Trial Outcomes & Findings for REVEAL AF: Incidence of AF in High Risk Patients (NCT NCT01727297)

Last Updated: 2018-04-30

Results Overview

Incidence of adjudicated AF lasting six or more minutes at 18 months. Each arrhythmic episode detected by the patient's Reveal device will be reviewed to determine if it is 1) an actual atrial fibrillation episode, and (2) is at least 6 minutes in duration. The first such episode per patient occurring within 18 months will be utilized to determine the 18 month incidence rate.

Recruitment status

COMPLETED

Study phase

Target enrollment

446 participants

Primary outcome timeframe

Implant to 18 months post device insertion

Results posted on

2018-04-30

Participant Flow

Patients in the 'No Reveal Implantable Cardiac Monitor Implant Attempt' arm were exited from the study prior to an implant attempt. Therefore, no outcome data are available. Baseline data are not presented due to variable data collection before the time of exit. Adverse event data were collected for this cohort, and are reported below.

Participant milestones

Participant milestones
Measure	Reveal Implantable Cardiac Monitor Implant Attempted Enrolled subjects who had a Reveal Implantable Cardiac Monitor implant attempt (i.e. underwent the procedure to have a Reveal device implanted)	No Reveal Implantable Cardiac Monitor Implant Attempt Enrolled subjects who exited the study prior to undergoing a procedure to implant a Reveal Implantable Cardiac Monitor
Overall Study STARTED	395	51
Overall Study COMPLETED	293	0
Overall Study NOT COMPLETED	102	51

Reasons for withdrawal

Reasons for withdrawal
Measure	Reveal Implantable Cardiac Monitor Implant Attempted Enrolled subjects who had a Reveal Implantable Cardiac Monitor implant attempt (i.e. underwent the procedure to have a Reveal device implanted)	No Reveal Implantable Cardiac Monitor Implant Attempt Enrolled subjects who exited the study prior to undergoing a procedure to implant a Reveal Implantable Cardiac Monitor
Overall Study Death	13	0
Overall Study Protocol Violation	1	10
Overall Study Adverse Event	3	1
Overall Study Lost to Follow-up	11	0
Overall Study Withdrawal by Subject	26	27
Overall Study Physician Decision	19	5
Overall Study Other (e.g. AF detection pre-implant)	29	8

Baseline Characteristics

REVEAL AF: Incidence of AF in High Risk Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Reveal Implantable Cardiac Monitor Implant Attempted n=395 Participants Enrolled subjects who had a Reveal Implantable Cardiac Monitor implant attempt (i.e. underwent the procedure to have a Reveal device implanted)
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	88 Participants n=5 Participants
Age, Categorical >=65 years	307 Participants n=5 Participants
Age, Continuous	71.6 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	188 Participants n=5 Participants
Sex: Female, Male Male	207 Participants n=5 Participants
Region of Enrollment Austria	18 participants n=5 Participants
Region of Enrollment Netherlands	6 participants n=5 Participants
Region of Enrollment United States	302 participants n=5 Participants
Region of Enrollment Italy	19 participants n=5 Participants
Region of Enrollment Slovenia	4 participants n=5 Participants
Region of Enrollment Germany	39 participants n=5 Participants
Region of Enrollment Spain	7 participants n=5 Participants

PRIMARY outcome

Timeframe: Implant to 18 months post device insertion

Population: This analysis only included patients who received an implantable cardiac monitor, met all inclusion/exclusion criteria, and had device data available. Of the 395 participants who underwent an implant attempt, 1 attempt was unsuccessful, 7 subjects did not meet all inclusion/exclusion criteria, and 2 subjects had no post-implant device data.

Outcome measures

Outcome measures
Measure	Primary Objective Analysis Cohort n=385 Participants Subjects successfully implanted with a Reveal Implantable Cardiac Monitor (ICM), who also (1) have post-implant device data to evaluate, (2) were not on anti-arrhythmic medication at enrollment, (3) did not have AF prior to Reveal ICM implant, and (4) satisfy the Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack (TIA) or thromboembolism (doubled) (CHADS2) inclusion criteria for the study (CHADS2 score of 3 or higher, or a CHADS2 score of 2 along with chronic obstructive pulmonary disease, sleep apnea, renal impairment, or coronary artery disease)	AF Predictors Analysis Cohort: No AF Episodes Subjects successfully implanted with a Reveal Implantable Cardiac Monitor (ICM), and who (1) have post-implant ICM device data to evaluate, (2) were not on anti-arrhythmic medication at enrollment, (3) did not have AF prior to Reveal implant, and (4) did not experience an AF episode lasting at least 6 minutes during follow-up.	Third Visit With AF Detected Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 3rd follow-up visit in which new AF episodes were diagnosed	Fourth Visit With AF Detected Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 4th follow-up visit in which new AF episodes were diagnosed	Fifth Visit With AF Detected Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 5th follow-up visit in which new AF episodes were diagnosed	Sixth Visit With AF Detected Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 6th follow-up visit in which new AF episodes were diagnosed
18 Month Incidence Rate of Atrial Fibrillation (AF) Lasting Six or More Minutes	29.3 percent of participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Time from implant to date of last stored available device data (maximum of 30 months)

Population: This analysis only included patients who received an implantable cardiac monitor, were not on antiarrhythmic medications at baseline, and had device data available. Of the 395 participants who underwent an implant attempt, 1 attempt was unsuccessful, 1 subject was on antiarrhythmic medication, and 2 subjects had no post-implant device data.

AF will be defined as in the primary outcome. Baseline characteristics including demographics, medical history, and biomarkers at enrollment will be tested for their association with a patient's risk of developing AF.

Outcome measures

Outcome measures
Measure	Primary Objective Analysis Cohort n=130 Participants Subjects successfully implanted with a Reveal Implantable Cardiac Monitor (ICM), who also (1) have post-implant device data to evaluate, (2) were not on anti-arrhythmic medication at enrollment, (3) did not have AF prior to Reveal ICM implant, and (4) satisfy the Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack (TIA) or thromboembolism (doubled) (CHADS2) inclusion criteria for the study (CHADS2 score of 3 or higher, or a CHADS2 score of 2 along with chronic obstructive pulmonary disease, sleep apnea, renal impairment, or coronary artery disease)	AF Predictors Analysis Cohort: No AF Episodes n=261 Participants Subjects successfully implanted with a Reveal Implantable Cardiac Monitor (ICM), and who (1) have post-implant ICM device data to evaluate, (2) were not on anti-arrhythmic medication at enrollment, (3) did not have AF prior to Reveal implant, and (4) did not experience an AF episode lasting at least 6 minutes during follow-up.	Third Visit With AF Detected Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 3rd follow-up visit in which new AF episodes were diagnosed	Fourth Visit With AF Detected Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 4th follow-up visit in which new AF episodes were diagnosed	Fifth Visit With AF Detected Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 5th follow-up visit in which new AF episodes were diagnosed	Sixth Visit With AF Detected Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 6th follow-up visit in which new AF episodes were diagnosed
Predictors of the Incidence of AF Gender (Male)	67 Participants	138 Participants	—	—	—	—
Predictors of the Incidence of AF Diabetes	80 Participants	168 Participants	—	—	—	—
Predictors of the Incidence of AF Heart failure	31 Participants	50 Participants	—	—	—	—
Predictors of the Incidence of AF Hypertension	122 Participants	244 Participants	—	—	—	—
Predictors of the Incidence of AF Renal impairment	60 Participants	106 Participants	—	—	—	—
Predictors of the Incidence of AF Chronic obstructive pulmonary disorder	19 Participants	57 Participants	—	—	—	—
Predictors of the Incidence of AF Prior stroke > 1 year ago	23 Participants	56 Participants	—	—	—	—
Predictors of the Incidence of AF Coronary artery disease	75 Participants	157 Participants	—	—	—	—
Predictors of the Incidence of AF Sleep apnea	28 Participants	75 Participants	—	—	—	—
Predictors of the Incidence of AF Family history of AF	5 Participants	3 Participants	—	—	—	—
Predictors of the Incidence of AF Vascular disease	25 Participants	54 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Time from first identified episode of AF to study exit (maximum of 30 months)

Population: Each visit represents the number of subjects who had a 1st, 2nd, 3rd visit, etc. in which AF was identified by the physician. Subjects in the "Sixth Visit with AF Detected" column had 6 visits in which AF was detected by the physician, and the column reflects the actions taken at that sixth visit.

Clinical actions taken in response to clinician awareness of a patient's AF onset or progression will be summarized

Outcome measures

Outcome measures
Measure	Primary Objective Analysis Cohort n=85 Actions at Visits Subjects successfully implanted with a Reveal Implantable Cardiac Monitor (ICM), who also (1) have post-implant device data to evaluate, (2) were not on anti-arrhythmic medication at enrollment, (3) did not have AF prior to Reveal ICM implant, and (4) satisfy the Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack (TIA) or thromboembolism (doubled) (CHADS2) inclusion criteria for the study (CHADS2 score of 3 or higher, or a CHADS2 score of 2 along with chronic obstructive pulmonary disease, sleep apnea, renal impairment, or coronary artery disease)	AF Predictors Analysis Cohort: No AF Episodes n=14 Actions at Visits Subjects successfully implanted with a Reveal Implantable Cardiac Monitor (ICM), and who (1) have post-implant ICM device data to evaluate, (2) were not on anti-arrhythmic medication at enrollment, (3) did not have AF prior to Reveal implant, and (4) did not experience an AF episode lasting at least 6 minutes during follow-up.	Third Visit With AF Detected n=6 Actions at Visits Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 3rd follow-up visit in which new AF episodes were diagnosed	Fourth Visit With AF Detected n=4 Actions at Visits Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 4th follow-up visit in which new AF episodes were diagnosed	Fifth Visit With AF Detected n=2 Actions at Visits Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 5th follow-up visit in which new AF episodes were diagnosed	Sixth Visit With AF Detected Enrolled subjects implanted with a Reveal Implantable Cardiac Monitor who: 1. Did not have diagnosed AF prior to implant, 2. met the CHADS2 score inclusion criterion (a CHADS2 score of at least 3 or a CHADS2 score of 2 with at least one of the following: coronary artery disease, sleep apnea, renal impairment, or chronic obstructive pulmonary disease), 3. was not taking an anti-arrhythmic drug at enrollment, and 4. Had a 6th follow-up visit in which new AF episodes were diagnosed
Actions Taken in Response to Awareness of AF Oral Anticoagulation Initiated	61 Actions at Visits	5 Actions at Visits	0 Actions at Visits	1 Actions at Visits	2 Actions at Visits	0 Actions at Visits
Actions Taken in Response to Awareness of AF Rhythm Control Medication Initiated	13 Actions at Visits	2 Actions at Visits	0 Actions at Visits	1 Actions at Visits	0 Actions at Visits	0 Actions at Visits
Actions Taken in Response to Awareness of AF Rate Control Medication Initiated	4 Actions at Visits	3 Actions at Visits	2 Actions at Visits	1 Actions at Visits	0 Actions at Visits	0 Actions at Visits
Actions Taken in Response to Awareness of AF Cardioversion	2 Actions at Visits	2 Actions at Visits	1 Actions at Visits	0 Actions at Visits	0 Actions at Visits	0 Actions at Visits
Actions Taken in Response to Awareness of AF Ablation	0 Actions at Visits	2 Actions at Visits	3 Actions at Visits	1 Actions at Visits	0 Actions at Visits	0 Actions at Visits
Actions Taken in Response to Awareness of AF Referral to Another Physician	5 Actions at Visits	0 Actions at Visits	0 Actions at Visits	0 Actions at Visits	0 Actions at Visits	0 Actions at Visits

Adverse Events

Reveal Implantable Cardiac Monitor Implant Attempted

Serious events: 153 serious events

Other events: 34 other events

Deaths: 13 deaths

No Reveal Implantable Cardiac Monitor Implant Attempt

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Reveal Implantable Cardiac Monitor Implant Attempted n=395 participants at risk Enrolled subjects who had a Reveal Implantable Cardiac Monitor implant attempt (i.e. underwent the procedure to have a Reveal device implanted)	No Reveal Implantable Cardiac Monitor Implant Attempt n=51 participants at risk Enrolled subjects who exited the study prior to undergoing a procedure to implant a Reveal Implantable Cardiac Monitor
Cardiac disorders Atrial fibrillation	8.6% 34/395 • Number of events 36 • Adverse events occurring from the time of enrollment (consent) until exit will be included. All subjects were to be followed a minimum of 18 months and a maximum of 30 months post-Reveal device implantation.	2.0% 1/51 • Number of events 1 • Adverse events occurring from the time of enrollment (consent) until exit will be included. All subjects were to be followed a minimum of 18 months and a maximum of 30 months post-Reveal device implantation.

Additional Information

Medtronic Cardiac Rhythm and Heart Failure clinical trial manager

Medtronic, Inc.

Phone: 763-505-6000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Generally, contracts allow investigators to publish study results per the protocol and publication plan. Investigators and participating institutions will provide any publication of study data generated by the Investigator and/or participating institution to Medtronic for review prior to submission to determine if confidential information ("CI") is included and to check for technical correctness. Medtronic may not censor/interfere with the publication beyond the extent necessary to protect CI.
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