Continuous Renal Replacement Therapy (CRRT)
Conditions
Keywords
Continuous Renal Replacement Therapy (CRRT), Anticoagulation Efficacy, Nafamostat Mesilate (NM)
Brief summary
This is a single-center, randomized, open-label, parallel-controlled clinical trial designed to investigate the anticoagulation efficacy and safety of different initial doses of Nafamostat Mesilate (NM) in ICU patients undergoing Continuous Renal Replacement Therapy (CRRT). Researchers will screen patients admitted to the Department of Critical Care Medicine at Zhujiang Hospital, Southern Medical University, to identify eligible participants based on inclusion and exclusion criteria. After obtaining informed consent, participants will be randomized into two groups. On the basis of standardized CRRT treatment, the Low-Dose Group (Group A) will receive a continuous infusion of Nafamostat Mesilate at an initial dose of 20 mg/h, while the High-Dose Group (Group B) will receive an initial dose of 50 mg/h. The drug will be continuously infused pre-filter into the CRRT circuit. Dosage adjustments will be made for both groups to maintain target anticoagulation levels while ensuring that pre-filter safety limits are not exceeded. The primary outcome measure is filter lifespan, along with other secondary outcomes.
Detailed description
Investigational drug: Nafamostat Mesilate for Injection Study title: Comparison of Anticoagulation Efficacy of Different Doses of Nafamostat Mesilate during Continuous Renal Replacement Therapy in ICU: A Single-Center, Randomized, Open-Label, Parallel-Controlled Clinical Trial Principal Investigator: Zhanguo Liu, Professor, Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University Study subjects: Patients aged 18-80 years admitted to the ICU requiring Continuous Renal Replacement Therapy (CRRT) for ≥24 hours, with normal coagulation function (INR ≤1.5, Fibrinogen ≥1.5 g/L, APTT ≤45 s), platelet count ≥50 G/L, and BMI between 18.5 and 25 kg/m². Patients with known allergy to Nafamostat, active bleeding, pregnancy, or those using other systemic anticoagulants or extracorporeal devices (e.g., ECMO, IABP) are excluded. Study objectives: The primary objective is to determine whether a high initial dose (50 mg/h) of Nafamostat Mesilate, compared to a low initial dose (20 mg/h), prolongs the filter lifespan in ICU patients undergoing CRRT. Secondary objectives include evaluating differences in transmembrane pressure, clotting events, CRRT duration, blood flow rates, delivered dose, and safety outcomes such as bleeding complications and adverse drug reactions. Study design: A single-center, randomized, open-label, parallel-controlled clinical trial. Method: Eligible patients will be randomized into two groups:Low-Dose Group (Group A): Receives Nafamostat Mesilate at an initial continuous infusion dose of 20 mg/h pre-filter.High-Dose Group (Group B): Receives Nafamostat Mesilate at an initial continuous infusion dose of 50 mg/h pre-filter. In both groups, the dosage will be titrated in increments of 5 or 10 mg/h based on activated clotting time (ACT) and activated partial thromboplastin time (APTT) measured post-filter. The target is to maintain post-filter ACT at 150-250 s (or 2.5 times baseline) and APTT at 50-70 s, while ensuring pre-filter values do not exceed 1.5 times baseline. The intervention continues until CRRT discontinuation due to filter clotting, recovery, transfer, death, or bleeding. Standardized CRRT protocols (CVVH mode, blood flow 150-200 mL/min) and routine critical care treatments are applied to all patients. Course: Up to 72 hours per filter session, or until CRRT discontinuation. Sample size: 92 patients (46 per group). The number of study centers: 1 Study center:Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China Primary endpoint:Filter Lifespan: Defined as the duration (in hours) from the initiation of Nafamostat anticoagulation to filter change or discontinuation of CRRT due to clotting, extended downtime, renal recovery, patient transfer/death, or bleeding events necessitating a change in anticoagulation strategy. Secondary endpoints:Filter Performance: Changes in Transmembrane Pressure (TMP) at specified intervals (2h, 8h, 16h, 24h, etc.); Number of filter clotting events (defined as TMP \>250 mmHg or visible clotting). Treatment Metrics: Total CRRT duration; Average daily blood flow rate; Daily delivered CRRT dose. Coagulation Parameters: Maintenance levels of ACT and APTT; Changes in hemoglobin and platelet counts. Safety Outcomes: Incidence of bleeding complications (e.g., gingival bleeding, epistaxis, GI bleeding); Incidence of adverse drug reactions related to Nafamostat (e.g., rash, hyperkalemia, elevated liver enzymes, gastrointestinal symptoms); Total blood product transfusion volume during CRRT. Safety endpoints:Adverse Events: Monitoring for specific adverse reactions including drug allergy (rash), hyperkalemia, elevated AST/ALT, bleeding, thrombocytopenia, and gastrointestinal symptoms (nausea, vomiting, diarrhea). Serious Adverse Events (SAE): Recording any event leading to death, life-threatening conditions, prolonged hospitalization, or significant disability, assessed for causality with the study drug.
Interventions
DRUGNafamostat Low-Dose Group
Nafamostat Mesilate will be reconstituted using 5% Glucose Injection. For complete dissolution, at least 1 mL of solvent is added to the 10 mg vial, or at least 5 mL is added to the 50 mg vial. The resulting solution will be administered via continuous infusion into the CRRT circuit pre-filter (infused through a three-way stopcock connected to the blood inlet line of the dialysis circuit) at a maintained rate of 20 mg/h
DRUGNafamostat High-Dose Group
Nafamostat Mesilate will be reconstituted using 5% Glucose Injection. For complete dissolution, at least 1 mL of solvent is added to the 10 mg vial, or at least 5 mL is added to the 50 mg vial. The resulting solution will be administered via continuous infusion into the CRRT circuit pre-filter (infused through a three-way stopcock connected to the blood inlet line of the dialysis circuit) at a maintained rate of 50 mg/h
Sponsors
Zhujiang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open Label)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Filter Lifespan | From the initiation of Nafamostat Mesilate anticoagulation until filterreplacement or discontinuation of CRRT (up to 72 hours per filter session). | Defined as the duration (in hours) from the initiation of Nafamostat Mesilate anticoagulation in the CRRT circuit to the discontinuation of Nafamostat anticoagulation due to any of the following reasons: (i) Filter replacement; (ii) Termination of CRRT due to: filter clotting, prolonged filter downtime, renal recovery, patient transfer out of the ICU, or death; (iii) Discontinuation of Nafamostat anticoagulation due to adverse events such as bleeding, necessitating a change in the anticoagulation strategy. Data Source: Nursing records and medical charts. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Filter Transmembrane Pressure (TMP) Changes | From hour 0 (initiation of anticoagulation) to hour 72 (end of Day 3), with assessments at predefined hourly intervals. | TMP of the CRRT filter will be measured at the following time points after initiation of Nafamostat Mesilate anticoagulation: * Day 1: 2hours, 8hours, 16hours, 24hours * Day 2: 8hours, 16hours, 24hours (equivalent to 32hours, 40hours, 48hours from start) * Day 3: 8hours, 16hours, 24hours (equivalent to 56hours, 64hours, 72hours from start) Data obtained from nursing records and medical charts. |
| Incidence of Filter Clotting Events | From baseline (initiation of CRRT) up to 72 hours post-baseline, or until filter replacement/discontinuation, whichever occurs first. | Defined as Transmembrane Pressure (TMP) exceeding 250 mmHg and/or visible clotting in the air collection chamber. Data obtained from nursing records and medical charts. |
| Duration of CRRT | From baseline (initiation of CRRT) up to 72 hours post-baseline, or until filter replacement/discontinuation, whichever occurs first. | The total duration of the CRRT treatment session. Data obtained from nursing records and medical charts. |
| Delivered CRRT Dose | From initiation of CRRT until filter replacement or discontinuation, up to a maximum of 72 hours per session. | The actual delivered dose of CRRT treatment. Data obtained from nursing records and medical charts. |
| Activated Partial Thromboplastin Time (APTT) | At baseline (before CRRT), 2 hours post-baseline, 8 hours post-baseline, and at the last available measurement during treatment (up to 72 hours post-baseline). | APTT measured from peripheral venous blood. Data obtained from laboratory test results. |
| Prothrombin Time (PT) | At baseline (before CRRT), 2 hours post-baseline, 8 hours post-baseline, and at the last available measurement during treatment (up to 72 hours post-baseline). | PT measured from peripheral venous blood. Data obtained from laboratory test results. |
| Fibrinogen (FIB) | At baseline (before CRRT), 2 hours post-baseline, 8 hours post-baseline, and at the last available measurement during treatment (up to 72 hours post-baseline). | FIB measured from peripheral venous blood. Data obtained from laboratory test results. |
| Activated Clotting Time (ACT) | Pre-medication baseline, followed by assessments at 2hours, 8hours, 16hours, 24hours, 32hours, 40hours, 48hours, 56hours, 64hours, and 72hours post-initiation of anticoagulation. | ACT levels indicating systemic coagulation status and CRRT anticoagulation effect. Data obtained from laboratory test results. |
| Hemoglobin Level | Before medication, Day 1, Day 2, and Day 3 after medication. | Hemoglobin concentration measured from peripheral venous blood to assess anemia and guide transfusion timing during CRRT. Data obtained from laboratory test results. |
| Platelet Count | Before medication, Day 1, Day 2, and Day 3 after medication. | Platelet count measured from peripheral venous blood to assess bleeding risk and monitor thrombocytopenia during CRRT. Data obtained from laboratory test results. |
| Incidence of Bleeding Complications | From baseline (initiation of CRRT) up to 72 hours post-baseline, or until filter replacement/discontinuation, whichever occurs first. | Observation of bleeding manifestations such as gingival bleeding, epistaxis, skin ecchymosis, and gastrointestinal bleeding during CRRT. Data obtained from physician reports, nursing documents, and medical charts. |
| Adverse Drug Reactions Related to Nafamostat | From initiation of Nafamostat Mesilate up to 72 hours post-initiation. | Includes drug allergy (rash), hyperkalemia, elevated AST/ALT, bleeding, decreased platelets, and gastrointestinal symptoms (nausea, vomiting, diarrhea). Data obtained from physician reports, nursing documents, and medical charts. |
| Blood Transfusion Volume During Nafamostat-Anticoagulated CRRT | From baseline (initiation of CRRT) up to 72 hours post-baseline, or until filter replacement/discontinuation, whichever occurs first. | Total volume of blood or blood components (e.g., red blood cells, platelets, fresh frozen plasma, cryoprecipitate) transfused during the CRRT treatment period with Nafamostat anticoagulation. Data obtained from physician reports, nursing documents, and medical charts. |
Countries
China
Contacts
CONTACTZhanguo Liu, M.D.PhD
PRINCIPAL_INVESTIGATORZhanguo Liu, M.D.PhD
Department of Critical Care Medicine of Zhujiang Hospital
Outcome results
None listed