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Reversal of the Antithrombotic Action of New Oral Anticoagulants (REVANT)

This study is currently recruiting participants.
Verified March 2012 by Fundacion Clinic per a la Recerca Biomédica
Sponsor:
Collaborator:
Ministry of Health, Spain
Information provided by (Responsible Party):
Gines Escolar, Fundació Clínic per la Recerca Biomèdica
ClinicalTrials.gov Identifier:
NCT01478282
First received: November 8, 2011
Last updated: March 9, 2012
Last verified: March 2012
History of Changes
  Purpose

The main goal of this study is to improve safety and efficiency of clinical practice with the new generation of oral anticoagulants.

  1. To determine the effect of new oral anticoagulants (dabigatran and rivaroxaban) on platelets and coagulation mechanisms under flow conditions.
  2. 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 Intervention Phase
Thrombosis
Anticoagulant-induced Bleeding
Anticoagulant Overdosage
Hemorrhage
 Drug: Rivaroxaban
Drug: Dabigatran
 Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
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

Resource links provided by NLM:

MedlinePlus related topics: Blood Thinners
U.S. FDA Resources

Further study details as provided by Fundacion Clinic per a la Recerca Biomédica:

Primary Outcome Measures:
  • Modifications in hemostasis parameters. [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Measure other indirect biomarkers of the activation of the coagulation mechanisms. [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    Prothrombin time, ecarin clotting time, and F1+2 fragments will be determined in frozen plasma samples.


Estimated Enrollment: 10
Study Start Date: January 2012
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rivaroxaban
Healthy donors subjected to 20mg/day for 5 days
 Drug: Rivaroxaban
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
 Drug: Dabigatran
150 mg/12 hours, administered orally, treatment maintained for 5 days
Other Name: Pradaxa is the brand name for dabigatran

Detailed Description:

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.

OBJECTIVES:

  1. 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;
  2. 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.

METHODOLOGY:

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.
  Eligibility

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteers ages from 21 to 60 years
  • Approval informed consent

Exclusion Criteria:

  • History of hepatic or kidney disease
  • Previous history of hemorrhagic or thrombotic disease
  • Pregnancy or breast feeding
  • Concomitant use of drugs affecting hemostasis
  • Use of medications of herbal treatments that could interfere with the pharmacokinetics or pharmacodynamics of the study drug (according to manufacturers label)
  • Practice of risky sports (during the study period)
  • Blood donation in the previous 3 months
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01478282

Locations
Spain
Hospital Clinic, Fundació Clinic (FCRB) Recruiting
Barcelona, Spain, 08036
Contact: Gines Escolar     34932275448     gescolar@clinic.ub.es    
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.            
Sponsors and Collaborators
Gines Escolar
Ministry of Health, Spain
Investigators
Principal Investigator: Gines Escolar, M.D., Ph.D. Fundacio Clinic per a la Reçerca Biomedica (FCRB)
  More Information

No publications provided

Responsible Party: Gines Escolar, head of department Hemotherapy-Hemostasis, Fundació Clínic per la Recerca Biomèdica
ClinicalTrials.gov Identifier: NCT01478282     History of Changes
Other Study ID Numbers: FCRB, 2010-022985-29
Study First Received: November 8, 2011
Last Updated: March 9, 2012
Health Authority: Spain: Spanish Agency of Medicines
Spain: Ministry of Health

Keywords provided by Fundacion Clinic per a la Recerca Biomédica:
dabigatran
rivaroxaban
oral anticoagulants
 coagulation
bleeding
plasma concentrates

Additional relevant MeSH terms:
Hemorrhage
Thrombosis
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
 Cardiovascular Diseases
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013