randomization, or expected to occur during the study period
5.A history of treatment with HIF-PH inhibitors within 3 months before randomization
6.Anemia due to conditions other than chronic kidney disease
7.Patients with major bleeding* within 3 months before randomization (*major bleeding is defined as BARC 3 bleeding)
8.Known history of myelodysplastic syndrome, multiple myeloma, hereditary hematologic disease such as thalassemia, sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than CKD, hemosiderosis, hemochromatosis, known coagulation disorder, or hypercoagulable condition
9.Presence of a malignant tumor noted within 2 years before randomization, except for treated basal cell carcinoma of the skin, squamous cell carcinoma cured by resection, and intraepithelial carcinoma of the cervix
10.Diabetic retinopathy on treatment, or untreated pre-proliferative/proliferative diabetic retinopathy by Davis classification
11.History of acute myocardial infarction, cerebral infarction, deep vein thrombosis, or pulmonary thromboembolism within 1 year before randomization
12.History of pulmonary hypertension
13.Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV Ab)
14.Any clinically significant infection or evidence of an active underlying infection
15.Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis)
16.Any prior functioning organ transplant or a scheduled organ transplantation, or anephric
17.AST or ALT >3 times the upper limit of normal, total bilirubin >2 times the upper limit of normal, or Child-Pugh B or C within the pre-treatment observation period
18.Poorly controlled arterial hypertention (defined as SBP >180mmHg) within the pre-treatment observation period
19.Judged by the principal investigator to be inappropriate as a research subject

Related Information

• Primary Sponsor: Ueki Yasushi
• Source(s) of Monetary Support: Astellas Pharma Inc.