Acute Kidney Injury, Cardiac Surgical Procedures
Conditions
Keywords
Acute Kidney Injury, Cardiac Surgery-Associated Acute Kidney Injury, Terbinafine, Randomized
Brief summary
Primary Objective: To evaluate the efficacy and safety of perioperative oral terbinafine in reducing the incidence of cardiac surgery-associated acute kidney injury (CSA-AKI).Secondary Objectives:To assess the effects of terbinafine on the severity of post-cardiac surgery AKI, length of hospital stay, and 30-day major adverse kidney events (MAKE30);To evaluate its impacts on biomarkers of renal injury and inflammation.
Interventions
DRUGTerbinafine
Terbinafine, an allylamine antifungal agent, is being repurposed for its potential antioxidant and anti-inflammatory properties to prevent acute kidney injury following cardiac surgery
Sponsors
Guangdong Provincial People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Aged ≥18 and ≤75 years, without restriction on gender. * Patients with a definite clinical diagnosis scheduled for elective cardiac and macrovascular surgery with cardiopulmonary bypass (CPB) support, including but not limited to coronary artery bypass grafting (CABG), cardiac valve replacement/repair, structural heart disease surgery, aortic arch plasty, or combined procedures of the above surgeries. * Classified as high risk by AKI risk scoring system, with a total score ≥4 points. * The subject or their legal representative shall fully understand the purpose, procedures, potential risks and benefits of this study, and voluntarily sign the written informed consent form.
Exclusion criteria
* Patients with severe chronic renal insufficiency (eGFR \< 50 mL/min/1.73 m² or serum creatinine \> 300 μmol/L), or those receiving any form of renal replacement therapy (e.g., hemodialysis, peritoneal dialysis). * Pre-existing acute kidney injury. * Presence of chronic or active liver diseases, including decompensated liver cirrhosis, active viral hepatitis, autoimmune liver disease, etc.; or preoperative laboratory tests showing ALT/AST ≥ 2 times the upper limit of normal (ULN). * Severe hematological diseases (preoperative white blood cell count \< 3.0 × 10⁹/L, platelet count \< 80 × 10⁹/L). * Uncontrolled active infections, or known immunodeficiency disorders (e.g., HIV infection, status post organ transplantation). * History of severe hypersensitivity to terbinafine or any excipients of its formulation. * Pregnant or lactating women, as well as women of childbearing potential who plan to conceive during the study and refuse to use effective contraception. * Participation in any other clinical trial of investigational drugs or medical devices within 3 months prior to screening. * Patients deemed inappropriate for enrollment in this study at the investigator's clinical discretion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of CSA-AKI at 7 Days Post-Surgery | From day of surgery through postoperative day 7 | Defined according to KDIGO criteria: SCr increase ≥26.5 μmol/L within 48h, or SCr increase ≥1.5× baseline within 7d, or urine output \<0.5 mL/kg/h for ≥6h. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum KDIGO Stage of AKI Within 7 Days Post-Surgery | From day of surgery through postoperative day 7 | AKI severity is assessed by the maximum KDIGO stage within 7 days post-surgery, based on serum creatinine and urine output criteria. Stage 1: SCr increase ≥26.5 μmol/L within 48h, or increase to 1.5-1.9× baseline within 7d, or urine output \<0.5 mL/kg/h for 6-12h; Stage 2: SCr increase to 2.0-2.9× baseline, or urine output \<0.5 mL/kg/h for ≥12h; Stage 3: SCr increase to ≥3.0× baseline, or SCr ≥353.6 μmol/L, or initiation of RRT, or urine output \<0.3 mL/kg/h for ≥24h, or anuria for ≥12h. The highest stage reached within the 7-day period is recorded. |
| Use of Renal Replacement Therapy Within 30 Days Post-Surgery | Within 30 days post-surgery | Documentation of whether the subject received any form of renal replacement therapy (including continuous renal replacement therapy, intermittent hemodialysis, peritoneal dialysis, etc.) within 30 days after surgery, based on clinical orders and treatment records. Binary outcome: yes/no. |
| Duration of ICU stay and total hospital length of stay | Postoperative day of ICU discharge (varies, captured at the time of discharge) and postoperative day of hospital discharge (varies, captured at the time of discharge) - with data reported as cumulative days up to 30 days for ICU and up to 60 days for hos | Data obtained from the hospital electronic medical record system or inpatient records. ICU stay is defined as the total number of days the subject spent in the ICU post-surgery (from ICU admission after surgery to ICU discharge). Total hospital length of stay is defined as the total number of days of hospitalization post-surgery (from the day of surgery to hospital discharge). |
| Major adverse cardiovascular events within 30 days (MACE30) | Within 30 days post-surgery | Data obtained from electronic medical records. MACE30 is defined as all-cause death, nonfatal myocardial infarction, or nonfatal stroke within 30 days post-surgery |
| Major adverse kidney events within 30 days (MAKE30) | Within 30 days post-surgery | Data obtained from electronic medical records. MAKE30 is defined as all-cause death, new RRT (any modality), or ≥25% decline in eGFR from baseline within 30 days post-surgery. eGFR is calculated using the CKD-EPI formula; baseline is defined as the most recent pre-operative value. |
| Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels | Pre-surgery (baseline), postoperative day 1, day 3, and day 7 or at hospital discharge, whichever came first. | Peripheral venous blood samples are collected and sent to the central laboratory for serum ALT and AST measurement using an automated biochemical analyzer. Normal reference ranges and assay methods follow each center's standard operating procedures. |
| Blood cell counts, including white blood cell count (WBC), red blood cell count (RBC), and platelet count (PLT) | Postoperative day 1, day 3, and day 7 or at hospital discharge, whichever came first. | Peripheral venous blood samples are collected and measured using an automated hematology analyzer |
| Incidence of adverse events, including dysgeusia, rash, and gastrointestinal reactions (nausea, vomiting, diarrhea, abdominal pain, etc.) | From post-surgery to discharge (within 30-day follow-up period) | Adverse events are recorded based on investigator inquiry and subject self-report, including event name, onset time, severity, duration, outcome, and causality with the study drug. Severity is graded according to CTCAE 5.0 criteria (Grade 1-5), and causality with the study drug is determined by the investigator |
Countries
China
Contacts
CONTACTQiquan Sun, Professor
Outcome results
None listed