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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

Primary Purpose

Anemia in Incident Dialysis Patients

Status
Not yet recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
HIF-PHI
Epoetin Alfa
Sponsored by
Second Xiangya Hospital of Central South University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia in Incident Dialysis Patients

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Department of Nephrology, Second Xiangya Hospital, Central South University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

HIF-PHI

Epoetin alfa

Arm Description

HIF-PHI will be dosed orally three times a week.

Epoetin alfa wull be disoensed per the package insert or the country-specific product labeling.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

All cause mortality
The incidence of death events.
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.
BP effect 2
Mean BP change from baseline to average levels from Week 28 to Week 52.
The change of left ventricular structure
Standardized ECHO evaluates left ventricular volume index (ml/m2).
The change of left ventricular systolic function
Standardized ECHO evaluates left ventricular ejection fraction (%).
The change of right ventricular systolic function
Systolic lateral tricuspid annulus velocity (S') was measured by tissue Doppler.
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.
Serum lipid parameters
Mean change in low-density lipoprotein (LDL) cholesterol.
Inflammatory evaluation 1
Mean change level of CRP.
Inflammatory evaluation 2
Mean change level of IL-2
Inflammatory evaluation 3
Mean change level of IL-6
Inflammatory evaluation 4
Mean change level of IL-17A

Full Information

First Posted
October 16, 2019
Last Updated
May 20, 2021
Sponsor
Second Xiangya Hospital of Central South University
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1. Study Identification

Unique Protocol Identification Number
NCT04134026
Brief Title
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

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 20, 2022 (Anticipated)
Primary Completion Date
October 19, 2023 (Anticipated)
Study Completion Date
October 19, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Second Xiangya Hospital of Central South University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia in Incident Dialysis Patients

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HIF-PHI
Arm Type
Experimental
Arm Description
HIF-PHI will be dosed orally three times a week.
Arm Title
Epoetin alfa
Arm Type
Active Comparator
Arm Description
Epoetin alfa wull be disoensed per the package insert or the country-specific product labeling.
Intervention Type
Drug
Intervention Name(s)
HIF-PHI
Intervention Description
Drug will be dosed orally three times a week.
Intervention Type
Drug
Intervention Name(s)
Epoetin Alfa
Other Intervention Name(s)
Epogen
Intervention Description
The drug will be dispensed per the package insert or the country-specific product labeling.
Primary Outcome Measure Information:
Title
Mean Hemoglobin (Hb) change from baseline to average levels from Week 28 to Week 52.
Description
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
Title
Proportion of subjects who achieve a Hb response during the first 24 weeks of treatment.
Description
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
Title
The incidence of cardiovascular and cerebrovascular events within 52 weeks.
Description
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
Secondary Outcome Measure Information:
Title
All cause mortality
Description
The incidence of death events.
Time Frame
Minimum of 52 weeks and maximum of up to 3 years after last subject is randomized
Title
BP effect 1: the proportion of subjects with increased hypertension
Description
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
Title
BP effect 2
Description
Mean BP change from baseline to average levels from Week 28 to Week 52.
Time Frame
Week 28 to Week 52
Title
The change of left ventricular structure
Description
Standardized ECHO evaluates left ventricular volume index (ml/m2).
Time Frame
Weeks 12, 36, 52
Title
The change of left ventricular systolic function
Description
Standardized ECHO evaluates left ventricular ejection fraction (%).
Time Frame
Weeks 12, 36, 52
Title
The change of right ventricular systolic function
Description
Systolic lateral tricuspid annulus velocity (S') was measured by tissue Doppler.
Time Frame
Weeks 12, 36, 52
Title
The change of diastolic function
Description
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
Title
Serum lipid parameters
Description
Mean change in low-density lipoprotein (LDL) cholesterol.
Time Frame
Week 25 to Week 27
Title
Inflammatory evaluation 1
Description
Mean change level of CRP.
Time Frame
Week 25 to Week 27
Title
Inflammatory evaluation 2
Description
Mean change level of IL-2
Time Frame
Week 25 to Week 27
Title
Inflammatory evaluation 3
Description
Mean change level of IL-6
Time Frame
Week 25 to Week 27
Title
Inflammatory evaluation 4
Description
Mean change level of IL-17A
Time Frame
Week 25 to Week 27
Other Pre-specified Outcome Measures:
Title
Serum iron level
Description
Mean change of iron from baseline to level at the 27th week.
Time Frame
Week 0 to Week 27

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 10. 0 g / dl. 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. 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.
Facility Information:
Facility Name
Department of Nephrology, Second Xiangya Hospital, Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hong Liu, MD,phD
Phone
86-0731-85292057
Email
liuh0618@163.com
First Name & Middle Initial & Last Name & Degree
Hong Liu, MD,phD

12. IPD Sharing Statement

Citations:
PubMed Identifier
36005278
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.
Results Reference
derived

Learn more about this trial

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

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