Reversal of the Antithrombotic Action of New Oral Anticoagulants

Thrombosis Clinical Trial

— REVANT  

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

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT01478282
• Other study ID #: FCRB
• Secondary ID: 2010-022985-29
• Status: Unknown status
• Phase: Phase 4
• First received: November 8, 2011
• Last updated: March 9, 2012
• Start date: January 2012
• Est. completion date: December 2012

Study information

• Verified date: March 2012
• Source: Fundacion Clinic per a la Recerca Biomédica
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 10
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Anticoagulant Overdosage
• Anticoagulant-induced Bleeding
• Hemorrhage
• Thrombosis

Intervention

Drug:
• Rivaroxaban
20 mg/day, oral administration maintained for 5 days
• Dabigatran
150 mg/12 hours, administered orally, treatment maintained for 5 days

Locations

Country	Name	City	State
Spain	Hospital Clinic, Fundació Clinic (FCRB)	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Gines Escolar	Ministry of Health, Spain

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modifications in hemostasis parameters.	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).	5 days
Primary	Changes observed after in vitro addition of coagulation factor concentrates	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).	5 days
Secondary	Measure other indirect biomarkers of the activation of the coagulation mechanisms.	Prothrombin time, ecarin clotting time, and F1+2 fragments will be determined in frozen plasma samples.	5 days