Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Anti-thrombotics
Condition: Venous Thromboembolism
MeSH terms: Thromboembolism; Venous Thromboembolism
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to evaluate whether the effect of the two new anticoagulants,
      Dabigatran and Rivaroxaban, can be reversed by non-specific and specific inhibitors. For
      Dabigatran the investigators will test the non-specific inhibitors: prothrombin complex
      concentrate (PCC), recombinant activated coagulation factor VII, and activated
      prothrombin-complex (FEIBA). For Rivaroxaban the investigators will test a specific
      Rivaroxaban decoy (FXa-GLAless). This will be done in a laboratory using blood plasma from
      healthy male volunteers.
    

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.
    

Intervention name(s): Rivaroxaban, Dabigatran; Dabigatran; Rivaroxaban
Intervention type(s): Drug; Drug
Intervention description(s): Rivaroxaban: One dose of 20mg (2 tablets of 10mg) then Dabigatran: One dose of 150mg(2 capsules of 75mg) two weeks later; Dabigatran: One dose of 150mg(2 capsules of 75mg) then Rivaroxaban: One dose of 20mg (2 tablets of 10mg)two weeks later
Other intervention name(s): Xarelto; Pradaxa; Pradaxa; Xarelto
Intervention MeSH terms: Rivaroxaban; Dabigatran
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Antithrombotics; Haemostatics; Antidote