Trial Outcomes & Findings for Adaptive Cardiac Resynchronization Therapy Study (NCT NCT00980057)

NCT ID: NCT00980057

Last Updated: 2018-10-16

Results Overview

Patients considered worsened if they died, were hospitalized with worsening heart failure (HF), crossed over to other arm, demonstrated worsening in New York Heart Association (NYHA) functional class, or reported moderately/markedly worse on 'patient global assessment' compared to before CRT implant. Patients are improved if they are not worsened and have an improved NYHA or reported moderately/markedly improved on the 'patient global assessment' compared to before CRT implant Global assessment question for the patient: Specifically in reference to your heart failure symptoms, how do you feel today as compared to how you felt before your CRT system was implanted? O Markedly improved O Moderately improved O Mildly improved O No change O Slightly worse O Moderately worse O Markedly worse

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 522 participants
• Primary outcome timeframe: randomization to six month visit
• Results posted on: 2018-10-16

Participant Flow

Total number of: * 522 pts enrolled, 1 exit * 521 pts with baseline information, 16 exits * 505 pts of which 14 unsuccessful implants and 491 successful implants, 12 exits and 1 death * 478 randomized (318 to aCRT, 160 to control)

Participant milestones

Measure	Adaptive CRT (aCRT) Pacing Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Overall Study STARTED	318	160
Overall Study COMPLETED	299	155
Overall Study NOT COMPLETED	19	5

Reasons for withdrawal

Measure	Adaptive CRT (aCRT) Pacing Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Overall Study Death	13	3
Overall Study Adverse Event	0	1
Overall Study Physician Decision	4	0
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Adaptive Cardiac Resynchronization Therapy Study

Baseline characteristics by cohort

Measure	Adaptive CRT (aCRT) Pacing n=318 Participants Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing n=160 Participants Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)	Total n=478 Participants Total of all reporting groups
Age, Continuous	65.4 years STANDARD_DEVIATION 11.2 • n=5 Participants	66.2 years STANDARD_DEVIATION 9.7 • n=7 Participants	65.7 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	51 Participants n=7 Participants	148 Participants n=5 Participants
Sex: Female, Male Male	221 Participants n=5 Participants	109 Participants n=7 Participants	330 Participants n=5 Participants
Race/Ethnicity, Customized Asian	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	29 Participants n=5 Participants	6 Participants n=7 Participants	35 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	13 Participants n=5 Participants	5 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	257 Participants n=5 Participants	139 Participants n=7 Participants	396 Participants n=5 Participants
Race/Ethnicity, Customized Two or more races	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Other race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Not available	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Russia	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Hong Kong	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United States	176 participants n=5 Participants	87 participants n=7 Participants	263 participants n=5 Participants
Region of Enrollment Japan	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Spain	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Saudi Arabia	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Canada	17 participants n=5 Participants	8 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Austria	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Netherlands	11 participants n=5 Participants	5 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Sweden	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Belgium	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Norway	7 participants n=5 Participants	3 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Denmark	11 participants n=5 Participants	7 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Italy	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Australia	18 participants n=5 Participants	12 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment Serbia	23 participants n=5 Participants	10 participants n=7 Participants	33 participants n=5 Participants
Region of Enrollment Germany	31 participants n=5 Participants	14 participants n=7 Participants	45 participants n=5 Participants

PRIMARY outcome

Timeframe: randomization to six month visit

Patients considered worsened if they died, were hospitalized with worsening heart failure (HF), crossed over to other arm, demonstrated worsening in New York Heart Association (NYHA) functional class, or reported moderately/markedly worse on 'patient global assessment' compared to before CRT implant. Patients are improved if they are not worsened and have an improved NYHA or reported moderately/markedly improved on the 'patient global assessment' compared to before CRT implant

Global assessment question for the patient: Specifically in reference to your heart failure symptoms, how do you feel today as compared to how you felt before your CRT system was implanted? O Markedly improved O Moderately improved O Mildly improved O No change O Slightly worse O Moderately worse O Markedly worse

Outcome measures

Measure	Adaptive CRT (aCRT) Pacing n=318 Participants Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing n=160 Participants Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Percentage of Patients With Improved Heart Failure Outcomes Clinical Composite Score	234 Participants	114 Participants

PRIMARY outcome

Timeframe: randomization visit and six month visit

Population: Concordance correlations have been calculated between AoVTI at Adaptive CRT AV and VV settings vs. echo-optimized AV and VV settings at randomization and 6 M. Paired AoVTI measurements were used for concordance correlation analysis, where each subject served as his/her own control. AoVTI was not obtained at both settings for 79 patients.

Correlation between aortic velocity time integral (AoVTI) at Adaptive CRT and echo-optimized device settings. AoVTI is an echocardiographic representative of stroke volume and cardiac performance.

Outcome measures

Measure	Adaptive CRT (aCRT) Pacing n=399 Participants Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Correlation Between Aortic Velocity Time Integral (AoVTI) at Adaptive CRT and Echo-optimized Device Settings	0.93 Concordance correlation coefficient Interval 0.91 to 0.94	—

PRIMARY outcome

Timeframe: randomization to 6 months post randomization

Population: 17 participants did not have data available for analysis of this endpoint.

For each subject, the Adaptive CRT-determined AV and VV delay settings from randomization up to 183-days post-randomization were evaluated to identify any period of 28-days with a wide delay range (>60 ms)

Outcome measures

Measure	Adaptive CRT (aCRT) Pacing n=301 Participants Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Percentage of Patients With a Safety Event (Inappropriate AV or VV Delay Settings Related to the aCRT Feature)	0 Participants	—

SECONDARY outcome

Timeframe: implant to six months post randomization

The percentage of time the right ventricle is paced by the device

Outcome measures

Measure	Adaptive CRT (aCRT) Pacing n=314 Participants Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing n=160 Participants Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Right Ventricular Pacing Percentage	51.3 percentage of right ventricle pacing Standard Deviation 37.9	95.1 percentage of right ventricle pacing Standard Deviation 10.5

SECONDARY outcome

Timeframe: baseline to six month visit

Change in left ventricular end systolic volume index (LVESVi).

Outcome measures

Measure	Adaptive CRT (aCRT) Pacing n=250 Participants Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing n=123 Participants Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Change in Left Ventricular End Systolic Volume Index (LVESVi)	-8.3 milliliters per meter squared Standard Deviation 23.3	-10.5 milliliters per meter squared Standard Deviation 24.2

SECONDARY outcome

Timeframe: baseline to six month visit

Outcome measures

Measure	Adaptive CRT (aCRT) Pacing n=250 Participants Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing n=123 Participants Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Change in Left Ventricular Ejection Fraction (LVEF)	3.9 percent Standard Deviation 10.0	2.9 percent Standard Deviation 9.8

SECONDARY outcome

Timeframe: baseline to six month visit

The New York Heart Association (NYHA) Functional Classification places patients in one of four categories based on how much they are limited during physical activity.

Class - Patient Symptoms I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath).

II- Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath).

III- Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.

IV- Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.

Outcome measures

Measure	Adaptive CRT (aCRT) Pacing n=296 Participants Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing n=153 Participants Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Change in New York Heart Association (NYHA) Classification	-1.0 NYHA class Standard Deviation 0.8	-0.8 NYHA class Standard Deviation 0.8

SECONDARY outcome

Timeframe: baseline to six month visit

Outcome measures

Measure	Adaptive CRT (aCRT) Pacing n=284 Participants Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing n=142 Participants Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Change in Distance Walked During the Six Minute Hall Walk	42.4 meters Standard Deviation 103.3	29.0 meters Standard Deviation 123.0

SECONDARY outcome

Timeframe: baseline to six month visit

The MLWHF is a 21 question survey. Scores range from 0-105, with lower scores indicating better health.

Outcome measures

Measure	Adaptive CRT (aCRT) Pacing n=261 Participants Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing n=135 Participants Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Change in Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire (MLWHF)	-19.3 units on a scale Standard Deviation 20.7	-17.6 units on a scale Standard Deviation 23.8

Adverse Events

Adaptive CRT (aCRT) Pacing

Serious events: 158 serious events

Other events: 50 other events

Deaths: 35 deaths

Standard Biventricular Pacing

Serious events: 86 serious events

Other events: 34 other events

Deaths: 19 deaths

Serious adverse events

Measure	Adaptive CRT (aCRT) Pacing n=318 participants at risk Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing n=160 participants at risk Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Blood and lymphatic system disorders Anaemia	1.3% 4/318 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	3.8% 6/160 • Number of events 6 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Blood and lymphatic system disorders Iron deficiency anaemia	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Blood and lymphatic system disorders Splenic infarction	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Acute coronary syndrome	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Acute myocardial infarction	1.3% 4/318 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Angina pectoris	0.94% 3/318 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Angina unstable	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Aortic valve stenosis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Arrhythmia supraventricular	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Atrial fibrillation	1.3% 4/318 • Number of events 5 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	3.1% 5/160 • Number of events 8 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Atrial flutter	1.3% 4/318 • Number of events 5 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Cardiac arrest	1.3% 4/318 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Cardiac failure	19.8% 63/318 • Number of events 112 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	21.9% 35/160 • Number of events 58 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Cardiac failure chronic	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Cardiac tamponade	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Cardiogenic shock	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Coronary artery disease	2.2% 7/318 • Number of events 7 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Heart valve incompetence	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Intracardiac thrombus	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.9% 3/160 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Mitral valve incompetence	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Myocardial infarction	0.63% 2/318 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Pericardial effusion	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Pulseless electrical activity	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Sinus tachycardia	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Supraventricular tachyarrhythmia	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Supraventricular tachycardia	0.94% 3/318 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Tachycardia	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Tricuspid valve disease	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Tricuspid valve incompetence	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Ventricular arrhythmia	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Ventricular fibrillation	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Ventricular tachyarrhythmia	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Ventricular tachycardia	2.5% 8/318 • Number of events 8 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	2.5% 4/160 • Number of events 6 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Congenital, familial and genetic disorders Atrial septal defect	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Ear and labyrinth disorders Vertigo	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Ear and labyrinth disorders Vertigo positional	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Eye disorders Cataract	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Ascites	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Colitis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Colonic polyp	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Constipation	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Diarrhoea	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Diverticular perforation	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Dysphagia	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Enterocutaneous fistula	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Food poisoning	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Gastric haemorrhage	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Gastritis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.3% 4/318 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	2.5% 4/160 • Number of events 5 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Haematochezia	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Inguinal hernia	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Intestinal ischaemia	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Intestinal obstruction	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Pancreatitis acute	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Peptic ulcer	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Peritoneal haemorrhage	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Rectal haemorrhage	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Gastrointestinal disorders Vomiting	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Asthenia	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Chest discomfort	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Chest pain	1.9% 6/318 • Number of events 6 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	2.5% 4/160 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Device capturing issue	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Device connection issue	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Device dislocation	3.5% 11/318 • Number of events 11 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	4.4% 7/160 • Number of events 10 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Device electrical impedance issue	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Device lead damage	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Device misuse	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Device pacing issue	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Device psychogenic complication	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Device stimulation issue	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Hernia	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Implant site haematoma	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Implant site pain	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Multi-organ failure	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Non-cardiac chest pain	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Polyp	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Sudden cardiac death	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Undersensing	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Hepatobiliary disorders Cholecystitis	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Hepatobiliary disorders Cholecystitis acute	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Immune system disorders Hypersensitivity	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Anal abscess	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Bacterial infection	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Bronchitis	1.3% 4/318 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Bronchopneumonia	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Campylobacter gastroenteritis	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Cellulitis	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.9% 3/160 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Clostridium difficile colitis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Device related infection	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Empyema	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Gastroenteritis	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Gastroenteritis viral	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Implant site infection	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	2.5% 4/160 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Infection	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Influenza	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Liver abscess	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Lower respiratory tract infection	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Parotitis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Pelvic abscess	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Pneumonia	5.0% 16/318 • Number of events 19 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	5.6% 9/160 • Number of events 12 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Postoperative wound infection	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Respiratory tract infection	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Sepsis	2.2% 7/318 • Number of events 9 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Septic shock	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Staphylococcal infection	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Upper respiratory tract infection	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Urinary tract infection	1.3% 4/318 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	2.5% 4/160 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Urosepsis	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Infections and infestations Wound infection pseudomonas	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Injury, poisoning and procedural complications Arteriovenous fistula occlusion	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Injury, poisoning and procedural complications Fall	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Injury, poisoning and procedural complications Fracture	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Injury, poisoning and procedural complications Head injury	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Injury, poisoning and procedural complications Hip fracture	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Injury, poisoning and procedural complications Pocket erosion	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Injury, poisoning and procedural complications Post-traumatic neck syndrome	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Investigations Blood bilirubin abnormal	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Investigations Clostridium test positive	0.31% 1/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Metabolism and nutrition disorders Dehydration	1.3% 4/318 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Metabolism and nutrition disorders Diabetes mellitus	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Metabolism and nutrition disorders Hyperglycaemia	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.9% 3/160 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Metabolism and nutrition disorders Hyperkalaemia	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.9% 3/160 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.9% 3/160 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Musculoskeletal and connective tissue disorders Arthralgia	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Musculoskeletal and connective tissue disorders Flank pain	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Musculoskeletal and connective tissue disorders Neck pain	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.31% 1/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Musculoskeletal and connective tissue disorders Pain in jaw	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to gastrointestinal tract	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Carotid artery stenosis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Cerebellar infarction	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Cerebral infarction	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Cerebrovascular accident	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Cervical root pain	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Dementia	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Encephalopathy	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Haemorrhage intracranial	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Headache	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Nerve compression	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Presyncope	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Subarachnoid haemorrhage	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Syncope	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Nervous system disorders Transient ischaemic attack	0.94% 3/318 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Renal and urinary disorders Obstructive uropathy	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Renal and urinary disorders Renal artery stenosis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Renal and urinary disorders Renal failure	1.9% 6/318 • Number of events 7 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Renal and urinary disorders Renal failure acute	2.5% 8/318 • Number of events 9 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	3.8% 6/160 • Number of events 6 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Renal and urinary disorders Renal impairment	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Renal and urinary disorders Urinary retention	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Reproductive system and breast disorders Rectocele	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.31% 1/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.6% 5/318 • Number of events 7 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	3.8% 6/160 • Number of events 11 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Skin and subcutaneous tissue disorders Angioedema	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Surgical and medical procedures Bladder neoplasm surgery	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Surgical and medical procedures Heart transplant	0.94% 3/318 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Aortic aneurysm	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Aortic stenosis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Arterial occlusive disease	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Arterial stenosis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Deep vein thrombosis	0.94% 3/318 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Embolism	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Haematoma	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Hypertension	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Hypertensive crisis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Hypertensive emergency	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Hypotension	0.94% 3/318 • Number of events 3 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	1.2% 2/160 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Intermittent claudication	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Orthostatic hypotension	1.3% 4/318 • Number of events 4 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Peripheral vascular disorder	0.63% 2/318 • Number of events 2 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Thrombophlebitis superficial	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Thrombosis	0.31% 1/318 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.00% 0/160 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Vascular disorders Vena cava thrombosis	0.00% 0/318 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	0.62% 1/160 • Number of events 1 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.

Other adverse events

Measure	Adaptive CRT (aCRT) Pacing n=318 participants at risk Cardiac resynchronization therapy (CRT) with adaptive pacing Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D) Adaptive CRT (aCRT) Pacing: Adaptive CRT pacing software adjusts how the device paces the heart based on the patient's current heart status	Standard Biventricular Pacing n=160 participants at risk Cardiac resynchronization therapy (CRT) with biventricular pacing only (without adaptive pacing) Cardiac Resynchronization Therapy-Defibrillator (CRT-D): Market approved Medtronic Vision 3D™ CRT-D implantable device (Consulta® CRT-D, Maximo II® CRT-D, or Concerto II® CRT-D)
Cardiac disorders Atrial fibrillation	3.1% 10/318 • Number of events 10 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	8.8% 14/160 • Number of events 15 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
Cardiac disorders Cardiac failure	8.8% 28/318 • Number of events 33 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	8.8% 14/160 • Number of events 15 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.
General disorders Device stimulation issue	4.4% 14/318 • Number of events 17 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.	6.2% 10/160 • Number of events 14 • From randomization to the end of the study, which was 31.3 months for the longest-randomized patient. The average follow-up time was 20.2 months.

Additional Information

Adaptive CRT Clinical Research Specialist

Medtronic, Inc

Phone: 800-328-2518

Email: medtronicCRMtrials@medtronic.com

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 PI 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.
• Publication restrictions are in place

Restriction type: OTHER