Nonvalvular Atrial FibrillationPhase 4ACCOGNCT04073316
AntiCoagulants and COGnition
A Phase 4 study testing Rivaroxaban 20 MG and Warfarin in people with Nonvalvular Atrial Fibrillation, run by University Hospital, Angers at 1 site in France.
Trial summary
The purpose of this study is to compare the change of global cognitive performance after 52 weeks of intervention among participants with nonvalvular atrial fibrillation (NVAF) receiving rivaroxaban versus a vitamin K antagonist (warfarin). Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Nonvalvular Atrial Fibrillation
- What is being tested?
- Rivaroxaban 20 MG and Warfarin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteFrance
- Study dates
- 13 Feb 2020to Feb 2023
- 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 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Men or women ≥ 70 years old
- Newly diagnosed hemodynamically stable NVAF longer than 52 hours or of unknown duration, and CHA2DS2-VASc score according to ESC 2016 guidelines for anticoagulation treatment indications
- MMSE score ≥ 20
- Subjects who can give written consent to participate in the study
- Affiliation to a social security scheme.
Who cannot join
- Known history of stroke and/or a diagnosed condition of dementia (DSM-IV criteria) and/or severe depressive symptomatology (score on the 4-item Geriatric Depression Scale > 3)
- Moderate or severe mitral stenosis
- Conditions other than NVAF that require anticoagulation
- Use of anticoagulant more than 3 days at inclusion or more than 15 days in the preceding 12 months
- Regular use of antiplatelet medications and/or nonsteroidal anti-inflammatory agents and/or azole class of antifungal agents and/or inhibitor of HIV protease
- Acute thromboembolic events or thrombosis (venous/arterial) within the last 14 days prior to randomization
Show all 13Show fewer
- Known presence of cardiac thombus or myxoma or valvular atrial fibrillation
- Any contraindication to anticoagulation, high risk of bleeding, and any other contraindication listed in the local labeling for the experimental treatment and comparator treatment
- Unstable health, severe hepatic failure, or severe and moderate renal failure (creatinine clearance <50 mL/min), acute coronary syndromes
- Participation in another simultaneous clinical trial
- Inability to understand and speak French
- Refusal to participate from the participant
- Persons deprived of their liberty by administrative or judicial decision, persons under psychiatric care under duress, adults subject to a legal protection measure or unable to express their consent
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Angers University Hospital
Angers, 49933 cedex 9
Cédric ANNWEILER, MD, PhD, +33 2 41 35 47 25, cedric.annweiler@chu-angers.fr
Cédric ANNWEILER, MD, PhD
About this study
Official title: AntiCoagulants and COGnition (ACCOG Trial): a Single-blind Randomized Controlled Trial Comparing the Neurocognitive Effects of Rivaroxaban Versus Vitamin K Antagonist
The purpose of this study is to compare the change of global cognitive performance after 52 weeks of intervention among participants with nonvalvular atrial fibrillation (NVAF) receiving rivaroxaban versus a vitamin K antagonist (warfarin).
The secondary objectives are to compare, among participants with NVFA receiving rivaroxaban versus warfarin :
- the changes of global cognitive performance after 26 weeks of intervention
- the changes of executive functions after 26 and 52 weeks of intervention
- the changes of episodic memory after 26 and 52 weeks of intervention
- the changes of independence and autonomy after 26 and 52 weeks of intervention
Read the detailed description
Detailed Description:
Vitamin K antagonists (VKAs) are commonly used for their role in hemostasis by interfering with vitamin K cycle decreasing the bioavailability of the vitamin K active form. In addition to a role in blood coagulation, vitamin K participates in brain health and function by regulating the synthesis of sphingolipids, a constituent of the myelins sheath and the neurons membrane, and through the biological activation of vitamin K-dependent proteins (VKDPs) involved in neuron survival. Epidemiological studies have reported a positive association between higher serum vitamin K concentration and better verbal episodic memory performance in older adults, and an inverse association between dietary vitamin K intakes and behavioural disorders and cognitive complaint. The clinical implication is that the use of VKAs, which deplete the active form of vitamin K, may be responsible for Central Nervous System (CNS) disorders.
CNS abnormalities were observed in newborns exposed in utero to VKA. Similarly, the investigators and other researchers reported that the use of VKAs (especially fluindione) was directly associated with cognitive decline (notably executive dysfunction) and hippocampal atrophy in older adults, even while taking into account the history of atrial fibrillation, stroke and vascular brain changes. These cross-sectional and longitudinal studies were yet limited by their observational design. Clinical trials are now warranted to explore the effect on cognition of VKAs against direct oral anticoagulants (DOACs), whose indications are similar but whose mechanism does not interfere with vitamin K. The favorable impact of the use of DOACs compared to VKA in the incidence of dementia was also observed in a US retrospective population-based study of patients managed per routine clinical care.
The investigators hypothesize that VKAs have a deleterious impact on cognition and brain morphology compared to DOACs, due to the decrease in vitamin K bioavailability. A review of the published clinical trials comparing the effects of VKAs and DOACs, especially rivaroxaban, shows that cognition and brain volume were not assessed as outcomes in these trials.
- Conditions
- Nonvalvular Atrial Fibrillation
- Being tested
- Rivaroxaban 20 MG, Warfarin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rivaroxaban 20 MGDrug
Rivaroxaban intake, 20mg/day
WarfarinDrug
Warfarin intake, with target INR range between 2 and 3
| Study group | Role | What they receive |
|---|---|---|
| "Intervention" group | Experimental | Not described Receives: Drug: Rivaroxaban 20 MG |
| "Control" group | Active comparator | Not described Receives: Drug: Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in global cognitive performance
Global cognitive performance is assessed with Alzheimer's Disease Assessment Scale-cognition score (ADAS-cog).
Total scores range from 0-70, with higher scores (≥ 18) indicating greater cognitive impairment.
Measured: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Secondary outcomes (8)
Change in executive functions
Executive functions are assessed with Frontal Assessment Battery score (FAB).
Measured: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in executive functions
Executive functions are assessed with digit spans.
Measured: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in executive functions
Executive functions are assessed with Trail Making Tests (TMT) parts A and B.
Measured: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in executive functions
Executive functions are assessed with Stroop test.
Measured: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in executive functions
Executive functions are assessed with the Processing Speed Index.
Measured: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in episodic memory
Episodic memory is assessed with Five-word test. The 5-word test studies the recall of a short list. The score of the first immediate recall and the score of the delayed recall should normally be equal to 10.
Measured: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in independence and autonomy
Independence and autonomy are assessed with Activities of Daily Living (ADL) score.
ADL is an autonomy assessment grid (from 0 to 6) for basic activities of daily living (ADL).
The lower the score, the more dependent the patient is.
Measured: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in independence and autonomy
Independence and autonomy are assessed with the 4-item Instrumental Activities of Daily Living (IADL-PAQUID) score.
This test is used to assess the level of dependence in instrumental activities of daily living.
The scale ranges from 0 to 4, with 0 indicating total dysautonomy and 4 indicating a totally autonomous person.
Measured: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2019
- Study start13 Feb 2020
- Primary completionFeb 2023 (estimated)
- Study completionFeb 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonvalvular Atrial FibrillationStudies 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
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Collaborators
- Bayer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04073316
- Sponsor's protocol ID
- 2019-000794-23
- Other IDs
- 2019
- Acronym
- ACCOG
- Status last verified
- Jul 2022
- First submitted
- 26 Aug 2019
- Last updated
- 27 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AntiCoagulants and COGnition (ACCOG Trial): a Single-blind Randomized Controlled Trial Comparing the Neurocognitive Effects of Rivaroxaban Versus Vitamin K Antagonist
- ClinicalTrials.gov ID
- NCT04073316
- Acronym / sponsor ID
- ACCOG / 2019-000794-23
- Conditions
- Nonvalvular Atrial Fibrillation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- University Hospital, AngersOther government
- Collaborators
- Bayer
- Study start
- 13 Feb 2020 (actual)
- Primary completion
- Feb 2023 (estimated)
- Study completion
- Feb 2023 (estimated)
- First posted
- 29 Aug 2019 (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.
The purpose of this study is to compare the change of global cognitive performance after 52 weeks of intervention among participants with nonvalvular atrial fibrillation (NVAF) receiving rivaroxaban versus a vitamin K antagonist (warfarin).
The secondary objectives are to compare, among participants with NVFA receiving rivaroxaban versus warfarin :
- the changes of global cognitive performance after 26 weeks of intervention
- the changes of executive functions after 26 and 52 weeks of intervention
- the changes of episodic memory after 26 and 52 weeks of intervention
- the changes of independence and autonomy after 26 and 52 weeks of intervention
Detailed description
Detailed Description:
Vitamin K antagonists (VKAs) are commonly used for their role in hemostasis by interfering with vitamin K cycle decreasing the bioavailability of the vitamin K active form. In addition to a role in blood coagulation, vitamin K participates in brain health and function by regulating the synthesis of sphingolipids, a constituent of the myelins sheath and the neurons membrane, and through the biological activation of vitamin K-dependent proteins (VKDPs) involved in neuron survival. Epidemiological studies have reported a positive association between higher serum vitamin K concentration and better verbal episodic memory performance in older adults, and an inverse association between dietary vitamin K intakes and behavioural disorders and cognitive complaint. The clinical implication is that the use of VKAs, which deplete the active form of vitamin K, may be responsible for Central Nervous System (CNS) disorders.
CNS abnormalities were observed in newborns exposed in utero to VKA. Similarly, the investigators and other researchers reported that the use of VKAs (especially fluindione) was directly associated with cognitive decline (notably executive dysfunction) and hippocampal atrophy in older adults, even while taking into account the history of atrial fibrillation, stroke and vascular brain changes. These cross-sectional and longitudinal studies were yet limited by their observational design. Clinical trials are now warranted to explore the effect on cognition of VKAs against direct oral anticoagulants (DOACs), whose indications are similar but whose mechanism does not interfere with vitamin K. The favorable impact of the use of DOACs compared to VKA in the incidence of dementia was also observed in a US retrospective population-based study of patients managed per routine clinical care.
The investigators hypothesize that VKAs have a deleterious impact on cognition and brain morphology compared to DOACs, due to the decrease in vitamin K bioavailability. A review of the published clinical trials comparing the effects of VKAs and DOACs, especially rivaroxaban, shows that cognition and brain volume were not assessed as outcomes in these trials.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| "Intervention" group | Experimental | Drug: Rivaroxaban 20 MG |
| "Control" group | Active comparator | Drug: Warfarin |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- Men or women ≥ 70 years old
- Newly diagnosed hemodynamically stable NVAF longer than 52 hours or of unknown duration, and CHA2DS2-VASc score according to ESC 2016 guidelines for anticoagulation treatment indications
- MMSE score ≥ 20
- Subjects who can give written consent to participate in the study
- Affiliation to a social security scheme.
Key exclusion criteria (13 listed)
- Known history of stroke and/or a diagnosed condition of dementia (DSM-IV criteria) and/or severe depressive symptomatology (score on the 4-item Geriatric Depression Scale > 3)
- Moderate or severe mitral stenosis
- Conditions other than NVAF that require anticoagulation
- Use of anticoagulant more than 3 days at inclusion or more than 15 days in the preceding 12 months
- Regular use of antiplatelet medications and/or nonsteroidal anti-inflammatory agents and/or azole class of antifungal agents and/or inhibitor of HIV protease
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 20 MGRivaroxaban intake, 20mg/day | Drug | "Intervention" group |
| WarfarinWarfarin intake, with target INR range between 2 and 3 | Drug | "Control" group |
Primary outcome
Change in global cognitive performance
Time frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Global cognitive performance is assessed with Alzheimer's Disease Assessment Scale-cognition score (ADAS-cog). Total scores range from 0-70, with higher scores (≥ 18) indicating greater cognitive impairment.
8 secondary outcomes
Change in executive functions
Time frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in executive functions
Time frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in executive functions
Time frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in executive functions
Time frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in executive functions
Time frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in episodic memory
Time frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in independence and autonomy
Time frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Change in independence and autonomy
Time frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2022.
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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.
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 20 MG and Warfarin in people with Nonvalvular Atrial Fibrillation, run by University Hospital, Angers 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 13 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 27 Jul 2022. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cédric ANNWEILER, MD, PhD (+33 2 41 35 54 86, cedric.annweiler@chu-angers.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in global cognitive performance (time frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion.). 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 27 Jul 2022.