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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HIF-PHI | Experimental | HIF-PHI will be dosed orally three times a week. |
|
| Epoetin alfa | Active Comparator | Epoetin alfa wull be disoensed per the package insert or the country-specific product labeling. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HIF-PHI | Drug | Drug will be dosed orally three times a week. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | Week 0 to Week 52 |
| Measure | Description | Time Frame |
|---|---|---|
| All cause mortality | The incidence of death events. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Serum iron level | Mean change of iron from baseline to level at the 27th week. | Week 0 to Week 27 |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Nephrology, Second Xiangya Hospital, Central South University | Changsha | Hunan | 410000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36005278 | Derived | Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2. |
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| Epoetin Alfa |
| Drug |
The drug will be dispensed per the package insert or the country-specific product labeling. |
|
|
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.
| Week 0 to Week 27 |
| BP effect 2 | Mean BP change from baseline to average levels from Week 28 to Week 52. | Week 28 to Week 52 |
| The change of left ventricular structure | Standardized ECHO evaluates left ventricular volume index (ml/m2). | Weeks 12, 36, 52 |
| The change of left ventricular systolic function | Standardized ECHO evaluates left ventricular ejection fraction (%). | Weeks 12, 36, 52 |
| The change of right ventricular systolic function | Systolic lateral tricuspid annulus velocity (S') was measured by tissue Doppler. | 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. | Weeks 12, 36, 52 |
| Serum lipid parameters | Mean change in low-density lipoprotein (LDL) cholesterol. | Week 25 to Week 27 |
| Inflammatory evaluation 1 | Mean change level of CRP. | Week 25 to Week 27 |
| Inflammatory evaluation 2 | Mean change level of IL-2 | Week 25 to Week 27 |
| Inflammatory evaluation 3 | Mean change level of IL-6 | Week 25 to Week 27 |
| Inflammatory evaluation 4 | Mean change level of IL-17A | Week 25 to Week 27 |
| ID | Term |
|---|---|
| D000068817 | Epoetin Alfa |
| ID | Term |
|---|---|
| D004921 | Erythropoietin |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
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