Clinical trial NCT04134026: Evaluate the Efficacy and Safety of HIF-PHI for the Treatment of Anemia and Risks of Cardiovascular and Cerebrovascular Events in ESRD Newly Initiated Dialysis Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Anemia in Incident Dialysis Patients
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
First posted: 2019-10-21
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. The patient or his/her legal guardian signs the informed consent
2. Age ≥18 years
3. Weight: 45-100 kg (included)
4. 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
5. No iron deficiency.
6. No folate or Vitamin B12 deficiency.
7. No abnormal liver tests.
8. During the screening period, value of Hb is less than 10. 0 g / dl.

Exclusion Criteria:

1. Evidence of any clinically significant infection or active potential infection;
2. 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);
3. Patients with severe cardiovascular disease have had myocardial infarction, coronary artery bypass or PCI operation within 3 months prior to participating in the study.
4. Patients have experienced severe cerebrovascular diseases within 3 months prior to participating in the study: stroke; obvious neurological dysfunction after stroke;
5. Patients with active gastrointestinal bleeding occurred within 3 months prior to participating in the study.
6. Poor control of hypertension determined by the researchers;
7. Previous or current malignancies (except for excised non melanoma skin cancer and carcinoma in situ);
8. 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.) ;
9. Known autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, anti neutrophil cytoplasmic antibody associated vasculitis, etc.);
10. Any previous functional organ transplant or scheduled organ transplant or no kidney.
11. Elective surgery that is expected to result in significant blood loss during the study period.
12. Serum albumin \< 25 g / L;
13. Within 8 weeks before administration on the first day, the patients were treated with androgen, deferoxamine, deferrone or deferestrol.
14. Life expectancy \< 12 months;
15. Transfusion within 4 weeks before administration on day 1, or is expected.
16. Intravenous iron supplementation and / or unwillingness to stop intravenous iron injection during the screening period;
17. Patients with drug abuse or addiction;
18. Have received any test drug within 4 weeks before inclusion or plan to receive other drug tests during the trial;
19. 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.
20. 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.

Primary outcomes:
measure: Mean Hemoglobin (Hb) change from baseline to average levels from Week 28 to Week 52.
timeFrame: Minimum of 52 weeks and maximum of up to 3 years after last subject is randomized
measure: Proportion of subjects who achieve a Hb response during the first 24 weeks of treatment.
timeFrame: Week 0 to Week 24
measure: The incidence of cardiovascular and cerebrovascular events within 52 weeks.
timeFrame: Week 0 to Week 52
Secondary outcomes:
measure: All cause mortality
timeFrame: Minimum of 52 weeks and maximum of up to 3 years after last subject is randomized
measure: BP effect 1: the proportion of subjects with increased hypertension
timeFrame: Week 0 to Week 27
measure: BP effect 2
timeFrame: Week 28 to Week 52
measure: The change of left ventricular structure
timeFrame: Weeks 12, 36, 52
measure: The change of left ventricular systolic function
timeFrame: Weeks 12, 36, 52
measure: The change of right ventricular systolic function
timeFrame: Weeks 12, 36, 52
measure: The change of diastolic function
timeFrame: Weeks 12, 36, 52
measure: Serum lipid parameters
timeFrame: Week 25 to Week 27
measure: Inflammatory evaluation 1
timeFrame: Week 25 to Week 27
measure: Inflammatory evaluation 2
timeFrame: Week 25 to Week 27
measure: Inflammatory evaluation 3
timeFrame: Week 25 to Week 27
measure: Inflammatory evaluation 4
timeFrame: Week 25 to Week 27
Other outcomes:
measure: Serum iron level
timeFrame: Week 0 to Week 27
Locations:
city: Changsha
country: China
facility: Department of Nephrology, Second Xiangya Hospital, Central South University
state: Hunan
Study officials:
References:
citation: 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.