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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Filter Lifespan
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
None (Open Label)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age & Gender: Aged 18 to 80 years, regardless of gender.
- •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.
- •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
- •Platelet Count: Platelet count (PLT) ≥ 50 × 10⁹/L.
- •Body Mass Index (BMI): 18.5 kg/m² ≤ BMI ≤ 25 kg/m².
- •Informed Consent: Written informed consent obtained from the patient or their legally authorized representative.
排除标准
- •Hypersensitivity: Known allergy or hypersensitivity to Nafamostat Mesilate or any component of the formulation.
- •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).
- •Pregnancy/Lactation: Pregnant or breastfeeding women.
- •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.
- •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).
- •Severe Liver Dysfunction: Severe hepatic impairment (Child-Pugh Class C) or baseline total bilirubin levels exceeding 5 times the upper limit of normal.
- •Limited Life Expectancy: Expected survival time of less than 24 hours due to the progression of underlying disease.
- •Conflicting Trials: Current participation in another interventional clinical trial that may influence the outcomes of this study.
研究组 & 干预措施
Low-Dose Group
The patients are administered with continuous renal replacement therapy (CRRT) and standard critical care on the basis of routine treatment. If the patient has not received systemic anticoagulation before enrollment, the patient would be administered with a continuous intravenous infusion of Nafamostat Mesilate at an initial dose of 20 mg/h into the pre-filter port of the CRRT circuit. Meanwhile, the dose of Nafamostat should be titrated according to post-filter Activated Clotting Time (ACT) or Activated Partial Thromboplastin Time (APTT) to maintain the target anticoagulation level (post-filter ACT 150-250 s or APTT 50-70 s). Alternative anticoagulants or no anticoagulation could be administered to the patients if bleeding complications occur or if the target anticoagulation levels cannot be achieved safely, and the medication changes and dosage adjustments are recorded.
干预措施: Nafamostat Low-Dose Group (Drug)
High-Dose Group
The patients are administered with continuous renal replacement therapy (CRRT) and standard critical care on the basis of routine treatment. If the patient has not received systemic anticoagulation before enrollment, the patient would be administered with a continuous intravenous infusion of Nafamostat Mesilate at an initial dose of 50 mg/h into the pre-filter port of the CRRT circuit. Meanwhile, the dose of Nafamostat should be titrated according to post-filter Activated Clotting Time (ACT) or Activated Partial Thromboplastin Time (APTT) to maintain the target anticoagulation level (post-filter ACT 150-250 s or APTT 50-70 s). Alternative anticoagulants or no anticoagulation could be administered to the patients if bleeding complications occur or if the target anticoagulation levels cannot be achieved safely, and the medication changes and dosage adjustments are recorded.
干预措施: Nafamostat High-Dose Group (Drug)
结局指标
主要结局
Filter Lifespan
时间窗: 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.
次要结局
- Filter Transmembrane Pressure (TMP) Changes(From hour 0 (initiation of anticoagulation) to hour 72 (end of Day 3), with assessments at predefined hourly intervals.)
- Incidence of Filter Clotting Events(From baseline (initiation of CRRT) up to 72 hours post-baseline, or until filter replacement/discontinuation, whichever occurs first.)
- Duration of CRRT(From baseline (initiation of CRRT) up to 72 hours post-baseline, or until filter replacement/discontinuation, whichever occurs first.)
- Delivered CRRT Dose(From initiation of CRRT until filter replacement or discontinuation, up to a maximum of 72 hours per session.)
- 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).)
- 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).)
- 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).)
- 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.)
- Hemoglobin Level(Before medication, Day 1, Day 2, and Day 3 after medication.)
- Platelet Count(Before medication, Day 1, Day 2, and Day 3 after medication.)
- Incidence of Bleeding Complications(From baseline (initiation of CRRT) up to 72 hours post-baseline, or until filter replacement/discontinuation, whichever occurs first.)
- Adverse Drug Reactions Related to Nafamostat(From initiation of Nafamostat Mesilate up to 72 hours post-initiation.)
- 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.)
研究者
Liu Zhanguo
Director of the department of critical care medicine, Principal Investigator
Zhujiang Hospital