- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01210755
Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Anti-thrombotics (REVNEWANTICO)
Reversion of the Anticoagulant Effect of the New Antithrombotic Agents Anti-Xa and Anti IIa by Specific and Non-specific Haemostatic Drugs,: an Ex-Vivo Study in Healthy Volunteers
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background and objective:
Currently the most widely prescribed long term anticoagulant drugs are anti vitamin K agents (AVK). They should be used with caution because they are drugs that have a narrow therapeutic range: the difference between the effective dose and toxic dose is small. Their use thus requires careful laboratory monitoring. They can cause bleeding complications in the case of overdose. The AVKs have two antidotes: Vitamin K and prothrombin complex concentrates (PCC). These reverse the anticoagulant effect.
In recent years, new types of anticoagulants have been marketed in particular Rivaroxaban (Xarelto ®) and Dabigatran (Pradaxa ®). The way they act is different from that of AVK. They have the advantage of having a wider therapeutic range. Their use is therefore easier. They do not require such regular monitoring. However, currently, no antidote has been evaluated to reverse the effect of these anticoagulants in case of emergency.
The purpose of this study is to evaluate whether the effect of the two new anticoagulants can be reversed by non-specific and specific inhibitors. For Dabigatran we will test the non-specific inhibitors prothrombin complex concentrate (PCC), recombinant activated coagulation factor VII, and activated prothrombin complex (FEIBA). For Rivaroxaban we will test a specific Rivaroxaban decoy (FXa-GLAless). This will be done in a laboratory using blood plasma from healthy volunteers.
Methods:
This is a proof of concept, single centre, randomized, open, controlled, cross-over,phase IV study involving 10 healthy volunteers Each volunteer will be asked to attend an enrolment visit in which they will be given information about the study and asked to sign a written consent form. They will have an electrocardiogram test, their blood pressure and pulse will be measured, their medical history noted, and samples of blood and of urine will be taken.
At the second visit they will be given one dose of either Rivaroxaban (20mg) or of Dabigatran (150mg), allocated randomly, and 5 samples of blood (in total 67.5mL)will be taken over a period of 4 hours via a catheter. The blood samples will be immediately centrifuged and frozen.
At the 3rd visit, 15 days later, the volunteer will have a medical examination prior to taking the other drug. This visit will then follow the same procedure as the 2nd visit.
At the 4th visit a medical examination will be made and blood and urine samples taken.
Plasma samples will be analysed and challenged with the inhibitors in the biochemistry and haematology departments of Grenoble University Hospital.
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Locations
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-
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Grenoble, France, 38043
- Clinical Research Centre, University Hospital Grenoble
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male
- Age between 18 and 35 years
- Subject-free any acute or chronic disease
- Subjects who signed the written informed consent
- Subject affiliated to French social security or beneficiary of a similar health insurance scheme
Exclusion Criteria:
Any subjects with at least one of the following:
- Female
- Body mass index <19 and > 29
- Active or being treated for angina, coronary syndrome, stroke or arterial disease
- Constitutional hemorrhagic disease
- Acquired bleeding disorder
- Presenting or treated for any liver disease
- Abnormal laboratory results for liver function
- History of venous thrombotic disease
- History of heparin induced Thrombocytopenia
- Surgery in the previous month
- Surgery planned within a month
- Creatinine clearance below 60 ml / min
- Clinically significant bleeding or progressive disease at risk of increased bleeding (congenital or acquired hemorrhagic syndromes, uncontrolled severe hypertension, evolving gastrointestinal ulcerative disease, recent history of gastrointestinal ulcer, vascular retinopathy, recent intracranial or intracerebral hemorrhage, intrathecal or intracerebral vascular anomalies, brain, spinal or ophthalmological surgery recently)
- Hypersensitivity to the active substance or any excipients
- Person deprived of liberty by judicial or administrative order or person subject to an order of legal protection
- Refusal of consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Rivaroxaban then Dabigatran
Cross-over study with 15 days between administration of Rivaroxaban and Dabigatran
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Rivaroxaban: One dose of 20mg (2 tablets of 10mg) then Dabigatran: One dose of 150mg(2 capsules of 75mg) two weeks later
Other Names:
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Experimental: Dabigatran then Rivaroxaban
Cross-over study with 15 days between administration of Dabigatran and Rivaroxaban
|
Dabigatran: One dose of 150mg(2 capsules of 75mg) then Rivaroxaban: One dose of 20mg (2 tablets of 10mg)two weeks later
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
In vitro Reversal of anticoagulation
Time Frame: just before and 1, 2, 3 and 4 hours after taking medicine
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Reversal of anticoagulation by return of thrombin generation time to normal value
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just before and 1, 2, 3 and 4 hours after taking medicine
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
In vitro, activated partial thromboplastin time
Time Frame: just before and 1, 2, 3 and 4 hours after taking medicine
|
|
just before and 1, 2, 3 and 4 hours after taking medicine
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Gilles Pernod, MD, University Hospital, Grenoble
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- DCIC 10 09
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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