When Heparin Stopped for Anticoagulation During ECMO Decannulation

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

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.

Study Overview

• Status: Recruiting
• Conditions: Extracorporeal Membrane Oxygenation
• Intervention / Treatment: Other: Heparin stopped before ECMO decannulation; Other: Heparin reduced after ECMO decannulation

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Li yahui, Master; Phone Number: +8618530060930; Email: zdyxyliyahui@163.com
• Study Contact Backup: Name: Lu yanqiu, Doctor; Phone Number: +8613598862310; Email: luyanqiu815@126.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • General ICU of the second affiliated hospital of zhengzhou university
      • Contact: Liu xiaojun, Bachelor; Email: drliuxiaojun@163.com
      • Contact: Qi shaoyan, Master; Phone Number: +8613523500988; Email: qishaoyan1970@163.com
      • Principal Investigator: Li yahui
      • Sub-Investigator: Lu yanqiu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Previous; Heparin stopped before ECMO decannulation	Other: Heparin stopped before ECMO decannulation; 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.
EXPERIMENTAL: Afterwards; Heparin reduced after ECMO decannulation	Other: Heparin reduced after ECMO decannulation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Zhengzhou University
• Investigators: Principal Investigator: Li yahui, Master, Second Affiliated Hospital of Zhengzhou University

Publications and helpful links

General Publications

• Tonna JE, Abrams D, Brodie D, Greenwood JC, Rubio Mateo-Sidron JA, Usman A, Fan E. Management of Adult Patients Supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO). ASAIO J. 2021 Jun 1;67(6):601-610. doi: 10.1097/MAT.0000000000001432.

Helpful Links

• The chinese thoracis society recommended that heparin should not be discontinued immediately before ECMO decannulation

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 15, 2022
• Primary Completion (ANTICIPATED): October 1, 2023
• Study Completion (ANTICIPATED): October 1, 2023

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: February 13, 2022
• First Posted (ACTUAL): February 15, 2022

Study Record Updates

• Last Update Posted (ACTUAL): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 11, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Heparin; Anticoagulants; Extracorporeal Membrane Oxygenation; Decannulation; Randomized Controlled
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: LHGJ20210421

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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