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Trial record 23 of 157 for:    warfarin AND Vitamin K

AntiCoagulants and COGnition (ACCOG)

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ClinicalTrials.gov Identifier: NCT04073316
Recruitment Status : Not yet recruiting
First Posted : August 29, 2019
Last Update Posted : August 29, 2019
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
University Hospital, Angers

Brief 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).

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 volumetric changes of the brain after 26 and 52 weeks of intervention
  • the changes of independence and autonomy after 26 and 52 weeks of intervention
  • the changes of serum vitamin K concentration after 26 and 52 weeks of intervention

Condition or disease Intervention/treatment Phase
Nonvalvular Atrial Fibrillation Drug: Rivaroxaban 20 MG Drug: Warfarin Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: AntiCoagulants and COGnition (ACCOG Trial): a Single-blind Randomized Controlled Trial Comparing the Neurocognitive Effects of Rivaroxaban Versus Vitamin K Antagonist
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: "Intervention" group Drug: Rivaroxaban 20 MG
Rivaroxaban intake, 20mg/day

Active Comparator: "Control" group Drug: Warfarin
Warfarin intake, with target INR range between 2 and 3




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. Change in executive functions [ Time Frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion. ]
    Executive functions are assessed with Frontal Assessment Battery score (FAB).

  2. Change in executive functions [ Time Frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion. ]
    Executive functions are assessed with digit spans.

  3. Change in executive functions [ Time Frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion. ]
    Executive functions are assessed with Trail Making Tests (TMT) parts A and B.

  4. Change in executive functions [ Time Frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion. ]
    Executive functions are assessed with Stroop test.

  5. Change in executive functions [ Time Frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion. ]
    Executive functions are assessed with the Processing Speed Index.

  6. Change in episodic memory [ Time Frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion. ]
    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.

  7. Change in the volume and subvolumes of the brain [ Time Frame: This outcome is assessed at baseline and 52 weeks after inclusion ]
    The volume and subvolumes of the brain are measured with MRI (FreeSurfer).

  8. Change in independence and autonomy [ Time Frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion. ]

    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.


  9. Change in independence and autonomy [ Time Frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion. ]

    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.


  10. Change in serum concentration of vitamin K [ Time Frame: This outcome is assessed at baseline, 26 and 52 weeks after inclusion. ]
    Serum concentration of vitamin K is assessed with a blood sampling.



Information from the National Library of Medicine

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Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 ≥ 25
  • Subjects who can give written consent to participate in the study
  • Affiliation to French Social Security.

Exclusion Criteria:

  • Known history of stroke and/or a diagnosed condition of dementia (DSM-IV criteria) and/or severe depressive symptomatology (score on the 15-item Geriatric Depression Scale > 10)
  • Moderate or severe mitral stenosis
  • Conditions other than NVAF that require anticoagulation
  • Use of anticoagulant 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
  • 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
  • Any contraindication to MRI
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04073316


Contacts
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Contact: Cédric ANNWEILER, MD, PhD +33 2 41 35 54 86 cedric.annweiler@chu-angers.fr

Locations
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France
Angers University Hospital Not yet recruiting
Angers, France, 49933 cedex 9
Contact: Cédric ANNWEILER, MD, PhD    +33 2 41 35 47 25    cedric.annweiler@chu-angers.fr   
Principal Investigator: Cédric ANNWEILER, MD, PhD         
Sponsors and Collaborators
University Hospital, Angers
Bayer

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Responsible Party: University Hospital, Angers
ClinicalTrials.gov Identifier: NCT04073316     History of Changes
Other Study ID Numbers: 2019-000794-23
First Posted: August 29, 2019    Key Record Dates
Last Update Posted: August 29, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Warfarin
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Rivaroxaban
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action