Trial Outcomes & Findings for The Influence of Heart Rate Limitation on Exercise Tolerance in Pacemaker Patients. (NCT NCT02247245)

Results Overview

Cardiopulmonary exercise testing performance - measuring peak oxygen uptake during a treadmill CPEX test. Subjects were exercised using the Bruce protocol, modified by the addition of a "stage 0" at onset consisting of 3 min of exercise at 1.61 km·h-1 (1 mile·h-1) with a 5% gradient. Expired air was collected and metabolic gas exchange analysis performed in order to measure the maximal oxygen consumption (peak VO2) (Sensormedics, Yorba Linda, California). The CPX equipment was recalibrated before every exercise test. All test subjects were encouraged to exercise to exhaustion before starting the test, and no further motivation or instructions were given.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

40 participants

Primary outcome timeframe

Each test lasts up to 20 minutes

Results posted on

2020-01-02

Participant Flow

The predicted group size to demonstrate a clinically important change was revised after post hoc analysis of pilot data demonstrating higher pVO2 values for both SR and AF than expected (minimum requirements:12 subjects in AF group, 20 in SR group). To allow for dropouts, recruitment targets were altered 14 with AF and 26 with SR (total 40).

Participant milestones

Participant milestones
Measure	Placebo First Subjects are given a placebo capsule (double-blinded) to take 90 minutes prior to the cardiopulmonary exercise test. Placebo: Placebo n=13 Placebo first, washout 1 week, then Ivabradine 7.5mg	Ivabradine First Subjects are given an ivabradine capsule (double-blinded) to take 90 minutes prior to the cardiopulmonary exercise test. Ivabradine: Ivabradine 7.5mg Ivabradine 7.5mg first, washout 1 week, then placebo	Atrial Fibrillation (Low Rate) Atrial fibrillation with pacemaker base rate alteration: Subjects are (double blind) randomised to either a low base pacing rate (30) or a standard base rate (60), with rate adaptive algortithms switched on.	Atrial Fibrillation (Standard Rate) Atrial fibrillation with pacemaker base rate alteration: Subjects are (double blind) randomised to either a low base pacing rate (30) or a standard base rate (60), with rate adaptive algortithms switched on.
Overall Study STARTED	13	13	7	7
Overall Study COMPLETED	13	13	7	7
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo First n=13 Participants Subjects are given a placebo capsule (double-blinded) to take 90 minutes prior to the cardiopulmonary exercise test. Placebo: Placebo	Ivabradine First n=13 Participants Subjects are given an ivabradine capsule (double-blinded) to take 90 minutes prior to the cardiopulmonary exercise test. Ivabradine: Ivabradine 7.5mg	Atrial Fibrillation (Low Rate) n=7 Participants Atrial fibrillation with pacemaker base rate alteration: Subjects are (double blind) randomised to either a low base pacing rate (30) or a standard base rate (60), with rate adaptive algortithms switched on. This group - low base pacing rate (30)	Atrial Fibrilaltion (Standard Rate) n=7 Participants Atrial fibrillation with pacemaker base rate alteration: Subjects are (double blind) randomised to either a low base pacing rate (30) or a standard base rate (60), with rate adaptive algortithms switched on. This group - standard base pacing rate (60)	Total n=40 Participants Total of all reporting groups
Age, Continuous	74 years STANDARD_DEVIATION 9 • n=13 Participants	74 years STANDARD_DEVIATION 9 • n=13 Participants	76 years STANDARD_DEVIATION 10 • n=7 Participants	76 years STANDARD_DEVIATION 10 • n=7 Participants	74 years STANDARD_DEVIATION 9 • n=40 Participants
Sex: Female, Male Female	3 Participants n=13 Participants	3 Participants n=13 Participants	2 Participants n=7 Participants	2 Participants n=7 Participants	10 Participants n=40 Participants
Sex: Female, Male Male	10 Participants n=13 Participants	10 Participants n=13 Participants	5 Participants n=7 Participants	5 Participants n=7 Participants	30 Participants n=40 Participants
Race and Ethnicity Not Collected	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United Kingdom	13 participants n=13 Participants	13 participants n=13 Participants	7 participants n=7 Participants	7 participants n=7 Participants	40 participants n=40 Participants
New York Heart Association classification	2 units on a scale n=13 Participants	2 units on a scale n=13 Participants	2 units on a scale n=7 Participants	2 units on a scale n=7 Participants	2 units on a scale n=40 Participants

PRIMARY outcome

Timeframe: Each test lasts up to 20 minutes

Cardiopulmonary exercise testing performance - measuring peak oxygen uptake during a treadmill CPEX test. Subjects were exercised using the Bruce protocol, modified by the addition of a "stage 0" at onset consisting of 3 min of exercise at 1.61 km·h-1 (1 mile·h-1) with a 5% gradient. Expired air was collected and metabolic gas exchange analysis performed in order to measure the maximal oxygen consumption (peak VO2) (Sensormedics, Yorba Linda, California). The CPX equipment was recalibrated before every exercise test. All test subjects were encouraged to exercise to exhaustion before starting the test, and no further motivation or instructions were given.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Subjects are given a placebo capsule (double-blinded) to take 90 minutes prior to the cardiopulmonary exercise test. Placebo: Placebo	Ivabradine n=13 Participants Subjects are given an ivabradine capsule (double-blinded) to take 90 minutes prior to the cardiopulmonary exercise test. Ivabradine: Ivabradine 7.5mg	Atrial Fibrillation: Low Base Rate (+no Rate Adaptive Pacing) n=7 Participants Subjects are (double blind) randomised to either a low base pacing rate (30) or a standard base rate (60), with rate adaptive algorithms switched on. Atrial fibrillation: Pacemaker base rate alteration	Atrial Fibrn: Standard Base Rate (+Rate Adaptive Pacing) n=7 Participants Subjects are (double blind) randomised to either a low base pacing rate (30) or a standard base rate (60), with rate adaptive algortithms switched on. Atrial fibrillation: Pacemaker base rate alteration
Maximal Oxygen Consumption (Peak VO2)	16 ml/kg/min Standard Error 3	17 ml/kg/min Standard Error 3	15.3 ml/kg/min Standard Error 1.9	14.2 ml/kg/min Standard Error 2.1

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Ivabradine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Atrial Fibrillation (Low Rate)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Atrial Fibrilaltion (Standard Rate)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr Haqeel Jamil

University of Leeds

Phone: 0113 343 3241

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place