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

NCT07518303 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2026ZDSYLL076-P01
• Study Type: interventional
• Target: 1,162
• Locations: 0 countries
• Sites: N/A

Brief Summary

This multicenter, randomized, open-label, active-controlled, parallel-group trial will evaluate the efficacy and safety of nafamostat mesylate anticoagulation compared with regional citrate anticoagulation in adult patients with sepsis-associated acute kidney injury requiring continuous renal replacement therapy. Eligible participants will be randomized in a 1:1 ratio to receive either nafamostat mesylate or regional citrate anticoagulation during CRRT. The primary outcome is MAKE30, a composite of all-cause mortality, new or ongoing renal replacement therapy, or persistent renal dysfunction within 30 days after randomization. Secondary outcomes include filter lifespan, CRRT-free days, 30-day all-cause mortality, renal replacement therapy status, persistent renal dysfunction, ICU and hospital mortality, length of stay, CRRT duration, major bleeding, new bloodstream infection during ICU stay, SOFA score, number of filters used, and protocol-defined safety outcomes.

Conditions

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

Keywords

Nafamostat Mesylate; Continuous Renal Replacement Therapy (CRRT); Sepsis; Acute Kidney Injury (AKI); Randomized Clinical Trial (RCT)

Outcome Measures

Primary Outcomes (1)

• Major Adverse Kidney Events at Day 30 (MAKE30)

  MAKE30 is a composite endpoint defined as the occurrence of any of the following within 30 days after randomization: 1. All-cause death: the participant dies within 30 days after enrollment. If death has not occurred, proceed to the next criterion. 2. New initiation of or persistent need for renal replacement therapy: on Day 30 after enrollment, the participant still requires any form of renal replacement therapy, including CRRT, intermittent hemodialysis, sustained low-efficiency daily dialysis/continuous intermittent renal replacement therapy, peritoneal dialysis, and related modalities. Even if the participant had been temporarily weaned from therapy during the interval, the event is considered to have occurred if renal replacement therapy is still required on Day 30. If this criterion is not met, proceed to the next criterion. 3. Persistent renal dysfunction: on Day 30, the participant's serum creatinine level reaches or exceeds twice the baseline value.

  From randomization to day 30

Secondary Outcomes (14)

• Mean filter lifespan

  From first CRRT initiation to last CRRT discontinuation within 30 days after randomization

• CRRT-free days through Day 30

  From randomization to day 30

• All-cause mortality by Day 30

  From randomization to day 30

• New or Ongoing Renal Replacement Therapy

  Days 27-33 after randomization

• Persistent Renal Dysfunction at Day 30

  Day 30 after randomization

Other Outcomes (8)

• Metabolic acidosis

  From randomization to day 30

• Citrate toxicity

  From randomization to day 30

• Metabolic alkalosis

  From randomization to day 30

Study Arms (2)

Citrate group

ACTIVE COMPARATOR

Participants in this arm receive regional citrate anticoagulation during continuous renal replacement therapy (CRRT) according to standard institutional protocols. Citrate is infused pre-filter to maintain post-filter ionized calcium concentration between 0.2-0.4 mmol/L, with a maximum not exceeding 0.6 mmol/L. Calcium is replaced post-filter or systemically to maintain normal systemic ionized calcium (1.0-1.2 mmol/L). Anticoagulation targets and dose adjustments follow predefined operational guidelines. Citrate accumulation is monitored by total-to-ionized calcium ratio, and protocol modifications are applied for patients with liver dysfunction or metabolic complications.

Drug: Citrate anticoagulation

NM group

EXPERIMENTAL

Nafamostat mesylate is administered as a continuous pre-filter infusion at an initial dose of 50 mg/h, adjusted to maintain activated partial thromboplastin time (aPTT) or other regional anticoagulation parameters as specified in the protocol. Dose modifications are made based on filter lifespan and bleeding risk.

Drug: Nafamostat Mesylate

Interventions

Nafamostat Mesylate DRUG

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.

NM group

Citrate anticoagulation DRUG

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.

Citrate group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 90 years, inclusive, regardless of sex.
• Meets Sepsis 3.0 diagnostic criteria and develops acute kidney injury within 7 days after the diagnosis of sepsis.
• After adequate resuscitation, meets KDIGO 2012 stage 2 or stage 3 acute kidney injury criteria, including any of the following:
• Serum creatinine increased to more than 3 times baseline; or Serum creatinine ≥4.0 mg/dL \[353.6 μmol/L\]; or Urine output \<0.3 mL/kg/h for ≥24 hours; or Anuria, defined as extremely low or absent urine output, lasting ≥12 hours.
• Or has an indication for CRRT, including any of the following:
• Blood urea nitrogen \>150 mg/dL; or Serum potassium \>6 mmol/L; or pH \<7.15; or Organ edema and/or fluid overload in the setting of AKI that is refractory to diuretic therapy.
• Expected duration of CRRT treatment \>48 hours.
• Written informed consent obtained.

You may not qualify if:

• Requirement for therapeutic anticoagulation, such as pulmonary embolism or deep vein thrombosis.
• Contraindication to systemic anticoagulation.
• Hemolytic uremic syndrome or thrombotic thrombocytopenic purpura.
• Acute liver failure and/or shock with persistent severe lactic acidosis, defined as two consecutive measurements of pH \<7.2 lasting for more than 2 hours, with lactate \>72.1 mg/dL \[8 mmol/L\].
• Chronic kidney disease requiring long-term regular dialysis.
• Acute kidney injury caused by permanent bilateral renal artery occlusion or surgical injury.
• Acute kidney injury caused by glomerulonephritis, interstitial nephritis, or vasculitis.
• Known allergy to study drugs, including nafamostat mesylate, sodium citrate, or their excipients.
• Kidney transplantation within 1 year.
• Planning pregnancy in the near term, pregnancy, or lactation.
• HIV infection.
• Only adsorptive filters such as oXiris are available at study enrollment.
• Participation in another clinical trial within the previous 3 months.
• Judged by the investigator to be in a moribund state or unlikely to complete the study intervention and primary outcome assessment, including but not limited to expected death within 24 hours after enrollment, decision for do-not-resuscitate order or limitation/withdrawal of life-sustaining treatment, or planned abandonment of active treatment and self-discharge within 24 hours due to terminal disease or patient/family preference.
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for enrollment.

Sponsors & Collaborators

• Jianfeng Xie: lead
• Southeast University, China: collaborator

MeSH Terms

Conditions

Sepsis; Acute Kidney Injury

Interventions

nafamostat

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Yingzi Huang

  Zhongda Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiwen Zhang

CONTACT

+86 025-83262750; xiwen_zhang@126.com

Study Design

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

Study Record Dates

• First Submitted: March 29, 2026
• First Posted: April 8, 2026
• Study Start: June 10, 2026
• Primary Completion (Estimated): June 10, 2028
• Study Completion (Estimated): December 10, 2028
• Last Updated: June 3, 2026

Record last verified: 2026-06