Comparison of Anticoagulant Effects of Different Doses of Nafamostat in Continuous Renal Replacement Therapy (CRRT) in the Intensive Care Unit (ICU)
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Простыми словами
Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.
- Что изучают
- В протоколе указаны: Nafamostat Low-Dose Group, Nafamostat High-Dose Group.
- Кому может быть актуально
- Состояния в реестре: Continuous Renal Replacement Therapy (CRRT). Базовые параметры: 18 лет — 80 лет · Все.
- Что важно проверить
- Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
- Где проводится
- Китай
- Следующий шаг
- Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →
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Официальное название
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
Обзор
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.
Подробное описание
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.
Вмешательства
- Препарат Nafamostat 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 - Препарат Nafamostat 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
Первичные конечные точки
- Filter Lifespan [Срок оценки: From the initiation of Nafamostat Mesilate anticoagulation until filterreplacement or discontinuation of CRRT (up to 72 hours per filter session).]
Вторичные конечные точки (12)
- Filter Transmembrane Pressure (TMP) Changes [Срок оценки: From hour 0 (initiation of anticoagulation) to hour 72 (end of Day 3), with assessments at predefined hourly intervals.]
- Incidence of Filter Clotting Events [Срок оценки: From baseline (initiation of CRRT) up to 72 hours post-baseline, or until filter replacement/discontinuation, whichever occurs first.]
- Duration of CRRT [Срок оценки: From baseline (initiation of CRRT) up to 72 hours post-baseline, or until filter replacement/discontinuation, whichever occurs first.]
- Delivered CRRT Dose [Срок оценки: From initiation of CRRT until filter replacement or discontinuation, up to a maximum of 72 hours per session.]
- Activated Partial Thromboplastin Time (APTT) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: Pre-medication baseline, followed by assessments at 2hours, 8hours, 16hours, 24hours, 32hours, 40hours, 48hours, 56hours, 64hours, and 72hours post-initiation of anticoagulation.]
- Hemoglobin Level [Срок оценки: Before medication, Day 1, Day 2, and Day 3 after medication.]
- Platelet Count [Срок оценки: Before medication, Day 1, Day 2, and Day 3 after medication.]
- Incidence of Bleeding Complications [Срок оценки: 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 [Срок оценки: From initiation of Nafamostat Mesilate up to 72 hours post-initiation.]
Критерии участия
Критерии включения
- 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.
Критерии исключения
- 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.
Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.
Здоровые добровольцы: Нет
Дизайн исследования
- Распределение
- Рандомизированное
- Модель
- Параллельные группы
- Маскирование
- Открытое
- Основная цель
- Лечение
Центры проведения
Китай · 1 центр
- Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University — Гуанчжоу
Идентификаторы
NCT: NCT07469072 · 2025-KY-539-01