Argatroban Versus Lepirudin in Critically Ill Patients
Information source: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Heparin Induced Thrombocytopenia (HIT)
Intervention: Argatroban (Drug); Lepirudin (Drug)
Phase: Phase 4
Status: Terminated
Sponsored by: Heinrich-Heine University, Duesseldorf Official(s) and/or principal investigator(s): Peter Kienbaum, MD, Principal Investigator, Affiliation: Uniklinik Düsseldorf, Klinik für Anästhesiologie
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 a maximum 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
Universitätsklinikum Düsseldorf Klinik für Anästhesiologie, Düsseldorf 40225, Germany
Additional Information
Starting date: January 2009
Last updated: June 20, 2012
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