Study of the Safety and Efficacy of Roxadustat in the Treatment of Heart Failure With Chronic Kidney Disease and Anemia

Sponsor

China-Japan Friendship Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05691257

Collaborator

(none)

300

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to conduct a a cohort study to evaluate the efficacy and safety of the efficacy and safety of roxadustat for the treatment of anemia, quality of life and cardiac function in patients with heart failure and chronic kidney disease.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure Chronic Kidney Diseases Anemia	Drug: Roxadustat Drug: Recombinant human eythropoietin and/or Iron agents	Phase 4

Detailed Description

This is a cohort study in patients with anemia with heart failure complicated with chronic kidney disease, evaluating the the efficacy and safety of roxadustat. Patients were divided into roxadustat group and control group according to whether roxadustat was used or not. The efficacy and safety of roxadustat for the treatment of anemia, quality of life and cardiac function in patients with heart failure and chronic kidney disease will be evaluated.

The primary and secondary endpoints will be examined in subgroups determined by baseline variables reflecting demography, heart failure characteristics, diabetes status, kidney function, cardiac function, natriuretic peptide, dialysis, and additional co-morbidities, concomitant medications, and others.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study of the Safety and Efficacy of Roxadustat in the Treatment of Heart Failure With Chronic Kidney Disease and Anemia

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Roxadustat group Roxadustat group: patients with heart failure and chronic kidney disease and anemia treated with roxadustat and other anemia correction drugs.	Drug: Roxadustat The initial dose of roxadustat was given according to body weight, which was more than 60kg: 100mg (three times a week); Weight less than 60kg: 70mg (three times a week); 2 weeks later, the corresponding indexes were rechecked and medication was adjusted according to hemoglobin. The target is hemoglobin 100-120g/L. Reference for medication Method: The use of roxadustat is the same as the RCT study of roxadustat in the treatment of anemia and the drug instructions of roxadustat published by N Engl J Med in 2019. Drug: Recombinant human eythropoietin and/or Iron agents Other drugs to treat anemia include: Recombinant human eythropoietin (RH-EPO), iron agents (ferrous succinate, polysaccharide iron complex, iron sucrose, etc.)
Other: Control group Control group: patients with heart failure and chronic kidney disease and anemia who were treated with other drugs include: Recombinant human eythropoietin (RH-EPO), iron agents (ferrous succinate, polysaccharide iron complex, iron sucrose, etc.)	Drug: Recombinant human eythropoietin and/or Iron agents Other drugs to treat anemia include: Recombinant human eythropoietin (RH-EPO), iron agents (ferrous succinate, polysaccharide iron complex, iron sucrose, etc.)

Arm

Intervention/Treatment

Experimental: Roxadustat group

Roxadustat group: patients with heart failure and chronic kidney disease and anemia treated with roxadustat and other anemia correction drugs.

Drug: Roxadustat

The initial dose of roxadustat was given according to body weight, which was more than 60kg: 100mg (three times a week); Weight less than 60kg: 70mg (three times a week); 2 weeks later, the corresponding indexes were rechecked and medication was adjusted according to hemoglobin. The target is hemoglobin 100-120g/L. Reference for medication Method: The use of roxadustat is the same as the RCT study of roxadustat in the treatment of anemia and the drug instructions of roxadustat published by N Engl J Med in 2019.

Drug: Recombinant human eythropoietin and/or Iron agents

Other drugs to treat anemia include: Recombinant human eythropoietin (RH-EPO), iron agents (ferrous succinate, polysaccharide iron complex, iron sucrose, etc.)

Other: Control group

Control group: patients with heart failure and chronic kidney disease and anemia who were treated with other drugs include: Recombinant human eythropoietin (RH-EPO), iron agents (ferrous succinate, polysaccharide iron complex, iron sucrose, etc.)

Drug: Recombinant human eythropoietin and/or Iron agents

Other drugs to treat anemia include: Recombinant human eythropoietin (RH-EPO), iron agents (ferrous succinate, polysaccharide iron complex, iron sucrose, etc.)

Outcome Measures

Primary Outcome Measures

Change in the hemoglobin from baseline [up to 8 week]
Hemoglobin is calculated by the routine blood test

Secondary Outcome Measures

Change in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) [Up to 8 weeks]
Change from baseline to week 12 in N-terminal pro-brain natriuretic peptide (NT-proBNP). Baseline value was defined as the mean of all available measurements from the screening visit until start of treatment with randomised study medication.
Change in Left Ventricular Systolic Function [Up to 24 weeks]
Change in left ventricular ejection fraction is assessed by two-dimensional directed M-mode echocardiography
Change in Left Ventricular End-Diastolic Diameter [Up to 24 weeks]
Change in left ventricular end-diastolic diameter is assessed by two-dimensional directed M-mode echocardiography
Change in Left Ventricular Diastolic Function [Up to 24 weeks]
Change in E/e' is assessed by two-dimensional directed M-mode echocardiography
Change in Low-density lipoprotein（LDL） [Up to 8 weeks]
Change from baseline to week 8 in Low-density lipoprotein（LDL）.Baseline value was defined as the mean of all available measurements from the screening visit until start of treatment with randomised study medication.
Change in Serum ferritin [Up to 8 weeks]
Change from baseline to week 8 in Serum ferritin.Baseline value was defined as the mean of all available measurements from the screening visit until start of treatment with randomised study medication.
Change in Transferrin saturation [Up to 8 weeks]
Change from baseline to week 8 in Transferrin saturation.Baseline value was defined as the mean of all available measurements from the screening visit until start of treatment with randomised study medication.
Change in Left atrial volume [Up to 24 weeks]
Change in left atrial volume is assessed by two-dimensional directed M-mode echocardiography
Change in Left atrial volume index [Up to 24 weeks]
Change in left atrial volume index is assessed by two-dimensional directed M-mode echocardiography

Other Outcome Measures

Liver Injury [Up to 8 weeks]
Liver injury is defined as: i) a rise of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to 3 times above the upper limit of normal [ULN], or ii) a rise of total bilirubin to 2 times above the upper limit of normal [ULN]
Hyperkalemia [Up to 8 weeks]
Hyperkalemia is defined as：Serum potassium > 5.5 mmol/L
Thromboembolism [Up to 1 year]
Thromboembolism is defined as：Deep vein thrombosis at follow-up

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, aged ≥18 years at the time of consent
Weight between 45-160kg
Definite diagnosis of heart failure: according to the diagnostic criteria for heart failure in "Chinese Heart Failure Diagnosis and Treatment Guidelines 2018"
eGFR <60mL/min/1.73 m^2 by CKD-EPI.
Diagnosed anemia: male hemoglobin <130 g/L, non-pregnant female hemoglobin <120 g/L.
Provision of signed informed consent prior to any study specific procedures.

Exclusion Criteria:

Acute or chronic active bleeding 6 months before enrollment.
Anemias due to thalassemia, sickle cell anemia, pure red aplastic anemia, hemolytic anemia, ect.
Thromboembolism requiring anticoagulation.
Severe Infection.
Hepatic impairment aspartate transaminase [AST] or alanine transaminase [ALT] >3x the upper limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment).
Severe malnutrition.
Women of child-bearing potential who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator OR women who have a positive pregnancy test at enrolment or randomization OR women who are breast-feeding.
Patients who have received roxadustat treatment or are allergic to roxadustat.