Electronic Monitoring and Improvement of Adherence to DOACs in Polymedicated Stroke Patients (MAAESTRO)

Electronic Monitoring and Improvement of Adherence to Direct Oral Anticoagulant Treatment - a Randomised Crossover Study of an Educational and Reminder-based Intervention in Ischaemic Stroke Patients Under Polypharmacy

Primary objective of the MAAESTRO trial is to evaluate the impact of an educational and reminder-based intervention on the adherence of stroke patients to DOACs. Secondary objectives are to evaluate the association between non-adherence and clinical events, to identify predictors of non-adherence and to compare objective measures of adherence with self-reporting.

Key methodological instrument for this study will be the "Time4Med" pillbox with Smart/ Reminder Card. The study includes 3 visits (baseline visit 0, follow-up visit 1 and end-of-study visit 2) with a total follow-up of 9 months.

After an initial 3-month observational phase with electronic monitoring of adherence using the "Smart Card", all patients will receive counselling based on their electronically recorded drug intake data, as well as a multicompartment pillbox. Patients will be then randomised to one of two groups in a crossover design, so that in the subsequent 6-month interventional phase one group will use a (reminder-delivering) "Reminder Card" for the first 3 months and the "Smart Card" for the last 3 months, while the second group will use the cards in reverse order.

Study Overview

• Status: Completed
• Conditions: Stroke, Ischemic; Adherence, Patient
• Intervention / Treatment: Behavioral: Medication intake reminders; Behavioral: Pillbox use and counselling

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent form (ICF)
• Adult patients (≥ 18 years)
• Hospitalization for acute ischaemic stroke (including TIA with positive neuroimaging)
• DOAC treatment for atrial fibrillation or embolic stroke of undetermined source
• Patients receiving polypharmacy, defined as at least 3 drugs (including DOAC treatment)
• Patients self-administering their medication
• Patients already using a pillbox or willing to use one

Exclusion Criteria:

• Patients not able or unwilling to sign ICF
• Medication administration by caregiver - Filling of the pillbox by a pharmacy, relatives or other caregivers does not exclude the patients, provided that they self-administer their medication
• Patients who are, in the opinion of the investigator, unlikely to adhere to the study schedule or are unsuitable for any other reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group 1; Intake reminders followed by crossover to no intake reminders	Behavioral: Medication intake reminders; Acoustic and visual alarm at predefined DOAC-intake timepoints.; Behavioral: Pillbox use and counselling; All patients will be counselled based on their previous electronically recorded adherence data and will be given a multicompartment pillbox für daily use
Other: Group 2; No intake reminders followed by crossover to intake reminders	Behavioral: Medication intake reminders; Acoustic and visual alarm at predefined DOAC-intake timepoints.; Behavioral: Pillbox use and counselling; All patients will be counselled based on their previous electronically recorded adherence data and will be given a multicompartment pillbox für daily use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of non-optimal timing adherence to DOACs	Non-optimal timing adherence is defined as at least one DOAC dose not recorded or recorded outside of 25% of the prescribed dosing time schedule	0 - 3 months, 3 - 6 months, 6 - 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of non-optimal taking adherence to DOACs	Non-optimal taking adherence to DOACs is defined as at least one DOAC dose not recorded	0 - 3 months, 3 - 6 months, 6 - 9 months
Change of timing adherence to DOACs	Timing adherence to DOACs is defined as the proportion of prescribed DOAC doses taken within 25% of the prescribed dosing time schedule	0 - 3 months, 3 - 6 months, 6 - 9 months
Change of taking adherence to DOACs	Taking adherence to DOACs is defined as the proportion of prescribed DOAC doses taken.	0 - 3 months, 3 - 6 months, 6 - 9 months
Self-reported adherence to DOACs	Self-reported adherence to DOACs is captured on various questionnaires	0 - 6 months
Clinical vascular events or death	Recurrent ischaemic stroke or TIA, intracranial hemorrhage, major extracranial hemorrhage, myocardial infarction, venous thromboembolism and death	up to 9 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: University of Basel; Clinical Trial Unit, University Hospital Basel, Switzerland
• Investigators: Principal Investigator: Philippe A Lyrer, MD, University Hospital Basel, Stroke Center and Department of Neurology; Principal Investigator: Kurt Hersberger, MSc, PhD, University of Basel, Department of Pharmaceutical Sciences

Publications and helpful links

General Publications

• Dietrich F, Polymeris AA, Verbeek M, Engelter ST, Hersberger KE, Schaedelin S, Arnet I, Lyrer PA. Impact of the COVID-19 lockdown on the adherence of stroke patients to direct oral anticoagulants: a secondary analysis from the MAAESTRO study. J Neurol. 2022 Jan;269(1):19-25. doi: 10.1007/s00415-021-10631-5. Epub 2021 Jun 3.
• Albert V, Polymeris AA, Dietrich F, Engelter ST, Hersberger KE, Schaedelin S, Lyrer PA, Arnet I. Insights Into Direct Oral Anticoagulant Therapy Implementation of Stroke Survivors with Atrial Fibrillation in an Ambulatory Setting. J Stroke Cerebrovasc Dis. 2021 Feb;30(2):105530. doi: 10.1016/j.jstrokecerebrovasdis.2020.105530. Epub 2020 Dec 14.
• Polymeris AA, Albert V, Hersberger KE, Engelter ST, Schaedelin S, Arnet I, Lyrer PA. Protocol for MAAESTRO: Electronic Monitoring and Improvement of Adherence to Direct Oral Anticoagulant Treatment-A Randomized Crossover Study of an Educational and Reminder-Based Intervention in Ischemic STROke Patients Under Polypharmacy. Front Neurol. 2018 Dec 21;9:1134. doi: 10.3389/fneur.2018.01134. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Actual): March 14, 2022
• Study Completion (Actual): March 14, 2022

Study Registration Dates

• First Submitted: November 9, 2017
• First Submitted That Met QC Criteria: November 14, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Estimate): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: ischemic stroke, direct oral anticoagulants, adherence, electronic monitoring, adherence-improving intervention, polypharmacy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia
• Other Study ID Numbers: me17Lyrer2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No