Antithrombin Supplementation in ECMO

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Pilot Study of Antithrombin Supplementation During Extracorporeal Membrane Oxigenation

Conditions
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Extracorporeal Membrane Oxygenation

Intervention / Treatment
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* Drug: Antithrombin supplementation
* Drug: No antithrombin supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients requiring veno-venous ECMO for severe respiratory failure. Exclusion Criteria: patients with pre-existent heparin-induced thrombocytopenia

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antithrombin supplementation<br>Patients randomized to the study group will receive supplementation of antithrombin concentrate to maintain a functional antithrombin level between 80%-120%. | Drug: Antithrombin supplementation<br>* antithrombin concentrate will be supplemented to maintain a functional antithrombin level between 80%-120%<br>* Other names: Antithtrombin;|
| Active Comparator: No Antithrombin supplementation<br>Patients randomized to the control group will never receive supplementation of antithrombin unless heparin resistance occurs. | Drug: No antithrombin supplementation<br>* supplementation of antithrombin will not be provided unless heparin resistance occurs<br>* Other names: No antithrombin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of heparin | Heparin dosage to maintain aPTT ratio between 1.5-2 | through study completion, an average of 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding | Bleeding complications | through study completion, an average of 10 days | 
| Adequacy of anticoagulation | Adequacy of anticoagulation, assessed through Anti-Xa levels | through study completion, an average of 10 days | 
| thrombosis | Patient's or circuit thrombosis | through study completion, an average of 10 days | 
| transfusions | Blood products transfusion requirements | through study completion, an average of 10 days |