The Norwegian Exercise in Atrial Fibrillation Trial

Atrial Fibrillation Clinical Trial

— NEXAF  

Official title:

The Norwegian Exercise in Atrial Fibrillation Trial - A Pragmatic, Open-label, Multicenter Randomized Controlled Trial Comparing an eHealth-based Exercise Intervention With Usual Care After 12 Months Follow-up

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05164718
• Other study ID #: 213848
• Secondary ID: 9053830031557822
• Status: Recruiting
• Phase: N/A
• Start date: February 4, 2022
• Est. completion date: July 2024

Study information

• Verified date: March 2023
• Source: Norwegian University of Science and Technology
• Contact: Bjarne M Nes, phd
• Phone: +47 72828139
• Email: bjarne.nes[@]ntnu.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Atrial fibrillation (AF) patients suffer a high symptom burden and reduced quality of life (QoL), high hospitalization rates and few effective treatment options. They have a high burden of cardiovascular risk factors and events. Lifestyle changes and exercise is a cornerstone of management in most chronic cardiac conditions and holds promise in AF, but the evidence is sparse and specific guidelines for exercise do not exist for AF patients. NEXAF is a large-scale multicenter randomized trial to determine the feasibility and effects of exercise on patient-reported and clinical outcomes. All patients will undergo continuous rhythm monitoring, enabling assessment of duration, frequency and total time of AF episodes. The overall aim of the study is to provide documentation for clinical exercise recommendations in AF. The objectives are to examine the effects of a 1-year exercise intervention in AF patients on (i) QoL and symptom burden, (ii) time-in-AF, and peak oxygen uptake, cardiac structure and function, cardiovascular risk factors and use of healthcare resources.

Description:

A pre-planned substudy will examine the immediate (24-h to 7 days) effects of vigorous exercise on AF-burden in a subgroup of participants from each arm. Two main outcomes are prespecified: (i) mean time-in-AF measured by an insertable cardiac monitor (ICM) 24 hours after maximal exercise testing at baseline and follow-up compared to mean of the last week before exercise test. (ii) Normal cardiac biomarker response for Troponin and NT-proBNP to acute exercise (0h, 3h, 24h post exercise). Secondary outcomes are mean time-in-AF the consecutive week and post-exercise heart rate variability and number of atrial and ventricular extra systoles at the same time points. Further, changes in post-exercise responses after the intervention (12 months) and the effect on clinical outcomes will be examined.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• Signed informed consent

• Diagnosed with paroxysmal or persistent AF in hospital registries

• In sinus rhythm at baseline screening

• Report <75 minutes per week of vigorous and/or <150 minutes of moderate intensity exercise the last three months

• Use a smartphone

Exclusion Criteria:

• Permanent AF or persistent AF with at least one continuous episode lasting =3 months the last year

• AF as a complication of acute coronary syndromes, cardiothoracic surgery or infections

• Planned ablation procedure next 12 months or ablated last 12 months without known recurrence

• Unstable coronary heart disease

• De-compensated heart failure

• Left ventricular ejection fraction <40%

• At least moderate to severe mitral or aortic pathology, or aortic aneurysms clinically incompatible with safe exercise

• Moderate to severe chronic obstructive pulmonary disease (GOLD group C+D)

• Ongoing severe cancer or active cancer treatment

• Pacemaker or ICD

• Pregnancy

• Alcohol or drug abuse

• Cognitive or serious psychiatric disease that may impede protocol compliance

• Physical impairments or diseases hindering exercise or making exercise contraindicated

• Resident of nursing home or other institution

• Participation in conflicting research studies (i.e. lifestyle interventions)

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Behavioral:
• Supervised home-based exercise
150-300 minutes of moderate intensity activity (55-75% of maximum heart rate in sinus rhythm or RPE 12-13 on the Borg Scale) or 75-150 minutes of vigorous intensity activity (75-90% of maximum heart rate or 14-16 on the Borg Scale) per week, or an equivalent combination of both, according to current general recommendations, including also those with established CVD. To maximize the potential for improvements in cardiorespiratory fitness, we encourage that at least 40-60 minutes per week (i.e. 2 sessions á 20-30 minutes) should be of vigorous intensity.

Other:
• Usual care
Standard management according to usual practice at the respective participating centers, including medical therapy as per guidelines. Prior to randomization all will be provided an ICM (Confirm RX™). The UC group will receive information about general PA recommendations as per guidelines at study enrollment. No further supervision is given.

Locations

Country	Name	City	State
Norway	Vestre Viken HF	Drammen
Norway	University Hospital of North Norway	Tromsø
Norway	St Olavs Hospital	Trondheim

Sponsors (5)

Lead Sponsor	Collaborator
Norwegian University of Science and Technology	St. Olavs Hospital, UiT The Arctic University of Norway, University Hospital of North Norway, Vestre Viken Hospital Trust

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Other changes in cardiac structure and function	Echocardiographic indices of atrial and ventricular structure and function	12 months
Other	Change in blood pressure	Change in resting systolic, diastolic and mean arterial blood pressure (diastolic BP + 1/3 x pulse pressure) measured in mmHg at baseline and 12 months.	12 months
Other	Change in lipids	Change in HDL-, LDL-, total cholesterol and triglycerides measured in mmol/L at baseline and 12 months.	12 months
Other	Change in body weight	Change in body weight measured in kilograms in all participants at baseline and 12 months. Change in fat- and muscle mass in kilograms in a subgroup of participants at baseline and 12 months.	12 months
Other	Acute biomarker response to high-intensity exercise	Level of hs-troponins, NT-proBNP and inflammatory markers pre and post maximal exercise. Biomarker response as predictors of change in AF burden and cardiac remodelling and future events will be evaluated, as well as change in biomarker response post-intervention.	0, 3 and 24 hours, respectively, after maximal exercise test compared to resting values at baseline and 12 months follow-up
Other	Cognitive function parameters	Measured by a web-based test battery (Memoro)	12 months
Other	Usability	Measured by the 10-item system usability scale.	12 months
Other	Immediate effects of vigorous exercise on time-in-atrial fibrillation	Post-exercise time-in-atrial fibrillation (% of day) measured by implantable loop recorder, heart rate and variability and other rhythm parameters (i.e. ventricular and atrial extrasystoles) the following days after a maximal exercise test will be compared to baseline values the preceding days. Echocardiographic predictors of post-exercise AF episodes will be evaluated.	0-7 days (daily and cumulative) after maximal test pre- and post-intervention
Other	Perceived competence for exercise	Perceived competence will be measured using overall score (4-28, higher score indicates better competence) of the 4-item perceived competence scale (PCS) for regular exercise in both groups at 12 months.	12 months
Other	Self-efficacy for exercise	Self-efficacy will be measured using the overall score (9-90, higher score indicates better self-efficacy) of the 9-item Self-Efficacy for Exercise Scale (SEE-EX) in both groups at 12 months.	12 months
Primary	Change in health-related quality of life and symptoms	Overall score (0-100) of the 20-item Atrial Fibrillation Effect and Quality of Life (AFEQT) questionnaire. The subscale scores on symptoms, daily activities, and treatment concern, respectively, and the overall score at 6 months, will aid to interpretation as secondary endpoints. Two questions regarding satisfaction with health care providers and treatment are not included in the overall score and will not be collected.	12 months
Primary	Total time-in-AF(%)	Measured by implantable loop recorder over 12 months	12 months
Secondary	Frequency and duration of AF episodes	Number of recorded AF episodes during follow-up will be calculated from the continuous ILR measurement over the 12 months. We will analyze between group differences (exercise vs. conventional management) in number of continuous AF episodes =30s, =24h and =7 days, respectively, as well as differences in median episode duration.	12 months
Secondary	Frequency and severity of atrial fibrillation symptoms	Measured by the 16-item AF symptoms and severity checklist. Total score on frequency and severity, respectively, and a subscore of AF-specific symptoms will be analyzed.	6 and 12 months
Secondary	Change in peak oxygen uptake (VO2peak)	Measured by ergospirometry pre- and post-intervention	12 months
Secondary	Change in physical and mental dimensions of health	The 12 item RAND-12 questionnaire corresponding to eight principal physical and mental health domains. Summarized into two scores; "Physical Health Summary Measure (PCS-physical component score)" and "Mental Health Summary Measure (MCS-mental component score). The EQ-VAS score will ask the patients to simply rate their current health status on a 0-100 scale ranging from "the best health you can imagine" to "the worst health you can imagine".	6 months and 12 months
Secondary	Change in cardiovascular risk factors	Sum of z-scores of waist, blood pressure, HDL-cholesterol, triglycerides and glucose.	12 months
Secondary	Changes in atrial volume and dimensions	Echocardiographic indices of left atrial volume and left atrial to left ventricle volume ratio	12 months
Secondary	Incident cardiovascular events, cardioversions and total hospitalization	Information about hospitalizations and the discharge diagnoses will be collected by journal review	12 months
Secondary	Safety outcome parameters	Death or unplanned hospitalization summarized per treatment group.	12 months
Secondary	Physical activity level and adherence	Self-reported physical activity (PA) will be measured by questionnaire consisting of 3 items (frequency, duration and intensity of regular exercise) in both groups at baseline, 6- and 12 months. Responses of frequency (exercise sessions per week) will be combined with duration of exercise (minutes per session) to estimate weekly minutes of exercise. Minutes of exercise will then be combined with reported intensity (light, moderate, vigorous) to calculate exercise volume and evaluate adherence to the intervention (numbers above and below recommended volume). Objective PA from wearable device in intervention group will be evaluated by minutes per week at light, moderate and vigorous intensity (% of maximal heart rate) and Personal Activity Intelligence (PAI) score (0-100).	6 and 12 months.