When Heparin Stopped for Anticoagulation During ECMO Decannulation

Study Overview
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Brief Summary
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Heparin (regular or unfractionated heparin, not low molecular weight heparin) is given as a bolus (50-100 units per kilogram) at the time of extracorporeal membrane oxygenation(ECMO) cannulation, and by continuous infusion during ECMO. Heparin infusion is regulated to keep the whole blood activated clotting time (ACT) or activated partial thromboplastin time (APTT) at a designated level (usually 1.5 times normal for the ACT or APTT measurement system). An elevated ACT or APTT is associated with high risks of early and late complications,such as bleeding,hematoma,pseudoaneurysm,and arterial-venous fistula. Extracorporeal life support organization(ELSO) make recommendation that the cannulas can be removed ideally after the heparin has been stopped for 30 to 60 minutes.However,the Chinese Thoracis Society recommends that heparin should not be discontinued immediately before ECMO decannulation, but gradually reduced within 24 hours, and then low molecular weight heparin is continued to be given for anticoagulation. Therefore,options of which time heparin stopped remain controversial.The investigators conduct this pilot study to investigate the opportunity of heparin stopped for anticoagulation before ECMO decannulation.

Detailed Description
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Forty adult patients with cardiac or respiratory failure supported by ECMO are enrolled in the study. Patients are randomly allocated to be treated with either a) heparin has been stopped for 1 hour before ECMO decannulation(regimen A), b) heparin gradually reduced within 24 hours after ECMO decannulation(regimen B).The investigators hypothesize that patients treated with regimen A as compared with patients treated with regimen B would decrease the incidence of complications during the ECMO decannulation period(from 1 hour before ECMO decannulation to 72 hours post decannulation).

Official Title
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A Randomized Controlled Pilot Trial of When Heparin Stopped for Anticoagulation During Extracorporeal Membrane Oxygenation Decannulation

Conditions
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Extracorporeal Membrane Oxygenation

Intervention / Treatment
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* Other: Heparin stopped before ECMO decannulation
* Other: Heparin reduced after ECMO decannulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECMO therapy was instituted to support circulatory and/or respiratory failure; Heparin continuous infusion for anticoagulation during ECMO; Native cardiac and pulmonary function improve,and the trial off is successful. Ensure each patient provides signed and dated informed consent. Exclusion Criteria: 1.History of thrombotic diseases or coagulation disorder； Thrombosis or bleeding events occurred prior to allocation； Heparin stopped prior to allocation； Other anticoagulants, antiplatelets, hemostatics and other drugs affected coagulation function have been used； The trial off has failed; Pregnant and lactating patients; Patients participated in the other studies; Patients couldn't accept comprehensive treatment; Patients couldn't acquire informed consent;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Previous<br>Heparin stopped before ECMO decannulation | Other: Heparin stopped before ECMO decannulation<br>* Heparin has been stopped for 1 hour before ECMO decannulation;The cannulas can be removed immediately with clots larger than 5 mm or enlarging clots in the circuit.<br>|
| Experimental: Afterwards<br>Heparin reduced after ECMO decannulation | Other: Heparin reduced after ECMO decannulation<br>* Heparin gradually reduced within 24 hours after ECMO decannulation, If excess bleeding occured,decrease the heparin infusion rapidly or turn the heparin off immediately. Protamine can be given to reversing heparin if necessary.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of bleeding and clotting complications |  | 72 hours after decannulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU mortality |  | 1 day after ICU discharge | 
| 28-days mortality |  | 28 days after decannulation | 
| Prothrombin time | Measured at the laboratory | 1 day and 3 days after decannulation | 
| Activated partial thromboplastin time | Measured at the laboratory | 1 day and 3 days after decannulation | 
| International normalised ratio | Measured at the laboratory | 1 day and 3 days after decannulation | 
| Fibrinogen | Measured at the laboratory | 1 day and 3 days after decannulation | 
| D-dimer | Measured at the laboratory | 1 day and 3 days after decannulation | 
| R time | Time to initial fibrin formation in minutes | 1 day and 3 days after decannulation | 
| K time | Minutes to 20 mm clot strength | 1 day and 3 days after decannulation | 
| α angle | Rate of clot strengthening | 1 day and 3 days after decannulation | 
| Maximum amplitude（MA） | MA represents the ultimate strength of the fibrin clot in mm | 1 day and 3 days after decannulation | 
| LY30 | Degree of clot lysis at 30 minutes | 1 day and 3 days after decannulation | 
| Volume of packed red cells transfusion |  | 3 days after decannulation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extracorporeal Membrane Oxygenation, Heparin, Anticoagulants, Decannulation, Randomized Controlled