Reversal of the Antithrombotic Action of New Oral Anticoagulants

NCT01478282 | Unknown Phase 4

• 2 other identifiers: FCRB2010-022985-29
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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. 1.To determine the effect of new oral anticoagulants (dabigatran and rivaroxaban) on platelets and coagulation mechanisms under flow conditions.
2. 2.To evaluate the ability of the concentrates containing coagulation factors (PCCs and FVIIa) to reverse the effects induced by the new anticoagulants.

Conditions

Thrombosis; Anticoagulant-induced Bleeding; Anticoagulant Overdosage; Hemorrhage

Keywords

dabigatran; rivaroxaban; oral anticoagulants; coagulation; bleeding; plasma concentrates

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (1)

• Measure other indirect biomarkers of the activation of the coagulation mechanisms.

  5 days

Study Arms (2)

Rivaroxaban

ACTIVE COMPARATOR

Healthy donors subjected to 20mg/day for 5 days

Drug: Rivaroxaban

Dabigatran

ACTIVE COMPARATOR

Healthy volunteers subjected to 150 mg/12hours for 5 days

Drug: Dabigatran

Interventions

Rivaroxaban DRUG

20 mg/day, oral administration maintained for 5 days

Also known as: Xarelto is the brand name for rivaroxaban

Rivaroxaban

Dabigatran DRUG

150 mg/12 hours, administered orally, treatment maintained for 5 days

Also known as: Pradaxa is the brand name for dabigatran

Dabigatran

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gines Escolar: lead
• Ministry of Health, Spain: collaborator

Study Sites (1)

Hospital Clinic, Fundació Clinic (FCRB)

Barcelona, Barcelona, 08036, Spain

RECRUITING

Related Publications (1)

• 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.

  PMID: 26364029 DERIVED

MeSH Terms

Conditions

Thrombosis; Hemorrhage

Interventions

Rivaroxaban; Dabigatran

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gines Escolar, M.D., Ph.D.

  Fundacio Clinic per a la Reçerca Biomedica (FCRB)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: head of department Hemotherapy-Hemostasis

Study Record Dates

• First Submitted: November 8, 2011
• First Posted: November 23, 2011
• Study Start: January 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 12, 2012

Record last verified: 2012-03

Locations

ES (1)