TEG Anticoagulation Monitoring During ECMO

NCT ID: NCT02271126

Last Updated: 2017-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-02
• Study Completion Date: 2016-11-30

Brief Summary

The best anticoagulation strategy during Extracorporeal Membrane Oxygenation (ECMO) is unknown. Actual recommendations suggest to use unfractionated heparin infusion and monitor the effect with either activated Partial Thromboplastin Time (aPTT) or Activated Clotting Time (ACT). Since hemorrhage is still the major adverse effect of ECMO with impact on mortality and morbidity, the investigators raised a question whether an alternative monitoring technique namely Thromboelastography (TEG) could allow a more accurate management of anticoagulation in this setting. To test this hypothesis the investigators designed a pilot study to test safety and feasibility of an anticoagulation monitoring algorithm based on TEG versus aPTT.

Detailed Description

Extracorporeal membrane oxygenation (ECMO) is frequently used as a supportive tool in the settings of acute severe respiratory and/or circulatory failure. The presence of the extracorporeal circuit and oxygenator bring along the need to anticoagulate the patients in order to prevent activation of the coagulation cascade that can lead to thrombosis of the artificial surfaces and losses of coagulation factors, fibrinogen and platelets. Despite tight monitoring with different anticoagulation essays bleeding remain the main threat for the patients on ECMO, leaving thrombosis as an anecdotic event.

In our institution, anticoagulation during ECMO is monitored mainly with aPTT ratio in a range of 1.5 to 2 (patient to normal). Recently, the investigators started to match Thromboelastography (TEG) assays to activated Partial Thromboplastin Time (aPTT) and Activated Clotting Time (ACT) routine measurements during ECMO. Data from a preliminary analysis of thirty-two patients show that in nearly half of TEG assays, the R (reaction time) parameter which is sensitive to inhibition of fibrin formation by heparin, was consistently prolonged despite aPTT and ACT were in the normal range. In the same patients the investigators registered high rate of bleeding (nearly 40% of patients suffered from clinically significant bleeding, i.e. bleeding that required heparin dose reduction, blood transfusions or interruption of the extracorporeal support). These findings suggests the possibility that the actual target of aPTT ratio might be overrated.

The purpose of this study is to test safety and feasibility of standardized protocol based on TEG versus current practice (aPTT) to manage anticoagulation during ECMO.

40 consecutive adults patients undergoing ECMO will be randomized in either the TEG-driven anticoagulation group or the aPTT-driven group. Written informed consent will be obtained according to national legislation.

In both groups, when the patient is connected to ECMO, an heparin bolus of 50-70 UI/kg (depending on baseline aPTT value) will be administered followed by a continuous infusion of 18 UI/kg/h started; for the first 12 hours thereafter proper anticoagulation level will be monitored with Activated Clotting Time (ACT, therapeutic range 180-210 seconds, performed every 1 or 2 hours according to the standardized protocol). From the thirteenth hour onwards each group will follow either aPTT monitoring or TEG according to randomization. Every morning in both groups aPTT, TEG, Antithrombin and anti-Factor Xa activity will be assessed.

• aPTT-driven group: aPTT ratio target is 1.5 - 2.0 as for actual clinical practice; frequency of aPTT measurements may vary from a minimum of 3 times per day to a maximum of 6 depending on the standardized protocol. When aPTT value falls well below the desired range an heparin bolus will be administered. When too high, infusion will be stopped for either 30 or 60 minutes.
• TEG-driven group: target range of R parameter at Kaolin activated-TEG (R K-TEG) is 16 - 24 minutes; frequency of TEG assays may vary from a minimum of 3 times per day to a maximum of 6 depending on the standardized protocol. When TEG value falls well below the desired range an heparin bolus will be administered, when is too high infusion will be stopped for either 30 or 60 minutes.

Daily management requires haemoglobin, platelets, PT ratio, D-dimer and fibrinogen to be checked 2 to 3 times daily, and maintained at specific values (Hb > 10 g/dl; PLT > 45.000/mm3; Fibrinogen > 150 mg/dl; Antithrombin activity > 70%; PT ratio > 1.5) with haemocomponents transfusion.

Data from each patient will be collected on a daily basis: laboratory exams, hemodynamic status, transfusions, surgery or invasive interventions, extracorporeal lung performance.

End of the study will be at ECMO discontinuation, after that deep vein thrombosis on patients' cannulation sites will be assessed with doppler ultrasound.

Conditions

Extracorporeal Membrane Oxygenation Complication

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

TEG

TEG-driven anticoagulation group: Anticoagulation will be monitored by TEG. Target will be a range of R parameter at Kaolin activated-TEG (R K-TEG) is 16 - 24 seconds; frequency of TEG assays may vary from a minimum of 3 times per day to a maximum of 6 depending on the standardized protocol. When TEG value falls well below the desired range an heparin bolus will be administered, when is too high infusion will be stopped for either 30 or 60 minutes.

Group Type: EXPERIMENTAL

TEG monitoring

Intervention Type: DEVICE

anticoagulation monitoring during ECMO will be according to TEG

Heparin

Intervention Type: DRUG

Anticoagulation provided to patients in ECMO

APTT

APTT-driven anticoagulation group: anticoagulation will be monitored by aPTT. aPTT ratio target is 1.5 - 2.0 as for actual clinical practice; frequency of aPTT measurements may vary from a minimum of 3 times per day to a maximum of 6 depending on the standardized protocol. When aPTT value falls well below the desired range an heparin bolus will be administered. When too high, infusion will be stopped for either 30 or 60 minutes.

Group Type: ACTIVE_COMPARATOR

APTT monitoring

Intervention Type: DEVICE

anticoagulation monitoring during ECMO will be according to aPTT

Heparin

Intervention Type: DRUG

Anticoagulation provided to patients in ECMO

Interventions

TEG monitoring

anticoagulation monitoring during ECMO will be according to TEG

Intervention Type: DEVICE

APTT monitoring

anticoagulation monitoring during ECMO will be according to aPTT

Intervention Type: DEVICE

Heparin

Anticoagulation provided to patients in ECMO

Intervention Type: DRUG

Other Intervention Names

Thromboelastography; activated Partial Thromboplastin Time

Eligibility Criteria

Inclusion Criteria

• All patients that initiate ECMO support for acute respiratory failure at our centre or by our equipe at another centre will be screened for eligibility.

Exclusion Criteria

• Patients under the age of 18, with proven Heparin-induced Thrombocytopenia or with a platelets count of less than 30.000/mm3 will be excluded from the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Mediterranean Institute for Transplantation and Advanced Specialized Therapies

OTHER

Sponsor Role: collaborator

Policlinico Hospital

OTHER

Sponsor Role: lead

Responsible Party

Mauro Panigada, MD

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mauro Panigada, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico

Locations

Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

Countries

Italy

References

Panigada M, E Iapichino G, Brioni M, Panarello G, Protti A, Grasselli G, Occhipinti G, Novembrino C, Consonni D, Arcadipane A, Gattinoni L, Pesenti A. Thromboelastography-based anticoagulation management during extracorporeal membrane oxygenation: a safety and feasibility pilot study. Ann Intensive Care. 2018 Jan 16;8(1):7. doi: 10.1186/s13613-017-0352-8.

Reference Type: DERIVED

PMID: 29340875 (View on PubMed)

Other Identifiers

932/2014

Identifier Type: -

Identifier Source: org_study_id