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Antithrombin Supplementation in ECMO

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ClinicalTrials.gov Identifier: NCT03208270
Recruitment Status : Completed
First Posted : July 5, 2017
Last Update Posted : May 17, 2019
Sponsor:
Collaborator:
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
Information provided by (Responsible Party):
Mauro Panigada, MD, Policlinico Hospital

Brief Summary:
Bleeding is the most feared complication during extracorporeal membrane oxygenation (ECMO) and is associated with high dosing of heparin. There is no consensus on antithrombin (AT) supplementation during ECMO. However, AT is needed by heparin to properly anticoagulate. We hypothesize that maintaining normal antithrombin levels during ECMO is associated with a less heparin dosing and more adequate level of anticoagulation.

Condition or disease Intervention/treatment Phase
Extracorporeal Membrane Oxygenation Drug: Antithrombin supplementation Drug: No antithrombin supplementation Phase 2 Phase 3

Detailed Description:

Extracorporeal membrane oxygenation (ECMO) is a life support for patients with severe acute respiratory failure when conventional treatments failed but it is accompanied by a significant risk of bleeding. Heparin is required during ECMO to avoid circuit thrombosis and its anticoagulant effect is strictly dependent on antithrombin (AT). AT also plays a central role in mediating inflammation. Acquired AT deficiency is common in patients on ECMO, arguably due to long term anticoagulation in addition to sepsis itself. Guidelines suggest to supplement AT in ECMO only when its deficiency coexists with heparin resistance. Few studies evaluated the effect of AT supplementation during ECMO without a consensus on the appropriate level to be maintained. AT supplementation increase anti-Factor Xa (anti-Xa) levels without increasing heparin dosage. This may have a clinical impact because risk of bleeding during ECMO is associated with higher heparin dosage.

We hypothesize that maintaining normal antithrombin activity levels (80%-120%) during ECMO is associated with: I. less heparin dosage, II. a more adequate level of anticoagulation, III. less hemostasis related complications, and IV. a lower level of inflammation.

Adult patients on veno-venous ECMO for respiratory failure will be randomized to maintain AT between 80% and 100% (study group) or no supplementation unless heparin resistance occurs (control group). Sample size of at least 20 patients per group (n=40) is calculated upon the primary outcome measure of reduction of heparin use in the study group compared to the control group. AT and anti-Xa will be measured before ECMO and daily while on ECMO. Anticoagulation will be guaranteed with unfractionated heparin infusion with a target aPTT 1.5-2X normal. Study will end at ECMO removal.

Consistent literature suggests that current ECMO anticoagulation strategies are suboptimal probably due to improper antithrombin supplementation. A normal antithrombin level could guarantee an adequate anticoagulation regimen.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Pilot Study of Antithrombin Supplementation During Extracorporeal Membrane Oxigenation
Actual Study Start Date : July 28, 2017
Actual Primary Completion Date : May 15, 2019
Actual Study Completion Date : May 15, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arm Intervention/treatment
Experimental: Antithrombin supplementation
Patients randomized to the study group will receive supplementation of antithrombin concentrate to maintain a functional antithrombin level between 80%-120%.
Drug: Antithrombin supplementation
antithrombin concentrate will be supplemented to maintain a functional antithrombin level between 80%-120%
Other Name: Antithtrombin

Active Comparator: No Antithrombin supplementation
Patients randomized to the control group will never receive supplementation of antithrombin unless "heparin resistance" occurs.
Drug: No antithrombin supplementation
supplementation of antithrombin will not be provided unless "heparin resistance" occurs
Other Name: No antithrombin




Primary Outcome Measures :
  1. Amount of heparin [ Time Frame: through study completion, an average of 10 days ]
    Heparin dosage to maintain aPTT ratio between 1.5-2


Secondary Outcome Measures :
  1. Bleeding [ Time Frame: through study completion, an average of 10 days ]
    Bleeding complications

  2. Adequacy of anticoagulation [ Time Frame: through study completion, an average of 10 days ]
    Adequacy of anticoagulation, assessed through Anti-Xa levels

  3. thrombosis [ Time Frame: through study completion, an average of 10 days ]
    Patient's or circuit thrombosis

  4. transfusions [ Time Frame: through study completion, an average of 10 days ]
    Blood products transfusion requirements



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients requiring veno-venous ECMO for severe respiratory failure.

Exclusion Criteria:

  • patients with pre-existent heparin-induced thrombocytopenia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03208270


Locations
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Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milano, MI, Italy, 20122
Sponsors and Collaborators
Policlinico Hospital
The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
Investigators
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Principal Investigator: Mauro Panigada, MD Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Mauro Panigada, MD, MD, Policlinico Hospital
ClinicalTrials.gov Identifier: NCT03208270    
Other Study ID Numbers: GATRA2016
2016-004534-23 ( EudraCT Number )
First Posted: July 5, 2017    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Antithrombins
Antithrombin III
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants