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
Overview
- Phase
- Phase 4
- Intervention
- HIF-PHI
- Conditions
- Anemia in Incident Dialysis Patients
- Sponsor
- Second Xiangya Hospital of Central South University
- Enrollment
- 400
- Locations
- 1
- Primary Endpoint
- The incidence of cardiovascular and cerebrovascular events within 52 weeks.
- Status
- Not yet recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
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.
Detailed Description
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).
Investigators
Hong Liu
Director of Department of Nephrology
Second Xiangya Hospital of Central South University
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
HIF-PHI
HIF-PHI will be dosed orally three times a week.
Intervention: HIF-PHI
Epoetin alfa
Epoetin alfa wull be disoensed per the package insert or the country-specific product labeling.
Intervention: Epoetin Alfa
Outcomes
Primary Outcomes
The incidence of cardiovascular and cerebrovascular events within 52 weeks.
Time Frame: 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.
Time Frame: 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.
Time Frame: 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.
Secondary Outcomes
- 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)