Efficacy and Safety of Nafamostat Mesylate for VV-ECMO Anticoagulation

Efficacy and Safety of Nafamostat Mesylate for VV-ECMO Anticoagulation: a Randomized, Single-blind, Multicenter Exploratory, Heparin-controlled Trial

The purpose of this study was to compare the efficacy and safety of nafamostat mesylate and unfractionated heparin during ECMO anticoagulation in critically ill patients.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Anticoagulation
• Intervention / Treatment: Drug: Nafamostat Mesylate; Drug: Unfractionated Heparin

Detailed Description

During ECMO treatment, nafamostat mesylate and unfractionated heparin were randomly administered for continuous anticoagulation, respectively, and the incidence of bleeding and thrombotic complications during anticoagulation was compared between the two groups.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Wuhan Union Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged >= 18 and <= 80 years;
• Successfully established ECMO (VA/VV) treatment by percutaneous puncture due to cardiogenic shock or respiratory failure;
• Anticoagulation required during ECMO treatment; Before the establishment of ECMO, the APTT test value was within the normal range, and the platelets were not less than 80G/L;
• Within 48 hours of ECMO establishment, APTT test results were between 1 and 1.75 times the upper limit of normal, PLT>80 G/L, and no serious bleeding and thrombosis;
• Sign the informed consent.

Exclusion Criteria:

• Pregnant;
• Bleeding risk or active bleeding;
• Pre-existing diseases requiring long-term anticoagulation before ECMO: pulmonary embolism, deep vein thrombosis, intraventricular thrombosis, atrial fibrillation, etc.;
• Long-term use of anticoagulants before ECMO;
• Antiplatelet drugs were used before ECMO;
• Allergy to heparin, nafamostat mesylate;
• Repeated puncture at the same site for more than 3 times;
• Expected ECMO treatment time < 3 days;
• Patients with an expected survival period of less than 48 hours;
• Patients undergoing extracorporeal cardiopulmonary resuscitation;
• Burn patients; Blood purification treatment using polyacrylonitrile membrane filter;
• Heterozygous ECMO mode or ECMO therapy solely for CO2 removal;
• Other reasons that the investigator considers inappropriate for inclusion;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nafamostat Mesylate; VV-ECMO patients were given continuous anticoagulation with nafamostat mesylate, coagulation function was monitored every 6 hours, and APTT was maintained at 1-1.75 times the upper limit of normal detection until reaching the study endpoints, including 14 days after enrollment, 24 hours after withdrawal from ECMO, or any switch to ECMO mode during ECMO treatment.	Drug: Nafamostat Mesylate; ECMO patients were given continuous anticoagulation with nafamostat mesylate, coagulation function was monitored every 6 hours, and APTT was maintained at 1-1.75 times the upper limit of normal detection until reaching the study endpoints, including 14 days after enrollment, 24 hours after withdrawal from ECMO, or any switch to ECMO mode during ECMO treatment.
Active Comparator: Unfractionated Heparin; VV-ECMO patients were given continuous anticoagulation with unfractionated heparin, coagulation function was monitored every 6 hours, and APTT was maintained at 1-1.75 times the upper limit of normal detection until reaching the study endpoints, including 14 days after enrollment, 24 hours after withdrawal from ECMO, or any switch to ECMO mode during ECMO treatment.	Drug: Unfractionated Heparin; ECMO patients were given continuous anticoagulation with unfractionated heparin, coagulation function was monitored every 6 hours, and APTT was maintained at 1-1.75 times the upper limit of normal detection until reaching the study endpoints, including 14 days after enrollment, 24 hours after withdrawal from ECMO, or any switch to ECMO mode during ECMO treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of severe bleeding during ECMO	The ratio of the number of patients with severe bleeding complications to the total number of cases in each group.	Up to 14 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of thrombosis during ECMO	The ratio of the number of patients with thrombosis complication to the number of cases in each group.	Up to 14 days.
Bleeding-free days during ECMO	Days without bleeding complications	Up to 14 days.
Oxygenator replacement frequency	Oxygenator replacement frequency and average number of replacements per patient;	Up to 14 days.
The incidence of ECMO dysfunction	The ratio of the number of cases with ECMO dysfunction in each group to the total number of cases.	Up to 14 days.
The average amount of red, plasma, cryoprecipitate, fibrinogen, and platelets per person per ECMO day	Average blood transfusion volume per ECMO day, including red blood cells, plasma, cryoprecipitate, fibrinogen, and platelets.	Up to 14 days.
The compliance rate of APTT test results	The ratio of the number of APTT tests that met the requirements to the total number of APTT tests during ECMO.	Up to 14 days.
Case fatality rate within 28 days	After follow-up, the fatality rates of all enrolled patients in each group within 28 days of the study began.	Up to 28 days.
In-hospital mortality	The fatality rates of all enrolled patients in each group during hospitalization.	Through study completion, an average of 2 months.
Average length of ICU stay.	Average number of days in ICU for each group of patients.	Through study completion, an average of 2 months.
Average length of hospital stay	The mean of the total hospitalization days for each group of patients	Through study completion, an average of 2 months.

Collaborators and Investigators

• Sponsor: Xiaobo Yang, MD

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 11, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Anticoagulation; Extracorporeal Membrane Oxygenation; Unfractionated heparin; Nafamostat mesylate
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Immunosuppressive Agents; Immunologic Factors; Protease Inhibitors; Serine Proteinase Inhibitors; Anticoagulants; Trypsin Inhibitors; Complement Inactivating Agents; Heparin; Calcium heparin; Nafamostat
• Other Study ID Numbers: NMST20211022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No