Phase 4, Multicenter, Randomized, Open-Lable, Active-Controlled Study of the Efficacy and Safty of HIF-PHI for the Treatment of Anemia and Risks of Cardiovascular and Cerebrovascular Events in Incident-Dialysis Patients
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- The incidence of cardiovascular and cerebrovascular events within 52 weeks.
研究概览
简要总结
The purpose of the study is to determin whether HIF-PHI is safe and effective in the treatment of anemia and meanwhile reduces the risk of cardiovascular and cerebrovascular events in patients who have just initiated dialysis.
详细描述
There is a screening period of up to 2 weeks, a treatment period of a minimum of 52 weeks and a maximum of approximately up to 3 years after last patient is randomized. A total of up to 400 patients will be randomized in a 1:1 ratio to receive either open-lable HIF-PHI or Active Control (Epoetin alfa).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient or his/her legal guardian signs the informed consent
- •Age ≥18 years
- •Weight: 45-100 kg (included)
- •Patients with CKD end-stage renal disease received hemodialysis treatment ≤ 4 weeks, dialysis frequency was stable, kt / V ≥ 1.2, and planned to continue dialysis treatment during the study period
- •No iron deficiency.
- •No folate or Vitamin B12 deficiency.
- •No abnormal liver tests.
- •During the screening period, value of Hb is less than
排除标准
- •Evidence of any clinically significant infection or active potential infection;
- •Active hepatitis or any of the following abnormalities (ALT ≥ 2 times the upper limit of normal value, AST ≥ 2 times the upper limit of normal value, DBIL ≥ 2 times the upper limit of normal value);
- •Patients with severe cardiovascular disease have had myocardial infarction, coronary artery bypass or PCI operation within 3 months prior to participating in the study.
- •Patients have experienced severe cerebrovascular diseases within 3 months prior to participating in the study: stroke; obvious neurological dysfunction after stroke;
- •Patients with active gastrointestinal bleeding occurred within 3 months prior to participating in the study.
- •Poor control of hypertension determined by the researchers;
- •Previous or current malignancies (except for excised non melanoma skin cancer and carcinoma in situ);
- •It is known to have blood system diseases (including congenital and postnatal diseases, such as thalassemia, Fanconi anemia, aplastic anemia, myelodysplastic syndrome, hemolytic anemia, coagulation dysfunction, etc.) or other causes of anemia (such as fecal occult blood positive gastrointestinal hemorrhage or hookworm disease, etc.) ;
- •Known autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, anti neutrophil cytoplasmic antibody associated vasculitis, etc.);
- •Any previous functional organ transplant or scheduled organ transplant or no kidney.
- •Elective surgery that is expected to result in significant blood loss during the study period.
- •Serum albumin < 25 g / L;
- •Within 8 weeks before administration on the first day, the patients were treated with androgen, deferoxamine, deferrone or deferestrol.
- •Life expectancy < 12 months;
- •Transfusion within 4 weeks before administration on day 1, or is expected.
- •Intravenous iron supplementation and / or unwillingness to stop intravenous iron injection during the screening period;
- •Patients with drug abuse or addiction;
- •Have received any test drug within 4 weeks before inclusion or plan to receive other drug tests during the trial;
- •Women who can become pregnant must use contraception. Men with sexual partners who can become pregnant must use birth control, unless the man agrees to use contraception.
- •Any medical condition, that in the opinion of the study doctor, may pose a safety risk to the patient, may confound efficacy or safety assessment, or may interfere with study participation.
研究组 & 干预措施
HIF-PHI
HIF-PHI will be dosed orally three times a week.
干预措施: HIF-PHI (Drug)
Epoetin alfa
Epoetin alfa wull be disoensed per the package insert or the country-specific product labeling.
干预措施: Epoetin Alfa (Drug)
结局指标
主要结局
The incidence of cardiovascular and cerebrovascular events within 52 weeks.
时间窗: Week 0 to Week 52
Non fatal myocardial infarction, unstable angina, coronary artery bypass, coronary or peripheral vascular intervention, hospitalization due to heart failure, transient ischemic attack, stroke and death.
Mean Hemoglobin (Hb) change from baseline to average levels from Week 28 to Week 52.
时间窗: Minimum of 52 weeks and maximum of up to 3 years after last subject is randomized
For participants who did not have an available Hb value during the week 28-52 period, imputation rules were applied.
Proportion of subjects who achieve a Hb response during the first 24 weeks of treatment.
时间窗: Week 0 to Week 24
A Hb response is defined as: Hb ≥11.0g/dL and a Hb increase from baseline by ≥1.0g/dL in subjects whose baseline Hb \>8.0g/dL, or Increase in Hb ≥2.0g/dL in subjects whose baseline Hb ≤8.0g/dL.
次要结局
- The change of right ventricular systolic function(Weeks 12, 36, 52)
- The change of left ventricular structure(Weeks 12, 36, 52)
- The change of diastolic function(Weeks 12, 36, 52)
- BP effect 1: the proportion of subjects with increased hypertension(Week 0 to Week 27)
- Serum lipid parameters(Week 25 to Week 27)
- All cause mortality(Minimum of 52 weeks and maximum of up to 3 years after last subject is randomized)
- BP effect 2(Week 28 to Week 52)
- The change of left ventricular systolic function(Weeks 12, 36, 52)
- Inflammatory evaluation 1(Week 25 to Week 27)
- Inflammatory evaluation 2(Week 25 to Week 27)
- Inflammatory evaluation 3(Week 25 to Week 27)
- Inflammatory evaluation 4(Week 25 to Week 27)
研究者
Hong Liu
Director of Department of Nephrology
Second Xiangya Hospital of Central South University