Cryptogenic Ischemic Stroke, Cryptogenic Symptomatic Transient Ischemic Attack
Conditions
Keywords
atrial fibrillation, cryptogenic stroke, continuous monitoring, implantable loop recorder, insertable cardiac monitor
Brief summary
The 2006 American Heart Association / American Stroke Association Council on Stroke Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic recommended that patients with cryptogenic stroke take antithrombotic drugs (i.e. aspirin) in order to prevent a second stroke. When a stroke patient is found to have atrial fibrillation (AF), the guidelines recommend oral anticoagulation due to its superior efficacy over aspirin for stroke prevention. Physicians can best optimize the use of medicines only if they can precisely and correctly diagnose a patient's AF. The purpose of this study is to evaluate the time to first AF by 6 months' continuous rhythm monitoring versus control treatment in subjects with a recent cryptogenic stroke or Transient Ischemic Attack (TIA) without history of AF.
Interventions
DEVICEReveal® XT Insertable Cardiac Monitor
The Insertable Cardiac Monitor is implanted under the skin in the region of the thorax. It continuously monitors the heart's electrical activity for up to three years. ECG data are stored when the device detects a cardiac arrhythmia.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Recent cryptogenic symptomatic transient ischemic attack (TIA) or cryptogenic ischemic stroke.
Exclusion criteria
1. Known etiology of TIA or stroke. 2. Untreated hyperthyroidism. 3. Myocardial infarction less than 1 month prior to stroke or TIA. 4. Coronary bypass grafting less than 1 month prior to stroke or TIA. 5. Valvular disease requiring immediate surgical intervention. 6. History of AF or atrial flutter. 7. Patent Foramen Ovale (PFO) and PFO is or was an indication to start oral anticoagulation (OAC). 8. Permanent indication for OAC at enrollment. 9. Permanent contra-indication for OAC. 10. Included in another clinical trial. 11. Life expectancy less than 1 year. 12. Pregnant. 13. Indicated for Implantable Pulse Generator (IPG), Implantable Cardioverter-Defibrillator (ICD), Cardiac Resynchronization Therapy (CRT) or an implantable hemodynamic monitoring system. 14. Not fit, unable or unwilling to follow the required procedures of the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AF Detection Rate Within 6 Months | 6 months | Percentage of subjects with AF detected within 6 months of follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Recurrent Stroke or TIA (Transient Ischemic Attack) | 12 months | Percentage of subjects with recurrent stroke or TIA within 12 months of follow-up |
| Use of Oral Anticoagulation (OAC) Drugs | 12 months | Percentage of subjects who were using OAC drugs at the 12 months follow-up visit |
| Use of Antiarrhythmic Drugs | 12 months | Percentage of subjects who were using antiarrhythmic drugs at the 12 months follow-up visit |
| AF Detection Rate Within 12 Months | 12 months | Percentage of subjects with AF detected within 12 months of follow-up |
| Clinical Disease Burden and Care Pathway | 12 months | Incidence of cardiovascular (CV) or stroke/TIA related hospitalizations within 12 months |
| Impact of Patient Assistant Use on AF Diagnosis | Follow-up closure | AF detection lag (days from AF occurrence to AF diagnosis) characterized by patient assistant (PA) use frequency |
| Health Outcome as Evaluated by EQ-5D Questionnaire | 12 months | EQ-5D VAS (visual analog scale) quality of life score, which is a continuous measure of quality of life ranging from 0 (worst) to 100 (perfect health). |
Countries
Austria, Belgium, Canada, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Slovakia, Spain, Sweden, United States
Participant flow
Recruitment details
A total of 447 subjects were enrolled in 55 study centers from 14 countries in North America and Europe, during the recruitment period of June 2009 to April 2012.
Pre-assignment details
A total of 6 enrolled subjects were exited from the study prior to randomization due to: Eligibility criteria not met (n=4), and Subject withdrew consent (n=2).
Participants by arm
| Arm | Count |
|---|---|
| Continuous Monitoring Continuous cardiac monitoring by the Reveal® XT Insertable Cardiac Monitor
Reveal® XT Insertable Cardiac Monitor: The Insertable Cardiac Monitor is implanted under the skin in the region of the thorax. It continuously monitors the heart's electrical activity for up to three years. ECG data are stored when the device detects a cardiac arrhythmia. | 221 |
| Control Arm Follow-up at the same frequency, but with no Insertable Cardiac Monitor | 220 |
| Total | 441 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Physician Decision | 3 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 7 |
Baseline characteristics
| Characteristic | Control Arm | Total | Continuous Monitoring |
|---|---|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 11.3 | 61.5 years STANDARD_DEVIATION 11.3 | 61.6 years STANDARD_DEVIATION 11.4 |
| Region of Enrollment Austria | 16 participants | 39 participants | 23 participants |
| Region of Enrollment Belgium | 27 participants | 41 participants | 14 participants |
| Region of Enrollment Canada | 6 participants | 9 participants | 3 participants |
| Region of Enrollment Denmark | 3 participants | 6 participants | 3 participants |
| Region of Enrollment Finland | 2 participants | 2 participants | 0 participants |
| Region of Enrollment France | 17 participants | 34 participants | 17 participants |
| Region of Enrollment Germany | 32 participants | 71 participants | 39 participants |
| Region of Enrollment Greece | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Italy | 31 participants | 59 participants | 28 participants |
| Region of Enrollment Netherlands | 11 participants | 23 participants | 12 participants |
| Region of Enrollment Slovakia | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Spain | 5 participants | 5 participants | 0 participants |
| Region of Enrollment Sweden | 1 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 66 participants | 146 participants | 80 participants |
| Sex: Female, Male Female | 82 Participants | 161 Participants | 79 Participants |
| Sex: Female, Male Male | 138 Participants | 280 Participants | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 41 / 221 | 9 / 220 |
| serious Total, serious adverse events | 68 / 221 | 58 / 220 |
Outcome results
Primary
AF Detection Rate Within 6 Months
Percentage of subjects with AF detected within 6 months of follow-up
Time frame: 6 months
Population: Intention-to-treat (ITT) population (all randomized subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous Monitoring | AF Detection Rate Within 6 Months | 8.9 percentage of participants |
| Control Arm | AF Detection Rate Within 6 Months | 1.4 percentage of participants |
p-value: 0.000695% CI: [1.9, 21.7]Log Rank
Secondary
AF Detection Rate Within 12 Months
Percentage of subjects with AF detected within 12 months of follow-up
Time frame: 12 months
Population: Intention-to-treat (ITT) population (all randomized subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous Monitoring | AF Detection Rate Within 12 Months | 12.4 percentage of participants |
| Control Arm | AF Detection Rate Within 12 Months | 2.0 percentage of participants |
p-value: <0.000195% CI: [2.6, 20.8]Log Rank
Secondary
Clinical Disease Burden and Care Pathway
Incidence of cardiovascular (CV) or stroke/TIA related hospitalizations within 12 months
Time frame: 12 months
Population: Intention-to-treat (ITT) population (all randomized subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous Monitoring | Clinical Disease Burden and Care Pathway | 10.5 percentage of participants |
| Control Arm | Clinical Disease Burden and Care Pathway | 7.2 percentage of participants |
p-value: 0.3395% CI: [0.73, 2.6]Log Rank
Secondary
Health Outcome as Evaluated by EQ-5D Questionnaire
EQ-5D VAS (visual analog scale) quality of life score, which is a continuous measure of quality of life ranging from 0 (worst) to 100 (perfect health).
Time frame: 12 months
Population: Number of subjects who reported EQ-5D VAS score at the 12 months visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous Monitoring | Health Outcome as Evaluated by EQ-5D Questionnaire | 78.9 units on a scale of 0 to 100 | Standard Deviation 15.6 |
| Control Arm | Health Outcome as Evaluated by EQ-5D Questionnaire | 76.3 units on a scale of 0 to 100 | Standard Deviation 16.2 |
p-value: 0.11t-test, 2 sided
Secondary
Impact of Patient Assistant Use on AF Diagnosis
AF detection lag (days from AF occurrence to AF diagnosis) characterized by patient assistant (PA) use frequency
Time frame: Follow-up closure
Population: Number of subjects in the Continuous Monitoring arm who had AF detected by the Insertable Cardiac Monitor (ICM) during the course of the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Continuous Monitoring | Impact of Patient Assistant Use on AF Diagnosis | PA use frequency not reported | 20.0 days from AF occurrence to AF diagnosis | — |
| Continuous Monitoring | Impact of Patient Assistant Use on AF Diagnosis | PA used everyday | 14.0 days from AF occurrence to AF diagnosis | Standard Deviation 35.6 |
| Continuous Monitoring | Impact of Patient Assistant Use on AF Diagnosis | PA used most of the time (5-6 days/week) | 25.0 days from AF occurrence to AF diagnosis | Standard Deviation 31.4 |
| Continuous Monitoring | Impact of Patient Assistant Use on AF Diagnosis | PA used sometimes (3-4 days/week) | 174.8 days from AF occurrence to AF diagnosis | Standard Deviation 235.9 |
| Continuous Monitoring | Impact of Patient Assistant Use on AF Diagnosis | PA used rarely (1-2 days/week) | 15.3 days from AF occurrence to AF diagnosis | Standard Deviation 9.3 |
| Continuous Monitoring | Impact of Patient Assistant Use on AF Diagnosis | PA never used | 92.0 days from AF occurrence to AF diagnosis | — |
Secondary
Incidence of Recurrent Stroke or TIA (Transient Ischemic Attack)
Percentage of subjects with recurrent stroke or TIA within 12 months of follow-up
Time frame: 12 months
Population: Intention-to-treat (ITT) population (all randomized subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous Monitoring | Incidence of Recurrent Stroke or TIA (Transient Ischemic Attack) | 7.1 percentage of participants |
| Control Arm | Incidence of Recurrent Stroke or TIA (Transient Ischemic Attack) | 9.1 percentage of participants |
p-value: 0.2595% CI: [0.35, 1.32]Log Rank
Secondary
Use of Antiarrhythmic Drugs
Percentage of subjects who were using antiarrhythmic drugs at the 12 months follow-up visit
Time frame: 12 months
Population: Number of subjects who completed the 12 months follow-up visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous Monitoring | Use of Antiarrhythmic Drugs | 2.0 percentage of participants |
| Control Arm | Use of Antiarrhythmic Drugs | 1.6 percentage of participants |
95% CI: [-2.3, 3.1]
Secondary
Use of Oral Anticoagulation (OAC) Drugs
Percentage of subjects who were using OAC drugs at the 12 months follow-up visit
Time frame: 12 months
Population: Number of subjects who completed the 12-months follow-up visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuous Monitoring | Use of Oral Anticoagulation (OAC) Drugs | 14.7 percentage of participants |
| Control Arm | Use of Oral Anticoagulation (OAC) Drugs | 6.0 percentage of participants |
95% CI: [2.8, 14.8]