Venous ThromboembolismPhase 4REVNEWANTICONCT01210755
Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Anti-thrombotics
A Phase 4 study testing Rivaroxaban, Dabigatran and Dabigatran; Rivaroxaban in people with Venous Thromboembolism, run by University Hospital, Grenoble at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- Rivaroxaban, Dabigatran and Dabigatran; Rivaroxaban
- 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 siteFrance
- Study dates
- Nov 2010to Jun 2011
- 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 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Clinical Research Centre, University Hospital Grenoble
Grenoble, 38043
About this study
Official title: Reversion of the Anticoagulant Effect of the New Antithrombotic Agents Anti-Xa and Anti IIa by Specific and Non-specific Haemostatic Drugs,: an Ex-Vivo Study in Healthy Volunteers
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.
Read the 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
- Being tested
- Rivaroxaban, Dabigatran, Dabigatran; Rivaroxaban
- Keywords
- Antithrombotics, Haemostatics, Antidote
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rivaroxaban, DabigatranDrug
Also called Xarelto, Pradaxa
Rivaroxaban: One dose of 20mg (2 tablets of 10mg) then Dabigatran: One dose of 150mg(2 capsules of 75mg) two weeks later
Dabigatran; RivaroxabanDrug
Also called Pradaxa, Xarelto
Dabigatran: One dose of 150mg(2 capsules of 75mg) then Rivaroxaban: One dose of 20mg (2 tablets of 10mg)two weeks later
| Study group | Role | What they receive |
|---|---|---|
| Rivaroxaban then Dabigatran | Experimental | Cross-over study with 15 days between administration of Rivaroxaban and Dabigatran Receives: Drug: Rivaroxaban, Dabigatran |
| Dabigatran then Rivaroxaban | Experimental | Cross-over study with 15 days between administration of Dabigatran and Rivaroxaban Receives: Drug: Dabigatran; Rivaroxaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
In vitro Reversal of anticoagulation
Reversal of anticoagulation by return of thrombin generation time to normal value
Measured: just before and 1, 2, 3 and 4 hours after taking medicine
Secondary outcomes (1)
In vitro, activated partial thromboplastin time
- Thrombin time, activated partial thromboplastin time.
- Prothrombin time, measurement of anti Xa activity.
Measured: just before and 1, 2, 3 and 4 hours after taking medicine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2010 (estimated)
- Study startNov 2010
- Primary completionMar 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- 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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Investigators
- Gilles Pernod, MD, Principal investigator, University Hospital, Grenoble
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01210755
- Sponsor's protocol ID
- DCIC 10 09
- Acronym
- REVNEWANTICO
- Status last verified
- Jun 2011
- First submitted
- 27 Sep 2010
- Last updated
- 1 Jul 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reversion of the Anticoagulant Effect of the New Antithrombotic Agents Anti-Xa and Anti IIa by Specific and Non-specific Haemostatic Drugs,: an Ex-Vivo Study in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01210755
- Acronym / sponsor ID
- REVNEWANTICO / DCIC 10 09
- Conditions
- Venous Thromboembolism
- Keywords
- Antithrombotics, Haemostatics, Antidote
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- Nov 2010
- Primary completion
- Mar 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 28 Sep 2010 (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 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rivaroxaban then Dabigatran | Experimental | Drug: Rivaroxaban, DabigatranCross-over study with 15 days between administration of Rivaroxaban and Dabigatran |
| Dabigatran then Rivaroxaban | Experimental | Drug: Dabigatran; RivaroxabanCross-over study with 15 days between administration of Dabigatran and Rivaroxaban |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- 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
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 |
|---|---|---|
| Rivaroxaban, DabigatranAlso: Xarelto, PradaxaRivaroxaban: One dose of 20mg (2 tablets of 10mg) then Dabigatran: One dose of 150mg(2 capsules of 75mg) two weeks later | Drug | Rivaroxaban then Dabigatran |
| Dabigatran; RivaroxabanAlso: Pradaxa, XareltoDabigatran: One dose of 150mg(2 capsules of 75mg) then Rivaroxaban: One dose of 20mg (2 tablets of 10mg)two weeks later | Drug | Dabigatran then Rivaroxaban |
Primary outcome
In vitro Reversal of anticoagulation
Time frame: just before and 1, 2, 3 and 4 hours after taking medicine
Reversal of anticoagulation by return of thrombin generation time to normal value
1 secondary outcome
In vitro, activated partial thromboplastin time
Time frame: just before and 1, 2, 3 and 4 hours after taking medicine
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2011.
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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.
Gilles Pernod, MD principal investigator
University Hospital, Grenoble
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, Dabigatran and Dabigatran; Rivaroxaban in people with Venous Thromboembolism, run by University Hospital, Grenoble at 1 site in France.
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 5 inclusion and 17 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: finished, as of the sponsor's last update on 1 Jul 2011. 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 France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
In vitro Reversal of anticoagulation (time frame: just before and 1, 2, 3 and 4 hours after taking medicine). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jul 2011.