SGLT2 Inhibitors and Treatment of Heart Failure in Severe Renal Insufficiency

Study Overview
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Brief Summary
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In the treatment of heart failure (HF), SGLT-2 inhibitor (SGLT-2i) can significantly improve the clinical outcome and quality of life related to HF. The current data show that SGLT-2i is effective and safe in improving HF outcomes in patients with chronic kidney disease (CKD) stage 4, but there is little clinical evidence in patients with eGFR<20 ml/min/1.73 m2. Therefore, our research is designed to confirm that SGLT-2i can improve the outcome of HF in patients with chronic heart failure with reduced ejection fraction (HFrEF) and severe chronic renal insufficiency (eGFR<20ml/min/1.73m2).

Official Title
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The Efficacy and Safety of SGLT2 Inhibitors in Improving Heart Failure in Patients With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF) and Severe Renal Insufficiency

Conditions
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Heart Failure With Reduced Ejection Fraction, Renal Insufficiency, Chronic

Intervention / Treatment
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* Drug: SGLT-2 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20-75 years Patients with clinically confirmed chronic heart failure who have received treatment for heart failure according to the guidelines in the past two months, New York Heart Association (NYHA) grade II-IV Left ventricular ejection fraction (LVEF) ≤ 40% in the past 1 year Clinically confirmed chronic renal insufficiency, eGFR<20ml/min/1.73m2 or maintenance hemodialysis Exclusion Criteria: Allergy to SGLT-2i ALT or AST >3 times the upper limit of normal value; Or total bilirubin>2 times the upper limit of normal value Urinary or reproductive system infection in the last month Blood potassium is greater than or equal to the upper limit of normal value Patients with acute heart failure Patients who need intravenous diuretics before randomization, and the dose is greater than 40mg furosemide, or other equivalent intravenous loop diuretics Patients who need intravenous vasodilators, including nitrates, before randomization Systolic blood pressure<100mmHg measured during screening or at randomization Hemoglobin<90g/L Uncontrolled serious arrhythmia Myocardial infarction, unstable angina pectoris, hemorrhagic stroke or ischemic stroke in 90 days before randomization Proliferative retinopathy or macular disease, painful diabetes neuropathy, diabetes foot, diabetes ketoacidosis, hyperglycemic hyperosmolality that needed treatment in 90 days before randomization Patients with malignant tumors Drug or alcohol addicts Patients who have donated or transfused blood within 90 days before randomization, or are expected to donate or transfuse blood during the study period Pregnant or lactating women, or patients who cannot take reliable contraceptive measures during the study period Patients with uncontrolled abnormal thyroid function Type 1 diabetes Not suitable evaluated by the investigator

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br> | Drug: SGLT-2 inhibitor<br>* dapagliflozin<br>|
| No Intervention: Control group<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The quality of Life | The change of Quality of Life in patients by using the The Kansas City Cardiomyopathy Questionnaire(KCCQ) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The quality of Life | The change of Quality of Life in patients by using the KCCQ | 2 weeks, 4weeks and 8weeks | 
| Dose changes of diuretics | Dose changes of diuretics in subgroups of patients without dialysis | 12 weeks | 
| Changes of eGFR | Changes of eGFR in the subgroup of non-dialysis patients at 2 and 12 weeks | 2 and 12 weeks | 
| Changes of brain natriuretic peptide (BNP) | Changes of BNP | 12 weeks | 
| Changes of body weight | Changes of Body weight and BMI | 12 weeks |