Antithrombin Supplementation in ECMO

Policlinico Hospital

Status and phase: Completed; Phase 3; Phase 2

Conditions: Extracorporeal Membrane Oxygenation

Treatments: Drug: Antithrombin supplementation; Drug: No antithrombin supplementation

Study type: Interventional

Funder types: Other

Identifiers

NCT03208270

2016-004534-23 (EudraCT Number)

GATRA2016

Details and patient eligibility

About

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.

Full 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.

Enrollment: 49 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

• patients with pre-existent heparin-induced thrombocytopenia

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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49 participants in 2 patient groups

Antithrombin supplementation

Experimental group

Description:

Patients randomized to the study group will receive supplementation of antithrombin concentrate to maintain a functional antithrombin level between 80%-120%.

Treatment:

Drug: Antithrombin supplementation

No Antithrombin supplementation

Active Comparator group

Description:

Patients randomized to the control group will never receive supplementation of antithrombin unless "heparin resistance" occurs.

Treatment:

Drug: No antithrombin supplementation