Low- versus high-dose nafamostat for anticoagulation during CRRT in ICU patients

Comparison of Anticoagulant Effects of Different Doses of Nafamostat in Continuous Renal Replacement Therapy (CRRT) in the Intensive Care Unit (ICU): A Single-Center, Randomized, Open-Label, Parallel-Controlled Clinical Trial

This study tests whether starting nafamostat at 50 mg/h rather than 20 mg/h keeps CRRT filters from clotting longer in adult ICU patients on continuous renal replacement therapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 92 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Zhujiang Hospital (other)
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07469072 on ClinicalTrials.gov

What this trial studies

This single-center, randomized, open-label trial will enroll adult ICU patients at Zhujiang Hospital who require CRRT for at least 24 hours and meet predefined coagulation and laboratory criteria. Participants are randomized to continuous pre-filter infusion of nafamostat mesilate at an initial dose of 20 mg/h (low-dose) or 50 mg/h (high-dose), with dose adjustments as needed to maintain target anticoagulation. The primary outcome is filter lifespan, and secondary outcomes include transmembrane pressure, circuit clotting events, delivered dialysis dose, CRRT duration, and safety outcomes such as bleeding and adverse drug reactions. Key exclusions include active bleeding, known nafamostat allergy, concurrent systemic anticoagulants or extracorporeal devices, pregnancy, and BMI or lab values outside specified ranges.

Who should consider this trial

Good fit: Adults aged 18–80 in the ICU who need CRRT for ≥24 hours, have normal coagulation tests (INR ≤1.5, APTT ≤45 s, fibrinogen ≥1.5 g/L), platelets ≥50×10⁹/L, and BMI 18.5–25 kg/m² are eligible candidates.

Not a fit: Patients with active bleeding, known hypersensitivity to nafamostat, concurrent use of other systemic anticoagulants or extracorporeal devices (e.g., ECMO), pregnancy, or those outside the specified BMI or laboratory ranges are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could identify a starting nafamostat dose that reduces filter clotting and decreases CRRT interruptions for ICU patients.

How similar studies have performed: Nafamostat is used in clinical practice and small observational studies support its role for CRRT anticoagulation, but randomized dose-comparison evidence is limited.

Eligibility criteria

Inclusion Criteria:

1. Age \& Gender: Aged 18 to 80 years, regardless of gender.
2. Clinical Indication: Admitted to the Intensive Care Unit (ICU) with a confirmed indication for Continuous Renal Replacement Therapy (CRRT) and an expected treatment duration of greater than 24 hours.
3. Coagulation Status: Normal coagulation function prior to CRRT initiation, defined as:International Normalized Ratio (INR) ≤ 1.5,Fibrinogen (FIB) ≥ 1.5 g/L,Activated Partial Thromboplastin Time (APTT) ≤ 45 seconds
4. Platelet Count: Platelet count (PLT) ≥ 50 × 10⁹/L.
5. Body Mass Index (BMI): 18.5 kg/m² ≤ BMI ≤ 25 kg/m².
6. Informed Consent: Written informed consent obtained from the patient or their legally authorized representative.

Exclusion Criteria:

1. Hypersensitivity: Known allergy or hypersensitivity to Nafamostat Mesilate or any component of the formulation.
2. Active Bleeding: Presence of active bleeding or a high risk of bleeding that contraindicates anticoagulation (e.g., active gastrointestinal bleeding, intracranial hemorrhage, or recent major surgery with a high bleeding risk).
3. Pregnancy/Lactation: Pregnant or breastfeeding women.
4. Concurrent Anticoagulation: Current use of other systemic anticoagulants (e.g., unfractionated heparin, low molecular weight heparin, warfarin, or direct oral anticoagulants) that cannot be discontinued.
5. Concurrent Extracorporeal Support: Concurrent use of other extracorporeal life support or blood purification therapies that may interfere with coagulation assessment, such as Extracorporeal Membrane Oxygenation (ECMO), Intra-Aortic Balloon Pump (IABP), or Plasma Exchange (PE).
6. Severe Liver Dysfunction: Severe hepatic impairment (Child-Pugh Class C) or baseline total bilirubin levels exceeding 5 times the upper limit of normal.
7. Limited Life Expectancy: Expected survival time of less than 24 hours due to the progression of underlying disease.
8. Conflicting Trials: Current participation in another interventional clinical trial that may influence the outcomes of this study.

Where this trial is running

Guangzhou, Guangdong

• Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Zhanguo Liu, M.D.PhD — Department of Critical Care Medicine of Zhujiang Hospital
• Study coordinator: Zhanguo Liu, M.D.PhD

Conditions: Continuous Renal Replacement Therapy, Anticoagulation Efficacy, Nafamostat Mesilate