Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial.

INTRODUCTION

Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and lepirudin in critically ill surgical patients.

METHODS

Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events.

RESULTS

We identified 66 patients with suspected heparin-induced thrombocytopenia, including 28 requiring renal replacement therapy. Mean filter lifetimes did not differ between groups (argatroban 32 ± 25 hours (n = 12) versus lepirudin 27 ± 21 hours (n = 16), mean difference 5 hours, 95% CI -13 to 23, P = 0.227). Among all 66 patients, relevant bleeding occurred in four argatroban- versus eleven lepirudin-patients (OR 3.9, 95% CI 1.1 to 14.0, P = 0.040). In the argatroban-group, three thromboembolic events occurred compared to two in the lepirudin group (OR 0.7, 95% CI 0.1 to 4.4, P = 0.639). The incidence of confirmed heparin-induced thrombocytopenia was 23% (n = 15) in our study population.

CONCLUSIONS

This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation.

TRIAL REGISTRATION

Clinical Trials.gov NCT00798525. Registered 25 November 2008.