Clinical trial NCT04600713: Physiotherapist-led Exercise Within Cardiac Rehabilitation and Paroxysmal Atrial Fibrillation and COVID-19.
Official title: Physiotherapist Led Exercise Within Cardiac Rehabilitation and Inspiratory Muscle Training and Patients With Paroxysmal Atrial Fibrillation - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Atrial Fibrillation Paroxysmal
Keywords: Health Related Quality of Life
Exercise
Physiotherapy
Physical Activity
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
First posted: 2020-10-23
Enrollment: 0
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled multicenter study
Primary purpose: TREATMENT

Brief summary: Paroxysmal atrial fibrillation (AF) induce, in the affected patient, a prominent negative effect on health-related quality of life (HR-QoL) and physical fitness. The health care utilisation is high and the patient does never know when the next attack of atrial fibrillation occurs. Therefore, is physical exertion often avoided due to fear of new attacks. Further, are shortness of breath and fatigue often present despite of prescribed modern drugs. Paroxysmal AF per se enhance markedly the risk to develop stroke and heart failure, which both are syndromes that cause further negative effect on the patient´s HR-QoL and physical fitness. Altogether, cause the symptoms in paroxysmal AF a vicious spiral where both VO2max and muscle function deteriorate. The problems with shortness of breath might be due to dysfunction in respiratory muscles. Physiotherapy led exercise within cardiac rehabilitation (PT-X) in combination with inspiratory muscle training (IMT) has shown positive effects in patients with permanent atrial fibrillation. However, to our knowledge, not yet investigated in patients with paroxysmal AF.

Aim: Primary to investigate, in a multicentre randomised controlled trial, if PT-X in combination with IMT can impact HR-QoL in patients with paroxysmal AF. Secondary to investigate the effect of PT-X in combination with IMT regarding symptoms, physical fitness, physical activity and the number of atrial fibrillation attacks and health care costs compared to the control group, asked to live their usual life, during the study period.

Expected outcome: PTX in combination with IMT can improve HR-QoL, respiratory muscle function, level of symptoms, physical fitness and physical activity in patients with paroxysmal AF. In addition, a reduced number of atrial fibrillation attacks could decrease the direct cost of health care.

Detailed description: Introduction Paroxysmal atrial fibrillation (AF) induce, in the affected patient an increased risk of stroke and heart failure. The corner stone in the medical treatment for AF is anticoagulants and heartrate regulators which affect the physical fitness. Other interventions available for rhythm regulation such as antiarrhythmic drugs, cardioversion and catheter ablation are alternatives aimed to be relief the symptoms of AF and increase the health-related quality of life (HR-QoL). Despite this advanced pharmacologic- and electrotherapy studies evaluating Patient Related Outcomes measures (PROMs) have shown that the symptoms persist and the HR-QoL is still reduced after treatment. Furthermore, Gleason et al, have recently shown that women have a comparatively higher frequency of symptoms, anxiety and depression despite type of intervention. The majority \> 90 %, of the patients with paroxysmal AF have symptoms such as palpitations, chest pain, reduced physical fitness and breathlessness. The unpredictability regarding the source of an AF attack, duration and frequencies causes the patient suffering, high healthcare utilization and increased sick leave, this result in high expenditures for AF related causes both for the patient and society. To avoid physical activity and exercise due to fear of an AF attack is not unusual, which may further lead to a reduced physical fitness i.e maximal oxygen capacity (VO2max) and an increased risk of stroke and mortality. This may lead to an evil circle with additional reduced physical fitness, possibly an increase in symptoms and a more reduced HR-QoL. The underlying causes of reduced physical fitness and breathlessness associated with AF is probably multifactorial. One reason could be skeletal muscle abnormities as in heart failure, which often coexists with AF. An increased mortality in the novel Coronavirus (COVID-19) caused by the SARS-CoV-2 is seen in individuals with older age, cardiovascular disease and in men, and the most usual complication is arrythmia such as AF. COVID-19 is a disease that affect the persons lungs and it is not uncommon with pulmonary complications. This can lead to an increased demand for exercise-based rehabilitation in patients with AF and reduced inspiratory muscle strength. One study has shown that a reduced respiratory muscle function can positively be affected with inspiratory muscle training in patients with permanent AF. Furthermore, a Cochrane report have shown that exercise can improve physical fitness in patients with AF, however, no effect was seen in HR-QoL. However, patients with paroxysmal AF, were underrepresented and additional studies concerning patients with paroxysmal AF are requested. Whether physiotherapist-led exercise-based cardiac rehabilitation (PT-X) and inspiratory muscle training (IMT) can improve physical fitness and positively affect symptoms and consequently improve HR-QoL is to our knowledge not studied.

Aim Primary to investigate, in a multicentre randomised controlled trial, if PT-X in combination with IMT can impact HR-QoL in patients with paroxysmal AF. Secondary to investigate the effect of PT-X in combination with IMT regarding symptoms, physical fitness, physical activity and the number of atrial fibrillation attacks and health care costs compared to the control group, asked to live their usual life, during the study period. Further to investigate the prevalence of antibodies for SARS-CoV-2, and the patient's own experience of how COVID-19 has affected their incidence and symptoms of paroxysmal AF.

Question formulations:

Primary question How will participation in PT-X and IMT impact the short form SF-36 general health score compared to the control group that is allowed to continue with their usual life? Secondary questions How will participation in PT-X and IMT impact the exercise capacity compared to the control group that is allowed to continue with their usual life? How will participation in PT-X and IMT affect symptoms of AF and fatigue compared to the control group that is allowed to continue with their usual life? How will participation in PT-X and IMT affect the muscle function compared to the control group that is allowed to continue with their usual life? How will participation in PT-X and IMT affect the frequency, duration and number of AF attacks compared to the control group that is allowed to continue with their usual life? How is the incidence of depression among the participants in the study, and is it possible to impact the prevalence of AF with participation in PT-X and IMT compared to the control group that is allowed to continue with their usual life? How has the COVID-19 affected the patient's own experience of number of attacks, symptoms and duration of AF? How is the prevalence of antibodies for SARs-CoV-2 among the participants in the present study? Method Study design A multi-centre randomised controlled trial Patients A total of 180 patients with paroxysmal AF, age 40 - 85 years, visiting the cardiology clinic at SV Hospital group Alingsås Hospital, Sahlgrenska University Hospital and primary care will be asked to participate in the study. Advertising in the daily press will be made for participants with paroxysmal AF. The patients will be informed both verbal and in written information, and a written informed consent will be obtained.

Statistics and power calculation The patients will be randomised stratified after sex, age and exercise capacity measured by the symptom-limited ergometer cycle test. Ratio and interval data will be presented as mean (± 1 SD), ordinal data will be presented as median (range) and nominal data in absolute and relative numbers. Depending on if the data are normal distributed or not the Student T-Test or the Mann-Whitney U- test will be used for evaluation of differences between the groups. Chi2 test will be used for evaluation of differences between the nominal data.

The sample size was calculated using a power (β) of 80% and a significance level of (α) 5%. Based on the assumption of a mean (SD) significant (p=0.05) difference in the PT-X group compared to the control group regarding improvement of SF-36 General Health score of 7.5 ± 15 points a total of 76 patients are needed in each group. Based on the assumption of a calculated withdraw of approximately 20% a total of 180 participants are needed to be included in this study.

Eligibility criteria: Inclusion Criteria:

* Paroxysmal atrial fibrillation verified with electrocardiogram (ECG)
* Left ventricular ejection fraction (EF) ≥ 45% verified by Echocardiography

Exclusion Criteria:

* Ongoing participation in regular aerobic and muscular endurance exercises more than 1 time per week.
* Participation in a weight reduction program.
* Smoking cessation program
* Treatment for sleep apnoea.
* Coronary event or angina pectoris within 3 months prior to inclusion
* stroke with residual symptoms
* presence of pacemaker
* No significant valvular lesions verified by Echocardiography.

Primary outcomes:
measure: Health-related quality of life
timeFrame: Change from baseline at 12 weeks
Secondary outcomes:
measure: N-terminal pro-B type natriuretic peptide (NT-proBNP)
timeFrame: At baseline
measure: Antibodies for SARS-CoV-2
timeFrame: At baseline
measure: Inspiratory and expiratory muscle strength
timeFrame: Change from baseline at 12 weeks
measure: Exercise capacity
timeFrame: Change from baseline at 12 weeks
measure: Muscle function
timeFrame: Change from baseline at 12 weeks
measure: Physical activity
timeFrame: Change from baseline at 12 weeks
measure: Self reported physical activity
timeFrame: Change from baseline at 12 weeks
measure: Self-reported anxiently and depression
timeFrame: Change from baseline at 12 weeks
measure: Handheld ECG heart rhythm
timeFrame: Through the study completion, an avarage of 12 weeks
measure: Direct hospital costs related to AF
timeFrame: Through the study completion, an avarage of 12 weeks
Other outcomes:
measure: Ejection fraction
timeFrame: At baseline
measure: Left ventricular function
timeFrame: At baseline
measure: Diastolic function
timeFrame: At baseline
measure: Valvular screening
timeFrame: At baseline
Locations:
Study officials:
affiliation: SV Hospital Group, Alingsås hospital Sweden
name: Maria Borland, PhD RPT
role: PRINCIPAL_INVESTIGATOR
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