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Trial registered on ANZCTR


Registration number
ACTRN12616001109493
Ethics application status
Approved
Date submitted
8/08/2016
Date registered
16/08/2016
Date last updated
9/02/2022
Date data sharing statement initially provided
14/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Integrated Care for Atrial Fibrillation Management: A Randomised Controlled Trial
Scientific title
Effectiveness of Integrated Care Management for Atrial Fibrillation on all-cause hospitalisation and mortality: A Randomised Controlled Trial
Secondary ID [1] 286863 0
Nil known
Universal Trial Number (UTN)
Trial acronym
iCARE-AF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 295262 0
Cardiovascular Risk Factors 299878 0
Condition category
Condition code
Diet and Nutrition 295508 295508 0 0
Obesity
Cardiovascular 295509 295509 0 0
Other cardiovascular diseases
Public Health 295510 295510 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multi-centre, prospective, randomised controlled study, evaluating the effect of integrated specialised clinics for patients with atrial fibrillation (AF). The specialised AF clinics include structured AF management and aggressive risk factor management.

The study population comprises adults with AF presenting to the emergency department or cardiology outpatient department. Participants in the active (intervention) group undergo protocolised clinical investigation, including an echocardiogram, 24-hour Holter monitoring or treadmill (to assess rate control), laboratory testing (thyroid function and cardiovascular profile) and ECG, before visiting the specialised AF outpatient clinic (iCARE-AF clinic). The treatment team includes e.g., cardiologists, electrophysiologists, general practitioners, specialist nurses, and pharmacists, providing integrated and comprehensive management. The specialist nurse is the case manager and care coordinator. The intervention period for each participant is two years from the date of enrolment.

Participants in the intervention group attend 3-monthly consultations (30-45 minutes) in the first year. During these consultations, the specialist nurse will record the participant’s medical history and screen for cardiovascular (CV) risk factors. The nurse provides structured education, tailored to the individual’s abilities and needs, incorporating the cardiac condition, possible complications, and diagnostic test results. This will support treatment options and risk factor management.

During the intervention, the care provider uses decision-support software for comprehensive AF and CV risk management. The software serves as an electronic checklist to prevent incomplete diagnostic and therapeutic guideline-adherent AF and CV risk management and can be used to support the participant’s educational goals. The software is designed as a tool to assist both care provider and study participant to provide tailored care and education, which requires participant input during consultations. This system helps to navigate and support decision-making for the treatment team throughout the integrated care process.

CV risk factor management will be performed using an approach that has been successfully used in a prior study from our group and was assessed and approved by the Royal Adelaide Hospital HREC. This includes the following elements:

WEIGHT LOSS management will be approached using structured, multidisciplinary, motivational, and goal-directed face-to-face visits every 3 months in the first year, and every 6 months thereafter for study participants with a BMI of equal to or greater than 27kg/m2. Nutritional behaviour reflection, barriers to goal achievement and nutritional decision coaching will be addressed in the 20-40-minute counselling sessions. Verbal and written tailored education materials will be provided. The participant will also be able to schedule additional intervention visits in the event of an impending relapse. If additional support is required, contact can be made via telephone, email or through the patient application.

Initial weight reduction will be attempted by a meal plan and behaviour modification program, with emphasis on education for permanent lifestyle changes and behaviour modification program. The initial goal will be to reduce body weight by 10% from baseline in those with a BMI of equal to or greater than 27kg/m2.

Lifestyle Journal - Participants in the intervention group will be instructed to maintain a self-monitoring lifestyle journal, covering dietary intake and exercise.

Exercise – Physical activity is initially prescribed at low intensity for 20 minutes thrice weekly, based on participant's choice. This will be increased to achieve 210 minutes of moderate-intensity physical activity each week. Type and duration of activity is logged into the lifestyle journal.

CARDIO-METABOLIC RISK ASSESSMENT AND MANAGEMENT - Coexistent CV risk factors as indicated below, will be identified through the participant’s historical medical records and fasting plasma testing. Following identification, optimal management according to current evidence-based practice guidelines will be addressed by the specialist nurse/cardiologist during the 30-45-minute consultations and participants will be referred to dedicated specialists (e.g., diabetes and sleep disordered breathing) if indicated.

HYPERTENSION – Participants will be asked to measure their blood pressure (BP) twice daily using a home-automated monitor. In addition, exercise stress testing will be performed to determine the presence of exercise-induced hypertension. Increase in blood pressure to over 200/100 with exercise will be considered further evidence to optimize control. Initial therapeutic advice will include dietary salt restriction and weight loss with increase in aerobic physical activity. Pharmacotherapy will be initiated using angiotensin-aldosterone axis active agents by preference, and other agents where necessary to achieve a target BP of <130/80mmHg at rest on at least 80% of random acquired blood pressure readings as listed above. Further, echocardiography will be used to monitor any objective evidence of end-organ injury (e.g., left ventricular hypertrophy). Changes in the dose and number of anti-hypertensive agents will be recorded at each intervention visit.

GLUCOSE TOLERANCE - If fasting glucose is between 5.5 and 7mmol/L, a 2-hour oral glucose tolerance test will be performed. Impaired glucose tolerance (IGT) will be initially managed with lifestyle measures such as diet and aerobic exercise. If participants are unable to maintain glycosylated haemoglobin values below 6.5% after three months, metformin will be started. Participants with poor glycaemic control (HbA1c>7%) will be referred to a diabetes clinic.

DISLIPIDAEMIA – Management of dyslipidaemia will be in accordance with the evidence-based practice guidelines. Initially lifestyle measures will be used. Statins will be initiated if participants are unable to achieve LDL-Cholesterol of less than 100mg/dL after 3 months.

SLEEP APNEA - All study participants will complete a screening questionnaire to assess potential sleep disordered breathing and will be referred to a dedicated sleep disorder unit for overnight polysomnography if indicated. Continuous positive airway pressure (CPAP) will be prescribed in the presence of a clinically compatible history of sleep apnoea and sleep study results (Respiratory Disturbance Index [RDI] and desaturation levels). Generally, continued lifestyle measures with periodic evaluation may be pursued if RDI is between 15-30, CPAP will be prescribed if RDI is greater than 30.

SMOKING - The “5A” (Ask, Assess, Advice, Assist and Arrange follow up) structured smoking cessation framework will be adapted. Smokers will be offered behavioural support and follow-up within the specialised clinic. Pharmacotherapy may be included.

ALCOHOL - Written and verbal counselling will be provided aiming to reduce alcohol intake to no more than 3 standard drinks per week, with regular supportive follow up for alcohol reduction or abstinence.
Intervention code [1] 292038 0
Treatment: Other
Intervention code [2] 292039 0
Lifestyle
Comparator / control treatment
Participants randomly allocated to Usual Care group will continue to receive care from their existing health care provider. Clinical investigation, treatment of AF, follow up, and risk factor management will be determined by the treating physician.
Control group
Active

Outcomes
Primary outcome [1] 295244 0
A composite of all-cause mortality and hospitalisation. Medical records and death reports will be screened to assess hospitalisation and mortality. These events will be adjudicated by an independent Endpoint Adjudication Committee.
Timepoint [1] 295244 0
Baseline, 3, 6, 9, 12, 18, 24 MONTHS
Secondary outcome [1] 315177 0
CARDIOVASCULAR HOSPITALISATION according to MACCE classification includes: admissions for arrhythmic events (AF, atrial arrhythmias, sustained ventricular tachycardia, cardiac arrest) confirmed on ECG; embolic complications (incl. ischemic stroke, Transient Ischemic Attack, peripheral, pulmonary or systemic embolism) confirmed by a neurologist based on computerized tomography or Magnetic Resonance Imaging; major bleeding (drop in Hemoglobin level by >2 g/L, or requiring blood transfusion); heart failure (independent of left ventricular ejection fraction, preferably confirmed by biomarker assessment using NT-pro-BNP); acute coronary syndrome (including STEMI/NSTEMI or unstable angina pectoris) documented on ECG as well as/or assessed in blood levels of key chemical markers
Timepoint [1] 315177 0
Baseline, 3, 6, 9, 12, 18, 24 MONTHS
Secondary outcome [2] 326637 0
CARDIOVASCULAR MORTALITY will be classified to cause including cardiac arrhythmic, cardiac non-arrhythmic and vascular non-cardiac. To assess this outcome, medical records and death certificates will be screened.
Timepoint [2] 326637 0
Baseline, 3, 6, 9, 12, 18, 24 MONTHS
Secondary outcome [3] 326638 0
AF SYMPTOM BURDEN AND SEVERITY will be assessed using the validated AF Severity Scale (Univeristy of Toronto, Canada)
Timepoint [3] 326638 0
Baseline, 3, 6, 9, 12, 18, 24 MONTHS
Secondary outcome [4] 326639 0
SLEEP APNOEA will be assessed using the Berlin questionnaire.
Timepoint [4] 326639 0
Baseline, 3, 6, 9, 12, 18, 24 MONTHS
Secondary outcome [5] 326640 0
CARDIOVASCULAR RISK FACTOR MANAGEMENT includes aggressive management of hypertension, diabetes, sleep apnea, cholesterol, and modifiable lifestyle factors such as weight, alcohol use and smoking.
This outcome will be assessed based on the recommendation of evidence-based guidelines for the Management of Absolute Cardiovascular Disease Risk.
Timepoint [5] 326640 0
Baseline, 3, 6, 9, 12, 18, 24 MONTHS
Secondary outcome [6] 326641 0
GUIDELINE-ADHERENT AF MANAGEMENT will be assessed based on the recommendations of evidence based AF management guidelines, including (i) ECG used to determine the diagnose AF; (ii) Echocardiogram within 1 month after first presentation to emergency or outpatient department, if not done within the previous 12 months; (iii) Laboratory testing of thyroid-stimulating hormone (TSH) and cardiovascular risk profile at emergency or outpatient department; (iv) Appropriate prescription of antithrombotic treatment (e.g. according to stroke and bleeding risk based on CHA2DS2-VASc and HAS-BLED score); (v) Inadvertent prescription of Vaughn-Williams class I drugs in patients with structural heart disease is avoided; (vi) Inadvertent application of rhythm control strategy to completely asymptomatic patients is avoided; (vii) Inadvertent prescription of anti-arrhythmic medication for rhythm control in patients with permanent AF is avoided.
Timepoint [6] 326641 0
Baseline, 3, 6, 9, 12, 18, 24 MONTHS
Secondary outcome [7] 326642 0
AF-RELATED KNOWLEDGE will be assessed by an extended version of the Atrial Fibrillation Knowledge Scale (Hendriks et al. Int J Cardiol, 2013)
Timepoint [7] 326642 0
Baseline, 6, 12, 24 MONTHS
Secondary outcome [8] 326643 0
QUALITY OF LIFE will be assessed by means of the SF-36 questionnaire as well as by the AF Effect on QualiTy of life survey (AFEQT), which specifically assess quality of life in patients with AF.
Timepoint [8] 326643 0
Baseline, 6, 12, 24 MONTHS
Secondary outcome [9] 326644 0
ANXIETY AND DEPRESSION will be assessed by means of the Hospital Anxiety and Depression Scale
Timepoint [9] 326644 0
Baseline, 6, 12, 24 MONTHS

Eligibility
Key inclusion criteria
Primary diagnosis of AF.
ECG or rhythm strip confirmation of AF.
Presenting to the emergency department, admitted to hospital, referred by their treating cardiologist or referred to the outpatient cardiology clinic, primarily due to AF
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Age <18 years or >90 years
History of myocardial infarction or coronary surgery within 3 months to enrolment
Valvular heart disease needing intervention
Left ventricular ejection fraction < 35%
Active malignancy defined as an active treatment with chemotherapy or radiotherapy, or related treatment < 3 months prior to enrolment.
Autoimmune or systemic inflammatory disease
Severe liver or renal dysfunction
Untreated hyperthyroidism
Pregnancy
Inability to provide informed consent
Not living independently

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients with a primary diagnosis of AF, presenting to the emergency departments or cardiology outpatient departments of the participating hospitals, or referred directly by their treating cardiologist, will be recruited. AF needs to be confirmed on ECG. Participants will be informed about the study, and after providing written informed consent, will be randomised either to the integrated AF management (active) group or the usual care (control) group. Allocation concealment will be performed by central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation between 0 (control) and 1 (active) using an electronic random number generator
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Follow-up for 24 months
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary (composite) endpoint of the study is survival time to first hospitalisation or death from any cause within two years from randomisation. A two-year cumulative incidence of 21% has been assumed in the standard care (control) group based on prior results (Hendriks et al. 2012).
The trial is powered to detect a 6% decrease in cumulative incidence in the integrated care (active) group using the log rank test with overall Type I error probability alpha=0.05 (two-sided) and power 1-beta=0.80 (one-sided). A minimum follow-up of two years from recruitment is planned. A 20% dropout rate per year in each group is assumed. Overall, the trial will enroll a minimum of 688 patients in each group, including a 10% increment to cover unexpected withdrawals, and asuming the study continues to completion. Thus, the total study population comprises 1376 patients.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/05/2018
Actual
12/05/2021
Date of last participant enrolment
Anticipated
10/05/2023
Actual
Date of last data collection
Anticipated
2/06/2025
Actual
Sample size
Target
1376
Accrual to date
43
Final
Recruitment in Australia
Recruitment state(s)
ACT,SA,VIC
Recruitment hospital [1] 3889 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 3890 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 3891 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment hospital [4] 6317 0
The Canberra Hospital - Garran
Recruitment hospital [5] 6469 0
The Alfred - Prahran
Recruitment hospital [6] 21671 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 9780 0
5000 - Adelaide
Recruitment postcode(s) [2] 9782 0
5042 - Bedford Park
Recruitment postcode(s) [3] 9783 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [4] 9785 0
2605 - Garran
Recruitment postcode(s) [5] 14024 0
3004 - Prahran
Recruitment postcode(s) [6] 36718 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 291422 0
University
Name [1] 291422 0
The University of Adelaide
Country [1] 291422 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
North Terrace
SA 5000 Adelaide
Country
Australia
Secondary sponsor category [1] 290099 0
Hospital
Name [1] 290099 0
Royal Melbourne Hospital
Address [1] 290099 0
Grattan St Parkvill VIC 3050
Country [1] 290099 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292975 0
Royal Adelaide Hospital Ethics Committee
Ethics committee address [1] 292975 0
Ethics committee country [1] 292975 0
Australia
Date submitted for ethics approval [1] 292975 0
24/03/2016
Approval date [1] 292975 0
12/08/2016
Ethics approval number [1] 292975 0
HREC/16/RAH/76

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 57850 0
Prof Prashanthan Sanders
Address 57850 0
Centre for Heart Rhythm Disorders
The Royal Adelaide Hospital-4G751
Port Road
Adelaide SA 5000
Country 57850 0
Australia
Phone 57850 0
+61 8 8222 2723
Fax 57850 0
Email 57850 0
[email protected]
Contact person for public queries
Name 57851 0
Prashanthan Sanders
Address 57851 0
Centre for Heart Rhythm Disorders
The Royal Adelaide Hospital-4G751
Port Road
Adelaide SA 5000
Country 57851 0
Australia
Phone 57851 0
+61 8 8222 2723
Fax 57851 0
Email 57851 0
[email protected]
Contact person for scientific queries
Name 57852 0
Prashanthan Sanders
Address 57852 0
Centre for Heart Rhythm Disorders
The Royal Adelaide Hospital-4G751
Port Road
Adelaide SA 5000
Country 57852 0
Australia
Phone 57852 0
+61 8 8222 2723
Fax 57852 0
Email 57852 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.