Heparin Induced Thrombocytopenia (HIT) Clinical Trial
Official title:
Argatroban Versus Lepirudin in Critically Ill Patients - A Randomized Double-blind Trial
The purpose of this study is to test the hypotheses that argatroban significantly increases efficacy and safety of renal replacement therapy measured as life time of haemodialysis filters as compared to lepirudin
Critically ill patients are at increased risk to develop deep vein thrombosis due to
immobilisation and/or the underlying disease. Usually, heparin is used for anticoagulation
in these patients. However, a serious complication of heparin therapy is heparin-induced
thrombocytopenia type II (HIT). HIT is an immune-mediated syndrome caused by antibodies
directed against the heparin-PF4-complex, which bind to platelets via the Fc part, thereby
activating platelets causing aggregation and hypercoagulability. Thus, with HIT the risk of
thrombosis and organ damage paradoxically even increases during heparin administration. HIT
is associated with significant morbidity and mortality if unrecognized. Therefore, patients,
who develop thrombocytopenia and/or thrombosis during heparin therapy are suspicious for HIT
and have to receive alternative anticoagulants2.
The direct thrombin inhibitor lepirudin (Refludan®) is equally effective as heparin in
prevention of deep vein thrombosis and lung embolism3. The elimination half life of
lepirudin averages 60 min, but in renal failure it may increase up to 48 hours. Critically
ill patients often develop acute renal failure requiring continuous renal replacement
therapy. Thus, if lepirudin is used in these patients, intensive dose adjustment is
necessary to avoid accumulation and severe bleeding. In contrast, effective anticoagulation
is needed to prevent clot formation within the extracorporeal circuit, as clotting
substantially increases the patients´ risks and costs of therapy.
Argatroban (Argatra®), another direct thrombin inhibitor, has recently been shown to be safe
and effective in prevention of deep vein thrombosis in patients with HIT. Interestingly,
argatroban is eliminated by hepatic metabolism. Therefore, no initial dose adjustment is
necessary in patients with renal failure. Preliminary reports document the feasibility of
argatroban for anticoagulation during haemodialysis. Observational data in patients
undergoing continuous haemodialysis suggest that life time of filters during argatroban
anticoagulation is not limited due to clot formation. Thus, argatroban would be safer and
more effective than lepirudin in critically ill patients requiring continuous renal
replacement therapy.
Therefore, we propose a prospective randomized double-blinded trial to test the hypotheses
that argatroban significantly increases efficacy and safety of renal replacement therapy
measured as life time of haemodialysis filters as compared to lepirudin
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00456001 -
Heparin Induced Thrombocytopenia: Pharmacoeconomics
|
N/A |