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Evaluate the Efficacy and Safety of Roxadustat for the Treatment of Anemia and Risks of Cardiovascular and Cerebrovascular Events in ESRD Newly Initiated Dialysis Patients

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ClinicalTrials.gov Identifier: NCT04134026
Recruitment Status : Recruiting
First Posted : October 21, 2019
Last Update Posted : October 21, 2019
Sponsor:
Information provided by (Responsible Party):
Hong Liu, Second Xiangya Hospital of Central South University

Tracking Information
First Submitted Date  ICMJE October 16, 2019
First Posted Date  ICMJE October 21, 2019
Last Update Posted Date October 21, 2019
Estimated Study Start Date  ICMJE October 20, 2019
Estimated Primary Completion Date October 19, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2019)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2019)
  • All cause mortality [ Time Frame: Minimum of 52 weeks and maximum of up to 3 years after last subject is randomized ]
    The incidence of death events.
  • BP effect 1: the proportion of subjects with increased hypertension [ Time Frame: Week 0 to Week 27 ]
    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 [ Time Frame: Week 28 to Week 52 ]
    Mean BP change from baseline to average levels from Week 28 to Week 52.
  • The change of left ventricular structure [ Time Frame: Weeks 12, 36, 52 ]
    Standardized ECHO evaluates left ventricular volume index (ml/m2).
  • The change of left ventricular systolic function [ Time Frame: Weeks 12, 36, 52 ]
    Standardized ECHO evaluates left ventricular ejection fraction (%).
  • The change of right ventricular systolic function [ Time Frame: Weeks 12, 36, 52 ]
    Systolic lateral tricuspid annulus velocity (S') was measured by tissue Doppler.
  • The change of diastolic function [ Time Frame: Weeks 12, 36, 52 ]
    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 [ Time Frame: Week 25 to Week 27 ]
    Mean change in low-density lipoprotein (LDL) cholesterol.
  • Inflammatory evaluation 1 [ Time Frame: Week 25 to Week 27 ]
    Mean change level of CRP.
  • Inflammatory evaluation 2 [ Time Frame: Week 25 to Week 27 ]
    Mean change level of IL-2
  • Inflammatory evaluation 3 [ Time Frame: Week 25 to Week 27 ]
    Mean change level of IL-6
  • Inflammatory evaluation 4 [ Time Frame: Week 25 to Week 27 ]
    Mean change level of IL-17A
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 17, 2019)
Serum iron level [ Time Frame: Week 0 to Week 27 ]
Mean change of iron from baseline to level at the 27th week.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Evaluate the Efficacy and Safety of Roxadustat for the Treatment of Anemia and Risks of Cardiovascular and Cerebrovascular Events in ESRD Newly Initiated Dialysis Patients
Official Title  ICMJE Phase 4, Multicenter, Randomized, Open-Lable, Active-Controlled Study of the Efficacy and Safty of Roxadustat for the Treatment of Anemia and Risks of Cardiovascular and Cerebrovascular Events in Incident-Dialysis Patients
Brief Summary The purpose of the study is to determin whether Roxadustat 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 Roxadustat or Active Control (Epoetin alfa).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Anemia in Incident Dialysis Patients
Intervention  ICMJE
  • Drug: Roxadustat
    Drug will be dosed orally three times a week.
    Other Name: FG-4592
  • Drug: Epoetin Alfa
    The drug will be dispensed per the package insert or the country-specific product labeling.
    Other Name: Epogen
Study Arms  ICMJE
  • Experimental: Roxadustat
    Roxadustat will be dosed orally three times a week.
    Intervention: Drug: Roxadustat
  • Active Comparator: Epoetin alfa
    Epoetin alfa wull be disoensed per the package insert or the country-specific product labeling.
    Intervention: Drug: Epoetin Alfa
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 17, 2019)
400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 19, 2023
Estimated Primary Completion Date October 19, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04134026
Other Study ID Numbers  ICMJE CSU-SXH-CT-2019-015
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hong Liu, Second Xiangya Hospital of Central South University
Study Sponsor  ICMJE Second Xiangya Hospital of Central South University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Second Xiangya Hospital of Central South University
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP