Antithrombin Supplementation in ECMO
Study Details
Study Description
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 |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| 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 Names:
|
| 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 Names:
|
Outcome Measures
Primary Outcome Measures
- Amount of heparin [through study completion, an average of 10 days]
Heparin dosage to maintain aPTT ratio between 1.5-2
Secondary Outcome Measures
- Bleeding [through study completion, an average of 10 days]
Bleeding complications
- Adequacy of anticoagulation [through study completion, an average of 10 days]
Adequacy of anticoagulation, assessed through Anti-Xa levels
- thrombosis [through study completion, an average of 10 days]
Patient's or circuit thrombosis
- transfusions [through study completion, an average of 10 days]
Blood products transfusion requirements
Eligibility Criteria
Criteria
Inclusion Criteria:
- patients requiring veno-venous ECMO for severe respiratory failure.
Exclusion Criteria:
- patients with pre-existent heparin-induced thrombocytopenia
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
- Principal Investigator: Mauro Panigada, MD, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GATRA2016
- 2016-004534-23