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

NCT07027774 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: FAW2024104
• Study Type: interventional
• Target: 429
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter, prospective, randomized, controlled study that will enroll approximately 429 subjects. The screening period will last 4-8 weeks. Subjects will undergo pre-screening based on eGFR and urinary albumin-to-creatinine ratio (UACR). Only non-dialysis subjects meeting the following criteria confirmed by local laboratories within 6 months prior to screening will be eligible for central laboratory screening: 10 mL/min/1.73m² ≤ eGFR \< 30 mL/min/1.73m² and 150 mg/g (16.95 mg/mmol) ≤ UACR \< 5000 mg/g (565 mg/mmol). Unless contraindicated due to intolerance, subjects with 20 mL/min/1.73m² ≤ eGFR \< 30 mL/min/1.73m² must receive stable, maximally tolerated labeled daily doses of ACEi or ARB for at least 4 weeks prior to randomization. For subjects with 10 mL/min/1.73m² ≤ eGFR \< 20 mL/min/1.73m², investigators will determine ACEi/ARB treatment based on patient condition per KDIGO guidelines. Other antihypertensive, lipid-lowering, and glucose-lowering therapies should be stabilized for approximately 4 weeks before randomization. Investigators are encouraged to maintain stability of medications known to affect serum creatinine levels during screening and approximately 2 weeks prior to any serum chemistry measurements throughout the study. Eligible subjects will be randomized in a 1:1:1 ratio to receive Henagliflozin (10 mg q.d., 5 mg q.d.) or conventional therapy. Thereafter, subjects will undergo laboratory assessments, concomitant medication review, adverse event collection, and clinical endpoint ascertainment at Week 4 (Day 30), Week 12 (Day 90), and Week 24 (Day 180), followed by every 12-week intervals. Throughout the study, all subjects will receive glycemic, blood pressure (target SBP \<140 mmHg and DBP \<90 mmHg), and lipid management according to current guidelines. All subjects will complete an end-of-study visit. Subjects discontinuing study drug prematurely should continue all subsequent study visits.

Conditions

Chronic Kidney Disease Stage 4

Outcome Measures

Primary Outcomes (1)

• eGFR total slope change from 4 to 52 weeks

  52 weeks

Secondary Outcomes (9)

• Total eGFR slope at 1 year post-randomization

  56 weeks

• Composite endpoint of kidney disease progression ，hospitalization for heart failure, or cardiovascular death.

  56 weeks

• Kidney disease progression (sustained eGFR decline ≥40%, sustained eGFR <7.5 mL/min/1.73m², initiation of maintenance dialysis or kidney transplantation, or kidney death).

  56 weeks

• Composite endpoint of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure)

  56 weeks

• Composite endpoint of initiation of maintenance dialysis or kidney transplantation, kidney death, or cardiovascular death.

  56 weeks

Study Arms (3)

Henagliflozin 5mg Group

EXPERIMENTAL

Henagliflozin 5 mg once daily + RAASi-based comprehensive strategy (optional)

Drug: Henagliflozin 5 mg Group

Henagliflozin 10mg Group

EXPERIMENTAL

Henagliflozin 10 mg once daily + RAASi-based comprehensive strategy (optional)

Drug: Henagliflozin 10 mg Group

Conventional therapy group

ACTIVE COMPARATOR

RAASi-based comprehensive strategy (e.g., ramipril + lipid control + glycemic management)

Drug: Conventional therapy group

Interventions

Henagliflozin 5 mg Group DRUG

Henagliflozin 5 mg once daily plus KDIGO-based comprehensive management strategy (e.g., RAAS inhibitors）

Henagliflozin 5mg Group

Henagliflozin 10 mg Group DRUG

Henagliflozin 10 mg once daily plus KDIGO-based comprehensive management strategy (e.g., RAAS inhibitors）

Henagliflozin 10mg Group

Conventional therapy group DRUG

KDIGO-based comprehensive management strategy (e.g., RAAS inhibitors）

Conventional therapy group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The investigator considers that the participant does not require Henagliflozin or any other SGLT-2 inhibitor therapy, nor deems such therapy absolutely inappropriate; and based on local laboratory results within 6 months before the screening visit and at the screening visit, the following criteria must be met:
• mL/min/1.73m² ≤ eGFR \< 30 mL/min/1.73m² (CKD-EPI equation), and
• mg/g (16.95 mg/mmol) ≤ Urine Albumin-to-Creatinine Ratio (UACR) \< 5000 mg/g (565 mg/mmol)
• Age ≥ 18 years, male or femal
• Participants with 20 mL/min/1.73m² ≤ eGFR \< 30 mL/min/1.73m² must be on a stable and tolerated dose of an ACE inhibitor (ACEI) or ARB for at least 4 weeks, unless intolerant (reasons for intolerance must be documented). Participants with 10 mL/min/1.73m² ≤ eGFR \< 20 mL/min/1.73m² should have ACEI/ARB use determined by the investigator based on the patient's clinical status and KDIGO guideline recommendations;
• Anticipated time to requiring dialysis is greater than 1 month;
• Provision of written informed consent (illiterate participants may use a thumbprint in lieu of a signature).

You may not qualify if:

• 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:
• Did not adhere to the run-in treatment;

Sponsors & Collaborators

• First Affiliated Hospital of Wannan Medical College: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

henagliflozin; Population Groups

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: June 18, 2025
• Study Start: July 10, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: June 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share