ThrombosisPhase 4REVANTNCT01478282
Reversal of the Antithrombotic Action of New Oral Anticoagulants
A Phase 4 study testing Rivaroxaban and Dabigatran in people with Thrombosis and Anticoagulant-induced Bleeding, run by Gines Escolar at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Thrombosis, Anticoagulant-induced Bleeding, Anticoagulant Overdosage
- What is being tested?
- Rivaroxaban and Dabigatran
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSpain
- Study dates
- Jan 2012to Dec 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteers ages from 21 to 60 years
- Approval informed consent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital Clinic, Fundació Clinic (FCRB)
Barcelona, Barcelona, 08036
Gines Escolar, 34932275448, gescolar@clinic.ub.es
Eduardo Arellano, M.D., Ph.D.
About this study
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
The main goal of this study is to improve safety and efficiency of clinical practice with the new generation of oral anticoagulants.
- To determine the effect of new oral anticoagulants (dabigatran and rivaroxaban) on platelets and coagulation mechanisms under flow conditions.
- 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.
Read the 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:
- 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;
- 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.
- Being tested
- Rivaroxaban, Dabigatran
- Keywords
- dabigatran, rivaroxaban, oral anticoagulants, coagulation, bleeding, plasma concentrates
- Medical subject headings
- Thrombosis, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivaroxabanDrug
Also called Xarelto is the brand name for rivaroxaban
20 mg/day, oral administration maintained for 5 days
DabigatranDrug
Also called Pradaxa is the brand name for dabigatran
150 mg/12 hours, administered orally, treatment maintained for 5 days
| Study group | Role | What they receive |
|---|---|---|
| Rivaroxaban | Active comparator | Healthy donors subjected to 20mg/day for 5 days Receives: Drug: Rivaroxaban |
| Dabigatran | Active comparator | Healthy volunteers subjected to 150 mg/12hours for 5 days Receives: Drug: Dabigatran |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 5 days
Secondary outcomes (1)
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.
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2012 (estimated)
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ThrombosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gines Escolar
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Spain
- Responsible party
- Sponsor-investigator, Gines Escolar, Fundacion Clinic per a la Recerca Biomédica
- Investigators
- Gines Escolar, M.D., Ph.D., Principal investigator, Fundacio Clinic per a la Reçerca Biomedica (FCRB)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01478282
- Sponsor's protocol ID
- FCRB
- Other IDs
- 2010-022985-29
- Acronym
- REVANT
- Status last verified
- Mar 2012
- First submitted
- 8 Nov 2011
- Last updated
- 12 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26364029
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01478282
- Acronym / sponsor ID
- REVANT / FCRB
- Keywords
- dabigatran, rivaroxaban, oral anticoagulants, coagulation, bleeding, plasma concentrates
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Gines EscolarUniversity, hospital or other
- Collaborators
- Ministry of Health, Spain
- Study start
- Jan 2012
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 23 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main goal of this study is to improve safety and efficiency of clinical practice with the new generation of oral anticoagulants.
- To determine the effect of new oral anticoagulants (dabigatran and rivaroxaban) on platelets and coagulation mechanisms under flow conditions.
- 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:
- 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;
- 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.
Study design
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rivaroxaban | Active comparator | Drug: RivaroxabanHealthy donors subjected to 20mg/day for 5 days |
| Dabigatran | Active comparator | Drug: DabigatranHealthy volunteers subjected to 150 mg/12hours for 5 days |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy volunteers ages from 21 to 60 years
- Approval informed consent
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RivaroxabanAlso: Xarelto is the brand name for rivaroxaban20 mg/day, oral administration maintained for 5 days | Drug | Rivaroxaban |
| DabigatranAlso: Pradaxa is the brand name for dabigatran150 mg/12 hours, administered orally, treatment maintained for 5 days | Drug | Dabigatran |
Primary outcome
Modifications in hemostasis parameters.
Time frame: 5 days
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
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).
1 secondary outcome
Measure other indirect biomarkers of the activation of the coagulation mechanisms.
Time frame: 5 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2012.
- Derived from this study: PubMed 26364029Arellano-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gines Escolar, M.D., Ph.D. principal investigator
Fundacio Clinic per a la Reçerca Biomedica (FCRB)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rivaroxaban and Dabigatran in people with Thrombosis and Anticoagulant-induced Bleeding, run by Gines Escolar at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modifications in hemostasis parameters. (time frame: 5 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01478282, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2012.