Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Anti-thrombotics

NCT ID: NCT01210755

Last Updated: 2011-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2011-06-30

Brief Summary

The purpose of this study is to evaluate whether the effect of the two new anticoagulants, Dabigatran and Rivaroxaban, can be reversed by non-specific and specific inhibitors. For Dabigatran the investigators will test the non-specific inhibitors: prothrombin complex concentrate (PCC), recombinant activated coagulation factor VII, and activated prothrombin-complex (FEIBA). For Rivaroxaban the investigators will test a specific Rivaroxaban decoy (FXa-GLAless). This will be done in a laboratory using blood plasma from healthy male volunteers.

Detailed Description

Background and objective:

Currently the most widely prescribed long term anticoagulant drugs are anti vitamin K agents (AVK). They should be used with caution because they are drugs that have a narrow therapeutic range: the difference between the effective dose and toxic dose is small. Their use thus requires careful laboratory monitoring. They can cause bleeding complications in the case of overdose. The AVKs have two antidotes: Vitamin K and prothrombin complex concentrates (PCC). These reverse the anticoagulant effect.

In recent years, new types of anticoagulants have been marketed in particular Rivaroxaban (Xarelto ®) and Dabigatran (Pradaxa ®). The way they act is different from that of AVK. They have the advantage of having a wider therapeutic range. Their use is therefore easier. They do not require such regular monitoring. However, currently, no antidote has been evaluated to reverse the effect of these anticoagulants in case of emergency.

The purpose of this study is to evaluate whether the effect of the two new anticoagulants can be reversed by non-specific and specific inhibitors. For Dabigatran we will test the non-specific inhibitors prothrombin complex concentrate (PCC), recombinant activated coagulation factor VII, and activated prothrombin complex (FEIBA). For Rivaroxaban we will test a specific Rivaroxaban decoy (FXa-GLAless). This will be done in a laboratory using blood plasma from healthy volunteers.

Methods:

This is a proof of concept, single centre, randomized, open, controlled, cross-over,phase IV study involving 10 healthy volunteers Each volunteer will be asked to attend an enrolment visit in which they will be given information about the study and asked to sign a written consent form. They will have an electrocardiogram test, their blood pressure and pulse will be measured, their medical history noted, and samples of blood and of urine will be taken.

At the second visit they will be given one dose of either Rivaroxaban (20mg) or of Dabigatran (150mg), allocated randomly, and 5 samples of blood (in total 67.5mL)will be taken over a period of 4 hours via a catheter. The blood samples will be immediately centrifuged and frozen.

At the 3rd visit, 15 days later, the volunteer will have a medical examination prior to taking the other drug. This visit will then follow the same procedure as the 2nd visit.

At the 4th visit a medical examination will be made and blood and urine samples taken.

Plasma samples will be analysed and challenged with the inhibitors in the biochemistry and haematology departments of Grenoble University Hospital.

Conditions

Venous Thromboembolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Rivaroxaban then Dabigatran

Cross-over study with 15 days between administration of Rivaroxaban and Dabigatran

Group Type: EXPERIMENTAL

Rivaroxaban, Dabigatran

Intervention Type: DRUG

Rivaroxaban: One dose of 20mg (2 tablets of 10mg) then Dabigatran: One dose of 150mg(2 capsules of 75mg) two weeks later

Dabigatran then Rivaroxaban

Cross-over study with 15 days between administration of Dabigatran and Rivaroxaban

Group Type: EXPERIMENTAL

Dabigatran; Rivaroxaban

Intervention Type: DRUG

Dabigatran: One dose of 150mg(2 capsules of 75mg) then Rivaroxaban: One dose of 20mg (2 tablets of 10mg)two weeks later

Interventions

Rivaroxaban, Dabigatran

Rivaroxaban: One dose of 20mg (2 tablets of 10mg) then Dabigatran: One dose of 150mg(2 capsules of 75mg) two weeks later

Intervention Type: DRUG

Dabigatran; Rivaroxaban

Dabigatran: One dose of 150mg(2 capsules of 75mg) then Rivaroxaban: One dose of 20mg (2 tablets of 10mg)two weeks later

Intervention Type: DRUG

Other Intervention Names

Xarelto; Pradaxa; Pradaxa; Xarelto

Eligibility Criteria

Inclusion Criteria

• Male
• Age between 18 and 35 years
• Subject-free any acute or chronic disease
• Subjects who signed the written informed consent
• Subject affiliated to French social security or beneficiary of a similar health insurance scheme

Exclusion Criteria

Any subjects with at least one of the following:

• Female
• Body mass index <19 and > 29
• Active or being treated for angina, coronary syndrome, stroke or arterial disease
• Constitutional hemorrhagic disease
• Acquired bleeding disorder
• Presenting or treated for any liver disease
• Abnormal laboratory results for liver function
• History of venous thrombotic disease
• History of heparin induced Thrombocytopenia
• Surgery in the previous month
• Surgery planned within a month
• Creatinine clearance below 60 ml / min
• Clinically significant bleeding or progressive disease at risk of increased bleeding (congenital or acquired hemorrhagic syndromes, uncontrolled severe hypertension, evolving gastrointestinal ulcerative disease, recent history of gastrointestinal ulcer, vascular retinopathy, recent intracranial or intracerebral hemorrhage, intrathecal or intracerebral vascular anomalies, brain, spinal or ophthalmological surgery recently)
• Hypersensitivity to the active substance or any excipients
• Person deprived of liberty by judicial or administrative order or person subject to an order of legal protection
• Refusal of consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Grenoble

OTHER

Sponsor Role: lead

Responsible Party

University Hospital, Grenoble

Principal Investigators

Gilles Pernod, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Grenoble

Locations

Clinical Research Centre, University Hospital Grenoble

Grenoble, , France

Countries

France

Other Identifiers

DCIC 10 09

Identifier Type: -

Identifier Source: org_study_id