Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Reversal of the Antithrombotic Action of New Oral Anticoagulants (REVANT)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by Fundacion Clinic per a la Recerca Biomédica.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Ministry of Health, Spain
Information provided by (Responsible Party):
Gines Escolar, Fundació Clínic per la Recerca Biomèdica
ClinicalTrials.gov Identifier:
NCT01478282
First received: November 8, 2011
Last updated: March 9, 2012
Last verified: March 2012

November 8, 2011
March 9, 2012
January 2012
December 2012   (final data collection date for primary outcome measure)
  • Modifications in hemostasis parameters. [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    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).
Same as current
Complete list of historical versions of study NCT01478282 on ClinicalTrials.gov Archive Site
Measure other indirect biomarkers of the activation of the coagulation mechanisms. [ Time Frame: 5 days ] [ Designated as safety issue: No ]
Prothrombin time, ecarin clotting time, and F1+2 fragments will be determined in frozen plasma samples.
Same as current
Not Provided
Not Provided
 
Reversal of the Antithrombotic Action of New Oral Anticoagulants
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

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.

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.
Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
  • Thrombosis
  • Anticoagulant-induced Bleeding
  • Anticoagulant Overdosage
  • Hemorrhage
  • Drug: Rivaroxaban
    20 mg/day, oral administration maintained for 5 days
    Other Name: Xarelto is the brand name for rivaroxaban
  • Drug: Dabigatran
    150 mg/12 hours, administered orally, treatment maintained for 5 days
    Other Name: Pradaxa is the brand name for dabigatran
  • Active Comparator: Rivaroxaban
    Healthy donors subjected to 20mg/day for 5 days
    Intervention: Drug: Rivaroxaban
  • Active Comparator: Dabigatran
    Healthy volunteers subjected to 150 mg/12hours for 5 days
    Intervention: Drug: Dabigatran
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
10
December 2012
December 2012   (final data collection date for primary outcome measure)

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
Both
21 Years to 60 Years
Yes
Spain
 
NCT01478282
FCRB, 2010-022985-29
No
Gines Escolar, Fundació Clínic per la Recerca Biomèdica
Gines Escolar
Ministry of Health, Spain
Principal Investigator: Gines Escolar, M.D., Ph.D. Fundacio Clinic per a la Reçerca Biomedica (FCRB)
Fundacion Clinic per a la Recerca Biomédica
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP