Clinical trial NCT01478282: Reversal of the Antithrombotic Action of New Oral Anticoagulants
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Thrombosis
Anticoagulant-induced Bleeding
Anticoagulant Overdosage
Hemorrhage
Keywords: dabigatran
rivaroxaban
oral anticoagulants
coagulation
bleeding
plasma concentrates
Lead sponsor: Fundacion Clinic per a la Recerca Biomédica
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Spain
First posted: 2011-11-23
Enrollment: 10
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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.

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 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

Primary outcomes:
measure: Modifications in hemostasis parameters.
timeFrame: 5 days
measure: Changes observed after in vitro addition of coagulation factor concentrates
timeFrame: 5 days
Secondary outcomes:
measure: Measure other indirect biomarkers of the activation of the coagulation mechanisms.
timeFrame: 5 days
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clinic, Fundació Clinic (FCRB)
Study officials:
affiliation: Fundacio Clinic per a la Reçerca Biomedica (FCRB)
name: Gines Escolar, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arellano-Rodrigo E, Lopez-Vilchez I, Galan AM, Molina P, Reverter JC, Carne X, Villalta J, Tassies D, Lozano M, Diaz-Ricart M, Escolar G. Coagulation Factor Concentrates Fail to Restore Alterations in Fibrin Formation Caused by Rivaroxaban or Dabigatran in Studies With Flowing Blood From Treated Healthy Volunteers. Transfus Med Rev. 2015 Oct;29(4):242-9. doi: 10.1016/j.tmrv.2015.08.001. Epub 2015 Aug 8.