Reversal of the Antithrombotic Action of New Oral Anticoagulants (REVANT)
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|ClinicalTrials.gov Identifier: NCT01478282|
Recruitment Status : Unknown
Verified March 2012 by Gines Escolar, Fundació Clínic per la Recerca Biomèdica.
Recruitment status was: Recruiting
First Posted : November 23, 2011
Last Update Posted : March 12, 2012
The main goal of this study is to improve safety and efficiency of clinical practice with the new generation of oral anticoagulants.
- To determine the effect of new oral anticoagulants (dabigatran and rivaroxaban) on platelets and coagulation mechanisms under flow conditions.
- To evaluate the ability of the concentrates containing coagulation factors (PCCs and FVIIa) to reverse the effects induced by the new anticoagulants.
These studies will be carried out ex vivo in blood samples obtained from healthy volunteers undergoing oral anticoagulant therapy at doses of proven efficacy and safety used in previous clinical trials.
|Condition or disease||Intervention/treatment||Phase|
|Thrombosis Anticoagulant-induced Bleeding Anticoagulant Overdosage Hemorrhage||Drug: Rivaroxaban Drug: Dabigatran||Phase 4|
There is a lack of information on antidotes that could reverse the effects of new oral anticoagulants in patients that require a rapid restoration of their impaired hemostatic mechanisms. The present study seeks to improve the security and efficacy of the clinical practice with the new generation of oral anticoagulants.
- To assess the action of new oral anticoagulants (dabigatran y rivaroxaban) on hemostasis with specific interest on possible interference with platelet interactions and coagulation mechanisms under flow conditions;
- To evaluate comparatively the effects of coagulation factor concentrates of established efficacy (prothrombin complexes and rFVIIa) to reverse the alterations of hemostasis parameters induced by the new anticoagulants.
Studies will be performed ex vivo using blood samples from healthy individuals subjected to treatments with the new anticoagulants at doses of proven efficacy and safety (150mg/12 h for dabigatran and 20 mg/day for rivaroxaban). Blood samples from the participants will be spiked "in vitro" with know concentrations of the coagulation factors. Modifications in:
- morphometric parameters (platelet deposition and fibrin formation) in perfusion studies under flow conditions; and
- analytical tests evaluating changes in coagulation mechanisms (thrombin generation, ecarine and prothrombin times) will be determined.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Crossover Assignment|
|Official Title:||Evaluation of the Potential Action of Coagulation Factors Concentrates in the Reversal of the Antithrombotic Action of New Oral Anticoagulants: Studies ex Vivo in Blood Samples From Healthy Volunteers|
|Study Start Date :||January 2012|
|Estimated Primary Completion Date :||December 2012|
|Estimated Study Completion Date :||December 2012|
Active Comparator: Rivaroxaban
Healthy donors subjected to 20mg/day for 5 days
20 mg/day, oral administration maintained for 5 days
Other Name: Xarelto is the brand name for rivaroxaban
Active Comparator: Dabigatran
Healthy volunteers subjected to 150 mg/12hours for 5 days
150 mg/12 hours, administered orally, treatment maintained for 5 days
Other Name: Pradaxa is the brand name for dabigatran
- Modifications in hemostasis parameters. [ Time Frame: 5 days ]We will evaluate: a) the surface covered by platelets and fibrin on the subendothelium of vascular segments. Platelet interaction will be expressed as percentage of covered surface by platelets (%CS) and classified as contact, adhesion and aggregates depending of the size of interactions. Fibrin formation will be also evaluated as percentage of surface covered by fibrin (%F) and as the mean area of fibrin formed; and b) thrombin generation as lag time and maximum thrombin peak generation using a commercially available test (Technothrombin TGA, Technoclone GMBH).
- Changes observed after in vitro addition of coagulation factor concentrates [ Time Frame: 5 days ]We will re-evaluate: a) the surface covered by platelets and fibrin on the subendothelium of vascular segments. Platelet interaction will be expressed as percentage of covered surface by platelets (%CS) and classified as contact, adhesion and aggregates depending of the size of interactions. Fibrin formation will be also evaluated as percentage of surface covered by fibrin (%F) and as the mean area of fibrin formed; and b) thrombin generation as lag time and maximum thrombin peak generation using a commercially available test (Technothrombin TGA, Technoclone GMBH).
- Measure other indirect biomarkers of the activation of the coagulation mechanisms. [ Time Frame: 5 days ]Prothrombin time, ecarin clotting time, and F1+2 fragments will be determined in frozen plasma samples.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01478282
|Hospital Clinic, Fundació Clinic (FCRB)||Recruiting|
|Barcelona, Spain, 08036|
|Contact: Gines Escolar 34932275448 firstname.lastname@example.org|
|Sub-Investigator: Eduardo Arellano, M.D., Ph.D.|
|Sub-Investigator: Xavier Carne, M.D., Ph.D.|
|Principal Investigator: Gines Escolar, M.D., Ph.D.|
|Sub-Investigator: Ana M Galan, Ph.D.|
|Sub-Investigator: Juan Carlos Reverter, M.D., Ph.D.|
|Sub-Investigator: Jaume Villalta, M.D.|
|Principal Investigator:||Gines Escolar, M.D., Ph.D.||Fundacio Clinic per a la Reçerca Biomedica (FCRB)|