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
|Condition or disease||Intervention/treatment||Phase|
|Extracorporeal Membrane Oxygenation||Drug: Antithrombin supplementation Drug: No antithrombin supplementation||Phase 2 Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||49 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
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
- Amount of heparin [ Time Frame: through study completion, an average of 10 days ]Heparin dosage to maintain aPTT ratio between 1.5-2
- Bleeding [ Time Frame: through study completion, an average of 10 days ]Bleeding complications
- Adequacy of anticoagulation [ Time Frame: through study completion, an average of 10 days ]Adequacy of anticoagulation, assessed through Anti-Xa levels
- thrombosis [ Time Frame: through study completion, an average of 10 days ]Patient's or circuit thrombosis
- transfusions [ Time Frame: through study completion, an average of 10 days ]Blood products transfusion requirements
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
|Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico|
|Milano, MI, Italy, 20122|
|Principal Investigator:||Mauro Panigada, MD||Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano|