Effect of Henagliflozin on Renal Outcomes in Non-dialysis Patients With Advanced Chronic Kidney Disease : A Multicenter Prospective, Randomized Controlled Trial（HERO -aCKD）

Received SGLT2 inhibitor treatment within 8 weeks prior to enrollment or with a history of SGLT2 inhibitor intolerance;

Receiving combined therapy with an ACE inhibitor (ACEi) and an ARB, or a renin inhibitor combined with ACEi or ARB (based on self-report at screening and randomization visits);

On maintenance dialysis, has a functioning kidney transplant, or is a planned living donor transplant recipient (based on self-report at screening and randomization visits);

Polycystic kidney disease, active lupus nephritis, or systemic vasculitis;(5) Symptomatic hypotension, or systolic blood pressure \<90 mmHg or \>180 mmHg at screening;

ALT or AST levels \>3 times the upper limit of normal (ULN) at screening;

Received any intravenous immunosuppressive therapy within the previous 3 months; or any subject who received prednisone \>45 mg/day (or equivalent dose) within the previous 3 months;

Current use or use within 12 weeks prior to enrollment of glucagon-like peptide-1 (GLP-1) receptor agonist medications (e.g., liraglutide, semaglutide, dulaglutide, etc.) or current participation in another clinical trial of glucose-lowering drugs that may affect kidney or cardiovascular outcomes;(9) Severe malnutrition (serum albumin \<25 g/L) and/or severe anemia (hemoglobin \<70 g/L);

Known poor adherence to clinical follow-up or medication;

Myocardial infarction, unstable angina, or stroke within 12 weeks prior to enrollment;

Underwent coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary artery bypass grafting \[CABG\]) or valve repair/replacement within 12 weeks prior to enrollment, or plans to undergo any of these procedures after randomization;(13) Any disease other than kidney or cardiovascular disease (e.g., but not limited to, malignancy) that, in the investigator's clinical judgment, is associated with a life expectancy of less than 2 years;

Active malignancy requiring treatment at the time of the first visit (except for successfully treated basal cell carcinoma, treated squamous cell carcinoma, or thyroid cancer);

Currently pregnant, breastfeeding, or a woman of childbearing potential (WOCBP) unless using a highly effective method of contraception;

Type 1 diabetes;(17) Investigator considers the patient unable to understand and/or comply with the study procedures and/or follow-up, or any condition that, in the investigator's opinion, may lead to the patient's inability to complete the study.

Additionally, subjects will be excluded at the randomization visit if any of the following occur:

1. Did not adhere to the run-in treatment;

2. No longer willing to be randomized and followed for at least 2 years;

3. Considered unsuitable for randomization by the local investigator; OR experienced ketoacidosis, heart attack (myocardial infarction), stroke, hospitalization for heart failure, hospitalization for urinary tract infection, or acute kidney injury during the run-in period.

What this study is about