Heparin Induced Thrombocytopenia (HIT)Phase 4ALiCiaNCT00798525
Argatroban Versus Lepirudin in Critically Ill Patients
A Phase 4 study testing Argatroban and Lepirudin in people with Heparin Induced Thrombocytopenia (HIT), run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heparin Induced Thrombocytopenia (HIT)
- What is being tested?
- Argatroban and Lepirudin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2009to Mar 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Universitätsklinikum Düsseldorf Klinik für Anästhesiologie
Düsseldorf, 40225
About this study
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
Read the 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
- Conditions
- Heparin Induced Thrombocytopenia (HIT)
- Being tested
- Argatroban, Lepirudin
- Keywords
- thrombocytopenia, Heparin, Lepirudin, Argatroban, critically ill patients
- Medical subject headings
- Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArgatrobanDrug
Also called Argatra®, MA number: 62085.00.0
Argatra (Argatroban) will be diluted to 0.6 mg/ml and 0.5 µg/kg/min will be administered continuously in patients without liver disfunction. In patients with liver disfunction, defined by a bilirubin of > 4mg/dl, argatroban will be administered as a continuous infusion of 0,25 µg/kg/min with a final concentration of 0,3 mg/ml.
LepirudinDrug
Also called Refludan®, MA number: EU/1/97/035/003
Refludan (Lepirudin) will be diluted to a final concentration of 0.1mg/ml and initiated as a continuous infusion of 5µg/kg/h in patients with continuous renal replacement therapy. In patients with moderate renal impairment (Creatinine ≥1,3 mg/dl) a final concentration 0,2 mg/ml of will be used to provide continuous infusion of 10 µg/kg/h. Patients without renal impairment (Creatinine < 1,3 mg/dl) will receive a continuous infusion of 50 µg/kg/h by a final concentration of 1 mg/ml of Lepirudin.
| Study group | Role | What they receive |
|---|---|---|
| PR1 | Active comparator | Patients treated with Argatroban (Argatra®), a direct thrombin inhibitor Receives: Drug: Argatroban |
| PR2 | Active comparator | Patients treated with Lepirudin (Refludan®), a direct thrombin inhibitor Receives: Drug: Lepirudin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean running time of a maximum of two consecutive haemodialysis circuits
Measured: seven days starting at time of HIT suspicion
Secondary outcomes (1)
Incidence of bleeding, transfusion requirements, thromboembolic events, anaphylactic reactions, and SUSARs, length of hospital stay, mortality, time till target aPTT
Measured: seven days starting at time of HIT suspicion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2008 (estimated)
- Study startJan 2009
- Primary completionMar 2012
- Study completionMar 2012
Why it stopped: Supply of Lepirudin ended on 01. April 2012, thus trial terminated on 31. March 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Heparin Induced Thrombocytopenia (HIT)Studies of the same condition, open and under way.
- More trials run by Heinrich-Heine University, DuesseldorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heinrich-Heine University, Duesseldorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Kienbaum, MD, Principal investigator, Uniklinik Düsseldorf, Klinik für Anästhesiologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00798525
- Sponsor's protocol ID
- 2006-003122-28
- Acronym
- ALiCia
- Status last verified
- Jun 2012
- First submitted
- 25 Nov 2008
- Last updated
- 21 Jun 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tsujimoto H, Tsujimoto Y, Nakata Y, Fujii T, Takahashi S, Akazawa M, Kataoka Y. Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2020 Dec 14;12(12):CD012467. doi: 10.1002/14651858.CD012467.pub3.
PubMed 33314078Beiderlinden M, Werner P, Bahlmann A, Kemper J, Brezina T, Schafer M, Gorlinger K, Seidel H, Kienbaum P, Treschan TA. Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry - a prospectively controlled randomized double-blind clinical trial. BMC Anesthesiol. 2018 Feb 9;18(1):18. doi: 10.1186/s12871-018-0475-y.
PubMed 29426286Treschan TA, Schaefer MS, Geib J, Bahlmann A, Brezina T, Werner P, Golla E, Greinacher A, Pannen B, Kindgen-Milles D, Kienbaum P, Beiderlinden M. Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial. Crit Care. 2014 Oct 25;18(5):588. doi: 10.1186/s13054-014-0588-8.
PubMed 25344113
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Argatroban Versus Lepirudin in Critically Ill Patients - A Randomized Double-blind Trial
- ClinicalTrials.gov ID
- NCT00798525
- Acronym / sponsor ID
- ALiCia / 2006-003122-28
- Conditions
- Heparin Induced Thrombocytopenia (HIT)
- Keywords
- thrombocytopenia, Heparin, Lepirudin, Argatroban, critically ill patients
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Supply of Lepirudin ended on 01. April 2012, thus trial terminated on 31. March 2012
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Heinrich-Heine University, DuesseldorfUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 26 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PR1 | Active comparator | Drug: ArgatrobanPatients treated with Argatroban (Argatra®), a direct thrombin inhibitor |
| PR2 | Active comparator | Drug: LepirudinPatients treated with Lepirudin (Refludan®), a direct thrombin inhibitor |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ArgatrobanAlso: Argatra®, MA number: 62085.00.0Argatra (Argatroban) will be diluted to 0.6 mg/ml and 0.5 µg/kg/min will be administered continuously in patients without liver disfunction. In patients with liver disfunction, defined by a bilirubin of > 4mg/dl, argatroban will be administered as a continuous infusion of 0,25 µg/kg/min with a final concentration of 0,3 mg/ml. | Drug | PR1 |
| LepirudinAlso: Refludan®, MA number: EU/1/97/035/003Refludan (Lepirudin) will be diluted to a final concentration of 0.1mg/ml and initiated as a continuous infusion of 5µg/kg/h in patients with continuous renal replacement therapy. In patients with moderate renal impairment (Creatinine ≥1,3 mg/dl) a final concentration 0,2 mg/ml of will be used to provide continuous infusion of 10 µg/kg/h. Patients without renal impairment (Creatinine < 1,3 mg/dl) will receive a continuous infusion of 50 µg/kg/h by a final concentration of 1 mg/ml of Lepirudin. | Drug | PR2 |
Primary outcome
Mean running time of a maximum of two consecutive haemodialysis circuits
Time frame: seven days starting at time of HIT suspicion
1 secondary outcome
Incidence of bleeding, transfusion requirements, thromboembolic events, anaphylactic reactions, and SUSARs, length of hospital stay, mortality, time till target aPTT
Time frame: seven days starting at time of HIT suspicion
Results and safety
The study was stopped early (reason given: Supply of Lepirudin ended on 01. April 2012, thus trial terminated on 31. March 2012). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2012.
- Derived from this study: PubMed 33314078Tsujimoto H, Tsujimoto Y, Nakata Y, Fujii T, Takahashi S, Akazawa M, Kataoka Y. Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2020 Dec 14;12(12):CD012467. doi: 10.1002/14651858.CD012467.pub3.
- Derived from this study: PubMed 29426286Beiderlinden M, Werner P, Bahlmann A, Kemper J, Brezina T, Schafer M, Gorlinger K, Seidel H, Kienbaum P, Treschan TA. Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry - a prospectively controlled randomized double-blind clinical trial. BMC Anesthesiol. 2018 Feb 9;18(1):18. doi: 10.1186/s12871-018-0475-y.
- Derived from this study: PubMed 25344113Treschan TA, Schaefer MS, Geib J, Bahlmann A, Brezina T, Werner P, Golla E, Greinacher A, Pannen B, Kindgen-Milles D, Kienbaum P, Beiderlinden M. Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial. Crit Care. 2014 Oct 25;18(5):588. doi: 10.1186/s13054-014-0588-8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Kienbaum, MD principal investigator
Uniklinik Düsseldorf, Klinik für Anästhesiologie
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Argatroban and Lepirudin in people with Heparin Induced Thrombocytopenia (HIT), run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Supply of Lepirudin ended on 01. April 2012, thus trial terminated on 31. March 2012). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean running time of a maximum of two consecutive haemodialysis circuits (time frame: seven days starting at time of HIT suspicion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00798525, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2012.