Nafamostat Mesylate Versus Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy in Sepsis-Associated Acute Kidney Injury

About this trial

Last updated 2 months ago

Study ID

2026ZDSYLL076-P01

Status

Not yet recruiting

Type

Interventional

Phase

Phase 4

Placebo

Accepting

18 to 90 Years

All Sexes

Trial Timing

Started 2 months ago

What is this trial about?

Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and often requires continuous kidney replacement therapy (CRRT). The choice of blood thinner (anticoagulation) during CRRT affects how long the filter works and the risk of bleeding. Citrate is the current standard blood thinner, but it can cause metabolic problems in patients with shock or liver dysfunction. Nafamostat mesylate (NM) is a newer alternative with a very short half-life and local action, which may offer both effectiveness and safety. However, no large, high-quality study has directly compared NM with citrate in SA-AKI patients. This study aims to show that NM is not worse than citrate for a key outcome called MAKE30 (a combination of death, continued need for kidney replacement therapy, or persistent kidney dysfunction at 30 days). We will also compare filter life, kidney recovery, death rates, hospital stay, bleeding events, and other outcomes. This is a multicenter, randomized, single-blind, non-inferiority trial. A total of 1162 patients will be assigned equally to receive either NM or citrate during CRRT. Patients will not know which treatment they get, but healthcare providers will know. The study includes adults aged 18-90 with sepsis and severe acute kidney injury requiring CRRT for more than 48 hours, who have given informed consent. Key exclusions include active bleeding risk, severe liver failure, pregnancy, or participation in another trial within 3 months. The main outcome is MAKE30 at 30 days. Secondary outcomes include filter life, days off CRRT, death rates, length of stay, bleeding, and changes in organ failure scores. Safety monitoring will focus on metabolic problems and citrate accumulation. The study is designed to test whether NM is non-inferior to citrate with a margin of 5%. If non-inferiority is shown, we will also test if NM is superior. Analyses will follow intention-to-treat principles.

What are the participation requirements?

Inclusion Criteria

* Age 18-90 years, inclusive, of either sex.

* Meets the Sepsis-3 diagnostic criteria.

* After adequate resuscitation, still meets KDIGO stage 2 or 3 AKI criteria (2012 version), satisfying any one of the following: (a) SCr > 2 times baseline; (b) urine output < 0.5 mL/kg/h for at least 12 hours; (c) SCr > 3 times baseline; (d) SCr >= 4.0 mg/dL [353.6 umol/L]; (e) urine output < 0.3 mL/kg/h for at least 24 hours; or (f) anuria (minimal or no urine output) for at least 12 hours.

* Judged by the treating clinician to require CRRT.

* Expected CRRT duration > 48 hours.

* Signed informed consent form. Exclusion Criteria

* Requirement for therapeutic anticoagulation (e.g., PE, DVT).

* Contraindication to systemic anticoagulation.

* Hemolytic uremic syndrome or thrombotic thrombocytopenic purpura.

* Acute liver failure and/or shock with persistent severe lactic acidosis (pH < 7.2 on two consecutive tests for more than 2 hours and lactate > 72.1 mg/dL [8 mmol/L]).

* Severe hematologic disease, advanced malignancy, or other end-stage disease.

* CKD receiving long-term maintenance dialysis.

* AKI caused by permanent bilateral renal artery occlusion or surgical injury.

* AKI caused by glomerulonephritis, interstitial nephritis, or vasculitis.

* Current use of immunosuppressants.

* Signed DNR order.

* Known allergy to the study drugs (nafamostat mesylate or sodium citrate) or their excipients.

* Kidney transplantation within the past year.

* Planning pregnancy in the near term, pregnancy, or lactation.

* HIV infection.

* Participation in another clinical trial within the past 3 months.

* Any other condition deemed unsuitable for enrollment by the investigator.