Arrhythmias, Cardiac, Atrial Fibrillation, Stroke
Conditions
Keywords
ischemic stroke, atrial fibrillation, etiologic investigations, secondary prevention, anticoagulation, arrhythmias, embolic stroke, undetermined etiology, implantable loop recorder, external loop recorder
Brief summary
The overall aim of this trial is to determine the most cost effective approach to diagnose paroxysmal atrial fibrillation (PAF) following transient ischemic attack (TIA) and stroke. A summary of the rationale for this study is as follows: 1. Recently completed randomized trials of cardiac monitoring following stroke have established that PAF is more common than previously recognized in cryptogenic stroke. 2. The majority of TIA/stroke patients will have at least one potential stroke mechanism identified by the time etiologic investigations completed. 3. Detecting PAF in patients with strokes with known causes (eg. lacunar and large vessel atherosclerosis) is clinically important since appropriate anticoagulation for AF reduces stroke recurrence in all patients with prior TIA/stroke not just cryptogenic strokes. 4. There are competing technologies for evaluating cardiac rhythm and diagnosing AF but no cost effectiveness data 5. The rates of PAF in strokes with known causes (SKC) have not been well characterized. PER-DIEM is a pilot study to compare two different cardiac monitoring technologies as first-line investigations to detect PAF in patients with recent stroke and TIA. The study will also assess whether a pivotal trial is feasible and warranted. The principal research questions to be addressed in this study will be: 1. Whether implantable loop recorder (ILR) plus remote monitoring will diagnose more paroxysmal AF / atrial flutter and provide a better assessment of the total burden of AF resulting in a greater proportion of patients started on an OAC versus the external loop recorder (ELR) strategy. 2. What is the relative cost-effectiveness as a first-line investigation of long-term implantable ECG (ILR) coupled with remote monitoring for 12 months compared to external event-triggered ECG loop recorder (ELR) for 30 days in the diagnosis clinically actionable AF in following TIA/stroke. 2\) What is the feasibility, patient compliance, diagnostic accuracy and rates of AF detection (\>30 seconds) of ILR compared to the ELR strategies.
Interventions
DEVICEMedtronic Reveal LINQ
DEVICESorin Spiderflash-t
Sponsors
University of Calgary
Alberta Innovates Health Solutions
Medtronic
University of Alberta
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of the index event\* made by a stroke specialist of an acute ischemic stroke or TIA occurring within the previous 90 days. The event must be either: 1. an arterial ischemic stroke confirmed by neuroimaging; or 2. transient ischemic attack with diffusion weighted positive lesion on MRI * At least one 12-lead ECG has already been obtained as part of the routine clinical post-stroke/TIA work-up, and no ECGs have shown any episodes of atrial fibrillation or atrial flutter * The patient is being actively investigated for the etiology of the stroke/TIA event and additional cardiac monitoring is desired to screen further for the possibility of occult paroxysmal atrial fibrillation/flutter * Age 18 years or older * Informed consent from the patient * The patient is expected to survive at least 6 months.
Exclusion criteria
* Any previously documented atrial fibrillation or atrial flutter, i.e. a past history of atrial fibrillation/flutter or atrial fibrillation/flutter detected on ECG, Holter, or telemetry following the index stroke/TIA event (a remote history of transient perioperative atrial fibrillation is not exclusionary) * Planned carotid endarterectomy or carotid artery stenting within 90 days * Any condition for which there is already an indication for long term anticoagulation Pacemaker or implantable cardioverter defibrillator device * Work-up for stroke that has already included extended (\>48 hour) external ECG (excluding telemetry) * Stroke and/or comorbid illness will prevent completion of planned follow-up assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Definite AF or Highly Probable AF | 12 months | Definite AF or highly probable AF (adjudicated new AF lasting ≥2 minutes within 12 months of randomization) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AF Lasting ≥2 Min or Death by 12 Months | 12 months | Detection of atrial fibrillation lasting ≥ 2 minutes or death by 12 months. |
| TIA | 12 months | Transient ischemic attack. |
| Recurrent Stroke | 12 months | Recurrent ischemic stroke. |
| Hemorrhage | 12 months | Intracerebral hemorrhage. |
| Death | 12 months | Participant death. |
| ≥1 Serious Adverse Event | 12 months | Patients with ≥1 serious adverse event. |
| Compliance | 12 months | Compliance with assigned therapy (accept ILR, conduct at least 80% of ELR assessments) |
| Costs of Cardiac and Non-cardiac Investigations | 12 months | Costs for all cardiac and non-cardiac investigations related to etiologic workup of index stroke / TIA. |
| Duration of Any Detected Atrial Fibrillation / Atrial Flutter. | 12 months | Total duration of any detected atrial fibrillation / atrial flutter. |
| Oral Anticoagulation Therapy | 12 months | Initiation of oral anticoagulation therapy in patients with definite AF. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Predictors of AF Detection | 12 months | Association between baseline clinical characteristics (e.g. comorbidities, burden of supraventricular ectopy on Holter, left atrial dimension) and subsequent detection of AF |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Implanted Loop Recorder long-term implantable ECG (Medtronic Reveal LINQ) coupled with remote monitoring (MyCareLink) for 12 months
Medtronic Reveal LINQ | 150 |
| External Loop Recorder external event-triggered ECG loop recorder (Sorin Spiderflash-t) for 30 days
Sorin Spiderflash-t | 150 |
| Total | 300 |
Baseline characteristics
| Characteristic | Implanted Loop Recorder | External Loop Recorder | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 150 Participants | 150 Participants | 300 Participants |
| Age, Continuous | 65.5 years | 63.4 years | 64.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hypertension | 93 Participants | 94 Participants | 187 Participants |
| Previous Stroke | 36 Participants | 34 Participants | 70 Participants |
| Region of Enrollment Canada | 150 participants | 150 participants | 300 participants |
| Sex: Female, Male Female | 61 Participants | 60 Participants | 121 Participants |
| Sex: Female, Male Male | 89 Participants | 90 Participants | 179 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 150 | 3 / 150 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 14 / 150 | 4 / 150 |
Outcome results
Primary
Definite AF or Highly Probable AF
Definite AF or highly probable AF (adjudicated new AF lasting ≥2 minutes within 12 months of randomization)
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Implanted Loop Recorder | Definite AF or Highly Probable AF | 23 Participants |
| External Loop Recorder | Definite AF or Highly Probable AF | 7 Participants |
p-value: 0.00395% CI: [1.45, 7.42]t-test, 2 sided
Secondary
≥1 Serious Adverse Event
Patients with ≥1 serious adverse event.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Implanted Loop Recorder | ≥1 Serious Adverse Event | 14 Participants |
| External Loop Recorder | ≥1 Serious Adverse Event | 4 Participants |
Secondary
AF Lasting ≥2 Min or Death by 12 Months
Detection of atrial fibrillation lasting ≥ 2 minutes or death by 12 months.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Implanted Loop Recorder | AF Lasting ≥2 Min or Death by 12 Months | 26 Participants |
| External Loop Recorder | AF Lasting ≥2 Min or Death by 12 Months | 10 Participants |
p-value: 0.00595% CI: [3.4, 17.9]t-test, 2 sided
Secondary
Compliance
Compliance with assigned therapy (accept ILR, conduct at least 80% of ELR assessments)
Time frame: 12 months
Population: Outcome measure not performed.
Secondary
Costs of Cardiac and Non-cardiac Investigations
Costs for all cardiac and non-cardiac investigations related to etiologic workup of index stroke / TIA.
Time frame: 12 months
Population: Outcome measure not performed.
Secondary
Death
Participant death.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Implanted Loop Recorder | Death | 3 Participants |
| External Loop Recorder | Death | 3 Participants |
95% CI: [-3.2, 3.2]
Secondary
Duration of Any Detected Atrial Fibrillation / Atrial Flutter.
Total duration of any detected atrial fibrillation / atrial flutter.
Time frame: 12 months
Population: Outcome measure not performed.
Secondary
Hemorrhage
Intracerebral hemorrhage.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Implanted Loop Recorder | Hemorrhage | 1 Participants |
| External Loop Recorder | Hemorrhage | 1 Participants |
95% CI: [-1.8, 1.8]
Secondary
Oral Anticoagulation Therapy
Initiation of oral anticoagulation therapy in patients with definite AF.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Implanted Loop Recorder | Oral Anticoagulation Therapy | 23 Participants |
| External Loop Recorder | Oral Anticoagulation Therapy | 7 Participants |
Secondary
Recurrent Stroke
Recurrent ischemic stroke.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Implanted Loop Recorder | Recurrent Stroke | 5 Participants |
| External Loop Recorder | Recurrent Stroke | 8 Participants |
Secondary
TIA
Transient ischemic attack.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Implanted Loop Recorder | TIA | 6 Participants |
| External Loop Recorder | TIA | 2 Participants |
p-value: 0.2895% CI: [-1, 6.3]t-test, 2 sided
Other Pre-specified
Predictors of AF Detection
Association between baseline clinical characteristics (e.g. comorbidities, burden of supraventricular ectopy on Holter, left atrial dimension) and subsequent detection of AF
Time frame: 12 months
Population: Outcome measure not performed