Clinical trial NCT03208270: Antithrombin Supplementation in ECMO
Official title: Pilot Study of Antithrombin Supplementation During Extracorporeal Membrane Oxigenation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Extracorporeal Membrane Oxygenation
Lead sponsor: Policlinico Hospital
Sponsor class: OTHER
Collaborators: name: The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
First posted: 2017-07-05
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* patients with pre-existent heparin-induced thrombocytopenia

Primary outcomes:
measure: Amount of heparin
timeFrame: through study completion, an average of 10 days
Secondary outcomes:
measure: Bleeding
timeFrame: through study completion, an average of 10 days
measure: Adequacy of anticoagulation
timeFrame: through study completion, an average of 10 days
measure: thrombosis
timeFrame: through study completion, an average of 10 days
measure: transfusions
timeFrame: through study completion, an average of 10 days
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
state: MI
Study officials:
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Mauro Panigada, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Panigada M, Spinelli E, De Falco S, Consonni D, Novembrino C, Boscolo Anzoletti M, Panarello G, Occhipinti G, Dos Santos CC, Pesenti A, Arcadipane A, Grasselli G. The relationship between antithrombin administration and inflammation during veno-venous ECMO. Sci Rep. 2022 Aug 22;12(1):14284. doi: 10.1038/s41598-022-17227-7.
citation: Panigada M, Spinelli E, Cucino A, Cipriani E, De Falco S, Panarello G, Occhipinti G, Arcadipane A, Sales G, Fanelli V, Brazzi L, Novembrino C, Consonni D, Pesenti A, Grasselli G. Antithrombin supplementation during extracorporeal membrane oxygenation: study protocol for a pilot randomized clinical trial. Trials. 2019 Jun 11;20(1):349. doi: 10.1186/s13063-019-3386-4.