Stroke is one of the leading causes behind death and permanent disability in adults. Atrial
      fibrillation (AF) is the most common clinical arrhythmia and its prevalence is steeply
      increasing with age. Atrial fibrillation is associated with a manifold increase in the risk
      for stroke.

      It is considered important to investigate the heart rhythm in stroke survivors without
      previously known AF, because detection of AF will prompt a change in antithrombotic treatment
      with subsequent lowering of the risk of recurrent stroke.

      There are so far very few studies on the prognostic impact of ECG investigations post stroke.
      Despite this knowledge gap, ECG investigation post stroke is given high priority in national
      and international guidelines.

      Considerable clinical resources are currently invested in these ECG investigations without
      knowledge of its utility.

      The investigators plan a nationwide, randomised, register-based study (RRCT) including
      patients aged at least 70 years receiving in-hospital care for stroke or TIA (Transient
      Ischemic Attack). Included patients will be randomised to standard investigation (1-2 days of
      ECG ) or extended ECG investigation (14 days of ECG performed at least twice). Patients
      diagnosed AF will be offered anticoagulation treatment. Long-term follow-up will be performed
      via swedish health care registers.

      The result of this trial will have major impact on the ECG screening recommendations for
      patients who have had stroke, a large group of patients with dismal prognosis.

Atrial Fibrillation Screening Post Ischemic Cerebrovascular Events

Ischemic Stroke

Purpose and aims

      The purpose of the trial is to study the prognostic impact of ECG investigation after stroke
      or TIA.

      The aim is to investigate if extended ECG screening after stroke as compared to standard ECG
      screening reduces the occurrence of the primary composite endpoint of stroke, death and
      intracranial bleeding in patients with stroke or transient ischemic attack (TIA). Secondary
      aims include effects on major bleeding, myocardial infarction, pacemaker implantation, atrial
      fibrillation prevalence, oral anticoagulation (OAC) treatment and cost effectiveness.

      Survey of the field Ischemic stroke is one of the leading causes of mortality worldwide, and
      a major cause behind permanent disability in adults. Atrial fibrillation (AF) is the most
      prevalent permanent clinically relevant arrhythmia with a steeply increasing incidence with
      advancing age. Atrial fibrillation is also one of the strongest risk factors for stroke. The
      increased stroke risk associated with AF can be markedly reduced by OAC treatment.

      Unfortunately, AF is paroxysmal and asymptomatic in a significant proportion of patients,
      leading to lower detection rates and a similar proportion of stroke survivors with an
      untreated risk factor and higher risk of stroke recurrence. For this reason, it is widely
      recommended to make ECG recordings in patients suffering from stroke and TIA in order to
      detect previously undiagnosed AF.

      Despite this, no study so far has been reported to bring evidence on the benefit of ECG AF
      screening in terms of reduced stroke recurrence and mortality after a stroke event. However,
      several studies have reported the yield of new AF diagnosis in stroke/TIA patients using
      different ECG recording strategies in different populations.

      The knowledge gap on the possible benefits and cost effectiveness of ECG investigation after
      stroke/TIA has led to a large variation in international recommendations, a situation
      bringing uncertainty among policy makers, the profession and patients. The variation in
      recommendations from different societies have unusual proportions. There is also a large
      variation in clinical practice between different stroke units in Sweden.

      Furthermore, since the magnitude of the net benefit (or net harm) of the ECG investigation is
      not yet known, extensive clinical resources as well as patient effort are today put into
      these ECG investigations without knowing about the benefit for the patient or cost
      effectiveness.

      Research Idea

      The study will compare current standard ECG investigation after stroke/TIA with an extended
      ECG investigation strategy and compare long-term prognosis in terms of hard clinical
      endpoints among participants.

      P: Patients aged at least 70 years treated in Swedish stroke units for ischemic stroke/TIA
      who after 24-48 hours of standard ECG investigation have shown no signs of atrial
      fibrillation

      I: Extended ECG ambulatory recording, at least 2 separate recordings of 14 days each 2-4
      months apart

      C: standard Swedish ECG investigation, continuous ECG for 24-48 hours

      O: Composite endpoint of recurrent stroke, all-cause mortality and intracerebral bleeding

      For the year 2020, the mean age of Swedish stroke patients was 75 years, with a higher mean
      age among women. Incidence of AF is strongly related to age as confirmed in epidemiological
      studies and in screening studies. The selected cut-off age of 70 years for this study will
      include three fourths of stroke patients targeting those at highest risk for AF. However,
      higher age implies a risk for lower compliance to ECG recordings. This has been taken into
      account when choosing ECG device. Hence, the chosen cut-off age for inclusion is deemed to
      balance the yield of the ECG investigation, the benefit from OAC treatment and stroke risk if
      AF is detected and the expected level of compliance to procedures and treatment related to
      the study.

      The ECG investigation in the control arm is based on the minimum recommendations for stroke
      care issued by the Swedish board of health and welfare. There are however several guidelines
      from international societies recommending higher ambitions for this investigation, i.e longer
      ECG recordings. Several Swedish stroke units are implementing ECG investigations after
      stroke/TIA with ambitions higher than those stated by national minimum recommendations,
      assuming that these investigations will give more benefit to the patient. The study design is
      calculated to give a marked difference between the control and intervention groups to
      overcome the possible problem with an underpowered result reported from a previous study in
      the field.

      Plans and methods for pilot study The pilot study will engage five to six patient-including
      stroke units which are already recruited. The pilot study is planned to include 200-300
      patients with the aim to evaluate feasibility of study management, patient inclusion,
      inclusion rate, ECG recordings, flow of ECG data and short-term follow-up of positive ECG
      findings.

      Parallel to the pilot study, a comprehensive, digital survey on ECG investigation practice
      covering all Swedish stroke units will be undertaken. This survey will be sent to the stroke
      units commencing in september 2021. The outcome of the survey will give a complete and
      up-to-date view of clinical practice and a possibility to identify suitable sites for the
      main trial.

      During 2020, there were 28 000 patients included in national stroke register for stroke or
      TIA and three fourths of these patients were aged 70 years or older. The pilot and main study
      are planned to include 3300 patients during 2021-2024.

Extended ECG investigation

A Multicenter, National, Investigator-initiated, Randomized, Parallel-group, Registerbased Superiority Study to Compare Extended ECG Monitoring Versus Standard ECG Monitoring of 1-2 Days in Elderly Patients With Ischemic Stroke or TIA.

Stroke is defined as the occurence of International Classification of Diseases (ICD) 10 codes I63 in swedish health care registers. Intracranial bleeding is defined as the occurence of ICD 10 codes I61 in swedish health care registers. Mortality is defined as death reported by the swedish registers on cause of death.

Associate Professor, Senior consultant

Stroke is defined as the occurence of ICD 10 codes I63 in swedish health care registers. Intracranial bleeding is defined as the occurence of ICD 10 codes I61 in swedish health care registers. Mortality is defined as death reported by the swedish registers on cause of death.

Defined as the occurence of any of the following ICD 10 codes in swedish health care registers: I60, I62, I850, I983, K250, K252, K254, K256, K260, K262, K264, K266, K270, K272, K274, K276, K280, K284, K286, K290, K625, K661, K920-921, K922, N02, R04, R58, T810, D629, D50-64,D65-69

Defined as the occurence of any of the following ICD 10 codes in swedish health care registers: I21

Defined as the occurence of any of the following measures in swedish health care registers: FPE00-96

Defined as the occurence of any of the following ICD 10 codes in swedish health care registers: Z921 or the prescription of any of the following Anatomical Therapeutic Chemical Classification System (ATC) codes: B01AA, B01AE, B01AF

The proportion of participants with the ICD 10 code I48 in swedish health care registers divided by the total number of participants.

For each participant, the duration of the actual ECG signal acquired during long-term ECG recording will be divided by the theoretical maximum duration of ECG signal which is 14 days. The resulting proportion is the adherence.
Example: A participant discontinues the ECG recording after 7 days and the investigators will receive 7 days of ECG of the expected 14 days of ECG signal for interpretation. In this case, adherence will be 7/14 = 50%.

The incidence of atrioventricular block degree 2 or 3, ventricular tachycardia, >5% premature ventricular ectopic beats, pauses > 3 seconds and bradycardia slower than 40/min and during long-term ECG recording.

Participants will undergo 0-48 hours of continuous ECG recording and at least two long-term continuous ambulatory ECG recordings with a duration of 14 days each.

Participants will undergo 24-48 hours of continuous ECG recording.

Atrial Fibrillation Screening Post Ischemic Cerebrovascular Events

About this trial

Study ID

Status

Type

Phase

Placebo

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Trial Timing

What is this trial about?

What are the participation requirements?

Locations

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