A Prospective, Open-label, Randomized, Multicenter Study on the Rational Hemoglobin Target Value in Patients With Anemia of Non-dialysis Chronic Kidney Disease Treated With Enarodustat
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,670
- 试验地点
- 1
- 主要终点
- Improvement of quality of life
研究概览
简要总结
The CANNON trial is a prospective, open-label, randomized, multicenter study designed to investigate rational hemoglobin target value in patients with anemia of non-dialysis chronic kidney disease treated with enarodustat. Eligible patients are randomly assigned 1:1 to the high-hemoglobin target group （hemoglobin of 13 g/dl）and low-hemoglobin target group （hemoglobin of 11 g/dl）and administered with enarodustat to achieve and maintain target hemoglobin over 96 weeks. The first primary endpoint was the difference of mean change in 36-Item Short Form Health Survey at week 24. The second primary endpoint was safety endpoints included time to major adverse cardiovascular + event (MACE+; all-cause mortality, myocardial infarction, stroke, and congestive heart failure requiring hospitalization) during 96 weeks.
详细描述
This study is a prospective, open-label, randomized controlled, multicenter investigation conducted among adult patients with ND-CKD anemia in China, with the aim of exploring the rational hemoglobin target value for the treatment of patients with ND-CKD anemia using enarodustat.
This study plans to enrol 1,670 patients with non-dialysis chronic kidney disease (ND-CKD) anemia. After screening, patients who meet the inclusion criteria and do not meet the exclusion criteria will be randomly assigned at a 1:1 ratio to: the low Hb target value group: with a Hb target value of 11 g/dL; the high Hb target value group: with a Hb target value of 13 g/dL. The initial dose of enarodustat tablets in both groups is 4 mg once daily. The dose will be adjusted in accordance with the instructions and the requirements of different Hb value groups.
The follow-up period will last for 96 weeks. The first primary endpoint was the difference of mean change in 36-Item Short Form Health Survey at week 24. The second primary endpoint was safety endpoints included time to major adverse cardiovascular + event (MACE+; all-cause mortality, myocardial infarction, stroke, and congestive heart failure requiring hospitalization) during 96 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-75 years at the time of consent to participate;
- •Body weight ranged from 45 to 100 kg;
- •Diagnosed with CKD stages 2-5 (10 ≤ eGFR < 90 mL/min/1.73m2) and were not dialysis dependent;
- •Diagnosed with renal anemia:
- •Hemoglobin level of 6 - 10 g/dL for those who have not received ESA or HIF-PHI treatment within 6 weeks at screening; 2)Hemoglobin level of 8 - 12 g/dL for those who are currently receiving ESA (ESA dosage ≤ 10,000 IU/week) or HIF-PHI (roxadustat dosage≤ 100 mg TIW) at screening;
- •Serum ferritin > 100 μg/L or transferrin saturation > 20% at screening;
- •Voluntary participation in the trial and signing of the informed consent form.
排除标准
- •Uncontrolled hypertension identified as systolic blood pressure >160mmHg or diastolic blood pressure >100mmHg after 4 weeks of regular and adequate drug therapy prior to screening;
- •Uncontrolled proteinuria identified as UACR >3000mg/g or 24-hour urine protein >3.5g in non-diabetic patients and UACR of >5000mg/g or 24-hour urine protein >5.5g in diabetic patients;
- •Anemia due to other reasons except CKD including systemic hematological disorders (such as myelodysplastic syndrome, aplastic anemia, etc.), hemolytic anemia, hemorrhagic anemia or cancer-related anemia;
- •History of autoimmune diseases which could result in anemia such as systemic lupus erythematosus and ANCA vasculitis;
- •History of active bleeding within 4 weeks prior to screening;
- •History of serious thrombotic event such as a myocardial infarction, cerebral infarction, pulmonary embolism, unstable angina, or PCI or cardiac surgery within 6 months prior to screening;
- •Severe heart failure (NYHA class IV) at screening;
- •History of blood transfusion within 2 months prior to screening;
- •History of usage of immunosuppressants or other immune therapies within 6 months prior to screening;
- •Patients who are estimated to require dialysis, kidney transplantation, or major surgery within 6 months;
- •Severe liver and biliary system complications (AST or ALT >3 times the upper limit of normal, total bilirubin >2 times the upper limit of normal) at screening;
- •Receiving ESA combined with roxadustat treatment at screening;
- •History of proliferative retinopathy or diabetic retinopathy requiring ophthalmological treatment;
- •Severe hyperparathyroidism (iPTH ≥ 500 pg/mL);
- •Severe active infections (such as active tuberculosis, fungal infections, etc.);
- •Patients who are bedridden or have difficulty walking, or have a history of atrial fibrillation or deep vein thrombosis of the lower limbs;
- •History of active tumors;
- •Female patients who are pregnant or breastfeeding, or non-childbearing women who do not agree to effective contraception;
- •Patients with a history of severe drug allergies (such as anaphylactic shock), or known allergies to any of the active ingredients or excipients of enarodostat;
- •Patients who are currently participating in any other interventional clinical trial;
- •Other reasons determined by the investigator not suitable for participation in the study.
研究组 & 干预措施
high-hemoglobin target group
Patients are managed to achieve and maintain hemoglobin target of 13 g/dl over 96 weeks.
干预措施: Enarodustat (Drug)
low-hemoglobin target group
Patients are managed to achieve and maintain hemoglobin target of 11 g/dl over 96 weeks.
干预措施: Enarodustat (Drug)
结局指标
主要结局
Improvement of quality of life
时间窗: At week 24
Mean change in 36-Item Short Form Health Survey
Effect on MACE+ events
时间窗: During 96 weeks
First occurence of major adverse cardiovascular + event (MACE+; all-cause mortality, myocardial infarction, stroke, and congestive heart failure requiring hospitalization) .
次要结局
- Effect on blood transfusions(During 96 weeks)
- Effect on eGFR(At weeks 24, 48, 72, and 96)
- Effect on thromboembolic events(During 96 weeks)
- Effect on MACE events(During 96 weeks)
- Effect on cardiovascular death(During 96 weeks)
- Effect on renal events(During 96 weeks)