Coagulation DisorderECANNCT03136510
Evolution of Coagulation Activity in Non Valvular Atrial Fibrillation Patients Under Apixaban
A study testing Apixaban 5 mg in people with Coagulation Disorder and Non Valvular Atrial Fibrillation, run by Hopital Lariboisière at 1 site in France.
Trial summary
Apixaban is a potent, oral, selective reversible direct inhibitor of factor Xa with a favorable efficacy and safety profile in the prevention of non valvular (NV) atrial fibrillation (AF). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coagulation Disorder, Non Valvular Atrial Fibrillation
- What is being tested?
- Apixaban 5 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2016to Mar 2019
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with NVAF (documented by 12 leads ECG or Holter recording) and having one or more factor (s) of risk such as: history of stroke or transient ischemic attack ; age≥75 years; hypertension; diabetes; symptomatic heart failure (NYHA class≥ II) for prevention of cerebral vascular accident and systemic embolism.
- Patients with CHA2DS2-VASc score ≥2
- Patients provided signed written informed consent
- Patients with age≥18 years
- Patients previously treated with VKA or patients newly diagnosed with AF.
Who cannot join
- AF or flutter due to reversible causes according to investigator
- Clinically significant mitral stenosis
- Any other condition than atrial fibrillation that require chronic anticoagulation (prosthetic heart valve or valve repair, venous thromboembolism)
- A need for aspirin at a dose of ≥160 mg a day or for both aspirin and adenosine diphosphate (ADP) inhibitor (clopidogrel, prasugrel or ticagrelor)
- Allergy or adverse reaction to apixaban or any of the excipients
- Patients previously treated by an oral direct anticoagulant in the last 30 days
Show all 16Show fewer
- Patient with clinically on going active bleeding or platelet count<100,000/mm3 or haemoglobin<9 g/dL
- Patients with serious bleeding in the last 6 months or with high risk of bleeding (active peptic ulcer disease or gastroduodenal ulceration, known or suspected esophageal varicoses, recent ischemic stroke, recent brain or spinal injury or intracranial hemorrhage, recent surgery, arterial or venous malformations, vascular aneurysms…)
- Patients with another cause of increase of D-dimers (active malignant neoplasm, recent trauma or surgery (less than 1 month), extensive venous malformation…)
- Uncontrolled and persistent hypertension (systolic >180 mmHg or diastolic >100 mmHg)
- Active infective endocarditis
- aspartate transaminase (ASAT) or alanine aminotransferase (ALAT) > 2 times upper limit or hepatic disease with coagulopathy
- Severe renal insufficiency (creatinine clearance <30ml/min)
- Women in age of pregnancy without menopause or efficient contraception and pregnant women or breast feeding women. Men without effective contraception.
- Any reason that makes the study participation impractical (alcohol abuse, psychosocial reason, inclusion in another study in the past month, life expectancy≤1 year…)
- Any contraindications to study treatment (apixaban): hypersensitivity to apixaban or any of the excipients (see composition), ongoing active bleeding, hepatic disease with coagulopathy, any condition with high risk of bleeding, concomitant anticoagulant treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective Study With Biological Assessment: Evolution of Coagulation Activity in Non Valvular Atrial Fibrillation Patients Under Apixaban
Apixaban is a potent, oral, selective reversible direct inhibitor of factor Xa with a favorable efficacy and safety profile in the prevention of non valvular (NV) atrial fibrillation (AF). It has been shown, including by our group, that D-dimers levels (molecular marker of coagulation activity) are predictive of the events (including mortality) in patient with AF independently of the antithrombotic treatment. The aim of the study is to evaluate the changes in plasma levels of biomarkers of coagulation activation: D-dimers, prothrombin fragments F1+2, von Willebrand factor (vWF) and thrombin-antithrombin complexes (TAT) in response to apixaban treatment in patients with NVAF.
Read the detailed description
This study is a prospective, monocentric study, with biological analyses. The investigational product will be administered according to French health agency. The duration of the study for each patient will be 3 months with 3 visits and from 3 to a maximum of 18 months for the clinical follow-up.
Hypothesis: Apixaban significantly decreases D-dimers and other markers of coagulation activation in patients with NVAF ( paroxysmic and chronic atrial fibrillation).
Primary endpoint:
Measurement of D-dimers at baseline (before apixaban treatment) and under chronic apixaban treatment at 3 months in the overall population.
Secondary endpoints:
Difference of the D-dimers levels between enrollment (V1) and the final visit (V3) at three months in both subgroups separately. In the subgroup B,comparison of D-dimers in patients previously treated by VKA (V1) and under apixaban (V3).
Similarly than for D-dimers levels, each following parameters will be analyzed for the overall population and for both subgroups separately :
- Difference of prothrombin fragments F1+F2 levels between V1 and V3.
- Difference of thrombin and antithrombin complexes levels between V1 and V3
- Difference of vWF levels between V1 and V3.
Correlation will be evaluated between:
- AntiXa apixaban activity (at trough) and D-dimers difference
- D-dimers difference and clinical follow-up (ischemic events and-bleeding events) V2 and V3 levels of each parameter will be compared to assess the delay of appearance of the apixaban effect if any. Inflammation parameters ( C reactive protein and fibrinogen) will be used as explicative for the other parameters.
Effect on APTT( activated partial thromboplastin time) and PT(prothrombin time) will be compared to specific apixaban anti Xa activity
Subgroup analysis:
- Subgroups A and B (newly diagnosed and VKA naïve NVAF and chronic NVAF)
- age >80 years,
- creatinine clearance < 50 ml/min,
- gender Multivariate analysis for the primary endpoint
Statistical analysis Continuous variables will be analyzed for a normal distribution with the D'Agostino-Pearson test. They will be presented as mean and standard deviation (SD) and compared with Student's unpaired t-test if normally distributed, or presented as median and interquartile range and compared with Mann-Whitney rank-sum test, if not. Categorical variables will be presented as counts and percentages and will be compared by means of the χ2-test or Fisher's exact test.
Correlations between quantitative variables will be assessed with Pearson correlation coefficients. Predictive factors will be determined using a stepwise multivariable logistic regression analysis. In this study, we will expect an initial D-dimers level around 1500ng/ml with a standard deviation of ±700ng/ml in patients with newly diagnosed NVAF. At 3 month, we expect a level of D-dimers of 1000±600ng/ml (reduction of 500ng/ml compared to the enrolment visit). A sample size of 60 patients has been estimated in this pilot study. The study will include 60 patients with NVAF with 50% of patients with newly diagnosed NVAF (Subgroup A, n=30) and the other 50% with NVAF previously treated by VKA (Subgroup B, n=30).
All information required by the protocol must be provided in the case report form. The data will be transferred in the case report forms as and when they are obtained, whether clinical or biological. The investigators will make the data available strictly necessary for qua lity control and audit relating to the biomedical research in accordance with the legislative and regulatory provisions in force (Articles L.1121-3 and R.5121-13 of the French Public Health Code).
Those responsible for biomedical research quality control (Article L.1121-3 of the French Public Health Code) will take all necessary precautions to ensure the confidentiality of information about the experimental medications, the research, the research subjects and in particular the identity of the subjects and the results obtained. These individuals, as well as the investigators themselves, are subject to professional secrecy (in accordance with the conditions set out in Articles 226-13 and 226-14 of the Penal Code).
All Serious Adverse Events (SAEs) that occur following the subject's written consent to participate in the study through 30 days of discontinuation of dosing must be reported to Bristol-Myers Squibb Worldwide Safety and to the sponsor.
- Being tested
- Apixaban 5 mg
- Medical subject headings
- Hemostatic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apixaban 5 mgDrug
Also called Eliquis
Bood collection for biological analyses at:
- inclusion visit
- follow-up visit at 1 month
- end of research at 3 month
| Study group | Role | What they receive |
|---|---|---|
| Newly diagnosed NVAF: apixaban 5 mg | Other | blood collection for biological analyses of 30 patients new diagnosis of NVAF (VKA treatment ≤1 week) initiated with apixaban 5 mg Receives: Drug: Apixaban 5 mg |
| Previously diagnosed NVAF: apixaban 5 mg | Other | blood collection for biological analyses of 30 patients previously treated by VKA for more than 3 months switched to apixaban 5 mg Receives: Drug: Apixaban 5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
change from baseline D-dimers level at 3 months.
D-dimers levels will be determined using an enzyme immunoassay (ELISA method) on citrated plasma.
Measured: 3 months
Secondary outcomes (6)
Prothrombin fragment F1-F2 measurement
Prothrombin fragment F1-F2 will be determined using an enzyme immunoassay (ELISA method) on citrated plasma.
Measured: at enrollment, at one month, and at three months
von Willebrand factor measurement
vWF will be determined using an enzyme immunoassay (ELISA method) on citrated plasma.
Measured: at enrollment, at one month, and at three months
Thrombin-antithrombin complex measurement
TAT complex will be determined using an enzyme immunoassay (ELISA method) on citrated plasma.
Measured: at enrollment, at one month, and at three months
High sensitivity CRP measurement
Hs CRP will be measured following usual method of the biochemistry laboratory on EDTA (ethylenediaminetetraacetic acid ) plasma.
Measured: at enrollment, at one month, and at three months
Prothrombin time measurement, Activated partial thromboplastin time, and fibrinogen
Prothrombin time, a PTT and fibrinogen will be measured following usual method of the hematology laboratory on citrated plasma.
Measured: at enrollment, at one month, and at three months
AntiXa apixaban activity measurement
Anti-Xa apixaban levels will be determined using the specific technic with adapted apixaban calibrators on citrated plasma.
Measured: at enrollment, at one month, and at three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2017
- Study startSep 2016
- Primary completionDec 2018
- Study completionMar 2019
Why it stopped: not enough patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coagulation DisorderStudies 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 N/A
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 60 patients with two subgroups * 30 patients with new diagnosis of atrial fibrillation (vitamin K antagonist treatment shorter than 1 week) : initiated with Apixaban 5 mg * 30 patients previously chronically treated by VKA for more than 3 months and switched to Apixaban 5 mg
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hopital Lariboisière
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Jean-Guillaume DILLINGER, Hopital Lariboisière
- Investigators
- Ludovic DROUET, MD, PhD, Study director, Lariboisiere Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03136510
- Sponsor's protocol ID
- CV185-439
- Acronym
- ECAN
- Status last verified
- Mar 2019
- First submitted
- 24 Apr 2017
- Last updated
- 26 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study With Biological Assessment: Evolution of Coagulation Activity in Non Valvular Atrial Fibrillation Patients Under Apixaban
- ClinicalTrials.gov ID
- NCT03136510
- Acronym / sponsor ID
- ECAN / CV185-439
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: not enough patients
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Hopital LariboisièreUniversity, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 2 May 2017 (actual)
- 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.
Apixaban is a potent, oral, selective reversible direct inhibitor of factor Xa with a favorable efficacy and safety profile in the prevention of non valvular (NV) atrial fibrillation (AF). It has been shown, including by our group, that D-dimers levels (molecular marker of coagulation activity) are predictive of the events (including mortality) in patient with AF independently of the antithrombotic treatment. The aim of the study is to evaluate the changes in plasma levels of biomarkers of coagulation activation: D-dimers, prothrombin fragments F1+2, von Willebrand factor (vWF) and thrombin-antithrombin complexes (TAT) in response to apixaban treatment in patients with NVAF.
Detailed description
This study is a prospective, monocentric study, with biological analyses. The investigational product will be administered according to French health agency. The duration of the study for each patient will be 3 months with 3 visits and from 3 to a maximum of 18 months for the clinical follow-up.
Hypothesis: Apixaban significantly decreases D-dimers and other markers of coagulation activation in patients with NVAF ( paroxysmic and chronic atrial fibrillation).
Primary endpoint:
Measurement of D-dimers at baseline (before apixaban treatment) and under chronic apixaban treatment at 3 months in the overall population.
Secondary endpoints:
Difference of the D-dimers levels between enrollment (V1) and the final visit (V3) at three months in both subgroups separately. In the subgroup B,comparison of D-dimers in patients previously treated by VKA (V1) and under apixaban (V3).
Similarly than for D-dimers levels, each following parameters will be analyzed for the overall population and for both subgroups separately :
- Difference of prothrombin fragments F1+F2 levels between V1 and V3.
- Difference of thrombin and antithrombin complexes levels between V1 and V3
- Difference of vWF levels between V1 and V3.
Correlation will be evaluated between:
- AntiXa apixaban activity (at trough) and D-dimers difference
- D-dimers difference and clinical follow-up (ischemic events and-bleeding events) V2 and V3 levels of each parameter will be compared to assess the delay of appearance of the apixaban effect if any. Inflammation parameters ( C reactive protein and fibrinogen) will be used as explicative for the other parameters.
Effect on APTT( activated partial thromboplastin time) and PT(prothrombin time) will be compared to specific apixaban anti Xa activity
Subgroup analysis:
- Subgroups A and B (newly diagnosed and VKA naïve NVAF and chronic NVAF)
- age >80 years,
- creatinine clearance < 50 ml/min,
- gender Multivariate analysis for the primary endpoint
Statistical analysis Continuous variables will be analyzed for a normal distribution with the D'Agostino-Pearson test. They will be presented as mean and standard deviation (SD) and compared with Student's unpaired t-test if normally distributed, or presented as median and interquartile range and compared with Mann-Whitney rank-sum test, if not. Categorical variables will be presented as counts and percentages and will be compared by means of the χ2-test or Fisher's exact test.
Correlations between quantitative variables will be assessed with Pearson correlation coefficients. Predictive factors will be determined using a stepwise multivariable logistic regression analysis. In this study, we will expect an initial D-dimers level around 1500ng/ml with a standard deviation of ±700ng/ml in patients with newly diagnosed NVAF. At 3 month, we expect a level of D-dimers of 1000±600ng/ml (reduction of 500ng/ml compared to the enrolment visit). A sample size of 60 patients has been estimated in this pilot study. The study will include 60 patients with NVAF with 50% of patients with newly diagnosed NVAF (Subgroup A, n=30) and the other 50% with NVAF previously treated by VKA (Subgroup B, n=30).
All information required by the protocol must be provided in the case report form. The data will be transferred in the case report forms as and when they are obtained, whether clinical or biological. The investigators will make the data available strictly necessary for qua lity control and audit relating to the biomedical research in accordance with the legislative and regulatory provisions in force (Articles L.1121-3 and R.5121-13 of the French Public Health Code).
Those responsible for biomedical research quality control (Article L.1121-3 of the French Public Health Code) will take all necessary precautions to ensure the confidentiality of information about the experimental medications, the research, the research subjects and in particular the identity of the subjects and the results obtained. These individuals, as well as the investigators themselves, are subject to professional secrecy (in accordance with the conditions set out in Articles 226-13 and 226-14 of the Penal Code).
All Serious Adverse Events (SAEs) that occur following the subject's written consent to participate in the study through 30 days of discontinuation of dosing must be reported to Bristol-Myers Squibb Worldwide Safety and to the sponsor.
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- 60 patients with two subgroups * 30 patients with new diagnosis of atrial fibrillation (vitamin K antagonist treatment shorter than 1 week) : initiated with Apixaban 5 mg * 30 patients previously chronically treated by VKA for more than 3 months and switched to Apixaban 5 mg
| Arm | Type | Receives |
|---|---|---|
| Newly diagnosed NVAF: apixaban 5 mg | Other | Drug: Apixaban 5 mgblood collection for biological analyses of 30 patients new diagnosis of NVAF (VKA treatment ≤1 week) initiated with apixaban 5 mg |
| Previously diagnosed NVAF: apixaban 5 mg | Other | Drug: Apixaban 5 mgblood collection for biological analyses of 30 patients previously treated by VKA for more than 3 months switched to apixaban 5 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with NVAF (documented by 12 leads ECG or Holter recording) and having one or more factor (s) of risk such as: history of stroke or transient ischemic attack ; age≥75 years; hypertension; diabetes; symptomatic heart failure (NYHA class≥ II) for prevention of cerebral vascular accident and systemic embolism.
- Patients with CHA2DS2-VASc score ≥2
- Patients provided signed written informed consent
- Patients with age≥18 years
- Patients previously treated with VKA or patients newly diagnosed with AF.
Key exclusion criteria (16 listed)
- AF or flutter due to reversible causes according to investigator
- Clinically significant mitral stenosis
- Any other condition than atrial fibrillation that require chronic anticoagulation (prosthetic heart valve or valve repair, venous thromboembolism)
- A need for aspirin at a dose of ≥160 mg a day or for both aspirin and adenosine diphosphate (ADP) inhibitor (clopidogrel, prasugrel or ticagrelor)
- Allergy or adverse reaction to apixaban or any of the excipients
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 |
|---|---|---|
| Apixaban 5 mgAlso: EliquisBood collection for biological analyses at: * inclusion visit * follow-up visit at 1 month * end of research at 3 month | Drug | Newly diagnosed NVAF: apixaban 5 mg, Previously diagnosed NVAF: apixaban 5 mg |
Primary outcome
change from baseline D-dimers level at 3 months.
Time frame: 3 months
D-dimers levels will be determined using an enzyme immunoassay (ELISA method) on citrated plasma.
6 secondary outcomes
Prothrombin fragment F1-F2 measurement
Time frame: at enrollment, at one month, and at three months
von Willebrand factor measurement
Time frame: at enrollment, at one month, and at three months
Thrombin-antithrombin complex measurement
Time frame: at enrollment, at one month, and at three months
High sensitivity CRP measurement
Time frame: at enrollment, at one month, and at three months
Prothrombin time measurement, Activated partial thromboplastin time, and fibrinogen
Time frame: at enrollment, at one month, and at three months
AntiXa apixaban activity measurement
Time frame: at enrollment, at one month, and at three months
Results and safety
The study was stopped early (reason given: not enough patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2024.
- Individual participant dataSharing planned: No
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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.
Ludovic DROUET, MD, PhD study director
Lariboisiere Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Apixaban 5 mg in people with Coagulation Disorder and Non Valvular Atrial Fibrillation, run by Hopital Lariboisière 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 16 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: stopped early, as of the sponsor's last update on 26 Jul 2024. 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.
Are results available for this study?
The study was stopped early (reason given: not enough patients). Results are not available in the source record.
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?
change from baseline D-dimers level at 3 months. (time frame: 3 months). 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 26 Jul 2024.