Reduced anticoagulation targets in extracorporeal life support (RATE): study protocol for a randomized controlled trial

Abstract

Background Although life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT). However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome. Methods We will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2–2.5 times baseline aPTT, 1.5–2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months. Discussion We hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO. Trial registration ClinicalTrials.gov NCT04536272. Registered on 2 September 2020. Netherlands Trial Register NL7969

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study

“…In addition, previous studies have described an increased incidence of heparin-induced thrombocytopenia (HIT) when compared to similar patient groups [ 12 ]. Currently, studies evaluating the degree and type of anticoagulation during ECMO are being performed, adding information in finding the optimal balance among anticoagulation, hemorrhage, and possibly related thrombocytopenia [ 23 ].…”

Optimizing Anticoagulation for Venovenous Extracorporeal Membrane Oxygenation: Finding the Right Balance

“…In light of the weak association between heparin doses and plasma aPTT levels, future studies should expand on identifying optimum monitoring biomarkers and their corresponding targets. We hope that a current randomized clinical trial investigating low-molecular-weight heparin and unfractionated heparin with different anticoagulation targets will provide further guidance regarding some of these important questions ( 10 ). For establishing specific anticoagulation monitoring targets, dedicated prediction tools could help assess the risk for bleeding and thrombosis and could further contribute to personalized care ( 11 ).…”

There Will be Blood—But Maybe Less with Prostaglandin E1

“…Furthermore, a question remains about whether the next step should be a larger RCT in which PGE 1 is added to heparin, or one in which a lower dose of heparin (or even no heparin) in combination with PGE 1 is compared with the current dose of heparin. That decision is probably better made once the results of the ongoing multicenter Reduced Anticoagulation Targets in Extracorporeal Life Support (RATE) study, that compares low-dose heparin or LMWH with moderate dose heparin, are in hand ( 11 ).…”