NCT04073316

AntiCoagulants and COGnition

AntiCoagulants and COGnition (ACCOG Trial): a Single-blind Randomized Controlled Trial Comparing the Neurocognitive Effects of Rivaroxaban Versus Vitamin K Antagonist

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: University Hospital, Angers · Other Government
• Sex: All
• Age: 70 Years
• Healthy volunteers: Not accepted

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 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.

Conditions

• Nonvalvular Atrial Fibrillation

Interventions

Type	Name	Description
DRUG	Rivaroxaban 20 MG	Rivaroxaban intake, 20mg/day
DRUG	Warfarin	Warfarin intake, with target INR range between 2 and 3

Timeline

• Start date: 2020-02-13
• Primary completion: 2023-02-01
• Completion: 2023-02-01
• First posted: 2019-08-29
• Last updated: 2022-07-27

Locations

1 site across 1 country: France