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.
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
400
Drug will be dosed orally three times a week.
The drug will be dispensed per the package insert or the country-specific product labeling.
Department of Nephrology, Second Xiangya Hospital, Central South University
Changsha, Hunan, China
Mean Hemoglobin (Hb) change from baseline to average levels from Week 28 to Week 52.
For participants who did not have an available Hb value during the week 28-52 period, imputation rules were applied.
Time frame: Minimum of 52 weeks and maximum of up to 3 years after last subject is randomized
Proportion of subjects who achieve a Hb response during the first 24 weeks of treatment.
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.
Time frame: Week 0 to Week 24
The incidence of cardiovascular and cerebrovascular events within 52 weeks.
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.
Time frame: Week 0 to Week 52
All cause mortality
The incidence of death events.
Time frame: Minimum of 52 weeks and maximum of up to 3 years after last subject is randomized
BP effect 1: the proportion of subjects with increased hypertension
Blood pressure (BP) increased compared to pre-dialysis BP: the delta systolic BP ≥ 20 mmHg and systolic blood pressure ≥ 170 mmHg, or the delta diastolic BP ≥ 15 mmHg and diastolic BP ≥ 100 mmHg.
Time frame: Week 0 to Week 27
BP effect 2
Mean BP change from baseline to average levels from Week 28 to Week 52.
Time frame: Week 28 to Week 52
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The change of left ventricular structure
Standardized ECHO evaluates left ventricular volume index (ml/m2).
Time frame: Weeks 12, 36, 52
The change of left ventricular systolic function
Standardized ECHO evaluates left ventricular ejection fraction (%).
Time frame: Weeks 12, 36, 52
The change of right ventricular systolic function
Systolic lateral tricuspid annulus velocity (S') was measured by tissue Doppler.
Time frame: Weeks 12, 36, 52
The change of diastolic function
Left ventricular diastolic function was measured based on the integration of the ratio of early (E wave) and late (A wave) mitral inflow, mitral E wave deceleration time, E/e' ratio (e' being the tissue Doppler velocity of the medial annulus), E/A changes with Valsalva maneuver, and pattern of pulmonary vein flow. The data will be combine to report diastolic function.
Time frame: Weeks 12, 36, 52
Serum lipid parameters
Mean change in low-density lipoprotein (LDL) cholesterol.
Time frame: Week 25 to Week 27
Inflammatory evaluation 1
Mean change level of CRP.
Time frame: Week 25 to Week 27
Inflammatory evaluation 2
Mean change level of IL-2
Time frame: Week 25 to Week 27
Inflammatory evaluation 3
Mean change level of IL-6
Time frame: Week 25 to Week 27
Inflammatory evaluation 4
Mean change level of IL-17A
Time frame: Week 25 to Week 27