REVANT: Reversal of the Antithrombotic Action of New Oral Anticoagulants

Sponsor

Gines Escolar (Other)

Overall Status

Unknown status

CT.gov ID

NCT01478282

Collaborator

Ministry of Health, Spain (Other)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

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:

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.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Participant)

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 :

Jan 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2012

Anticipated Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Rivaroxaban Healthy donors subjected to 20mg/day for 5 days	Drug: Rivaroxaban 20 mg/day, oral administration maintained for 5 days Other Names: 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 Names: Pradaxa is the brand name for dabigatran

Arm

Intervention/Treatment

Active Comparator: Rivaroxaban

Healthy donors subjected to 20mg/day for 5 days

Drug: Rivaroxaban

20 mg/day, oral administration maintained for 5 days

Other Names:

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 Names:

Pradaxa is the brand name for dabigatran

Outcome Measures

Primary Outcome Measures

Modifications in hemostasis parameters. [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 [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).

Secondary Outcome Measures

Measure other indirect biomarkers of the activation of the coagulation mechanisms. [5 days]
Prothrombin time, ecarin clotting time, and F1+2 fragments will be determined in frozen plasma samples.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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