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

Summary

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.

Conditions

• Sepsis
• Acute Kidney Injury
• Continuous Renal Replacement Therapy (CRRT)

Interventions

DRUG

Citrate anticoagulation

Citrate (3% or 4% trisodium citrate solution) is a regional anticoagulant that chelates ionized calcium in the extracorporeal circuit, thereby inhibiting the coagulation cascade. The control product is supplied as an injection solution. It should be stored in a tightly closed container. During CRRT, citrate is infused pre-filter (before the blood pump) and requires separate systemic calcium replacement to maintain normal ionized calcium levels.

DRUG

Nafamostat Mesylate

Nafamostat mesylate is a synthetic serine protease inhibitor with a very short half-life (approximately 8 minutes). It acts locally as an anticoagulant by inhibiting thrombin, factor Xa, and other coagulation proteases. The investigational product is supplied as a lyophilized powder for injection. It must be protected from light and stored below 25 °C. For use during continuous renal replacement therapy (CRRT), the powder is reconstituted and administered as a continuous pre-filter infusion.

Sponsors & Collaborators

• Southeast University, China

  collaborator OTHER

• Jianfeng Xie

  lead OTHER

Principal Investigators

• Yingzi Huang · Zhongda Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-01

Primary Completion

2028-04-01

Completion

2028-06-01