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Argatroban Versus Lepirudin in Critically Ill Patients

Information source: Heinrich-Heine University, Duesseldorf
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Heparin Induced Thrombocytopenia (HIT)

Intervention: Argatroban (Drug); Lepirudin (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Heinrich-Heine University, Duesseldorf

Official(s) and/or principal investigator(s):
Peter Kienbaum, MD, Principal Investigator, Affiliation: Uniklinik Düsseldorf, Klinik für Anästhesiologie

Overall contact:
Peter Kienbaum, MD, Phone: ++49-211-81-16332, Email: Peter.Kienbaum@med.uni-duesseldorf.de

Summary

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

Clinical Details

Official title: Argatroban Versus Lepirudin in Critically Ill Patients - A Randomized Double-blind Trial

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Mean running time of two consecutive haemodialysis circuits

Secondary outcome: Incidence of bleeding, transfusion requirements, thromboembolic events, anaphylactic reactions, and SUSARs, length of hospital stay, mortality, time till target aPTT

Detailed description: 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

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Thrombocytopenia suspicious for HIT with decrease in platelet count >50% from

baseline obtained at hospital admission

- 4 T´s score for HIT probability >3 AND/OR positive ELISA for HIT

- Age ≥18 years

- Informed consent (if applicable)

Exclusion Criteria:

- Transient thrombocytopenia due to intraoperative bleeding

- Active bleeding

- Intracranial operations

- Liver dysfunction with spontaneous aPTT> 60 sec.

- History of adverse events or sensitivity against study drugs

- Pregnancy

- Age<18 years

- Preexisting psychiatric/neurologic disorders with long-term inability to provide

informed consent

Locations and Contacts

Peter Kienbaum, MD, Phone: ++49-211-81-16332, Email: Peter.Kienbaum@med.uni-duesseldorf.de

Universitätsklinikum Düsseldorf Klinik für Anästhesiologie, Düsseldorf 40225, Germany; Recruiting
Peter Kienbaum, PD Dr., Phone: +49 (0) 211- 8 11 81 00, Email: Peter.Kienbaum@med.uni-duesseldorf.de
Peter Kienbaum, PD Dr., Principal Investigator
Additional Information

Starting date: January 2009
Last updated: July 25, 2011

Page last updated: December 08, 2011

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