ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12613000444785

Ethics application status

Not yet submitted

Date submitted

3/04/2013

Date registered

18/04/2013

Date last updated

8/03/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

Implications of aggressive cardiac risk factor management on the catheter ablation for atrial fibrillation

Scientific title

Implications of aggressive cardiac risk factor management on the catheter ablation for atrial fibrillation

Secondary ID [1]

NIL

Universal Trial Number (UTN)

Trial acronym

ARREST -AF

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Metabolic Syndrome

Atrial Fibrillation

Condition category

Condition code

Diet and Nutrition

Obesity

Cardiovascular

Other cardiovascular diseases

Metabolic and Endocrine

Metabolic disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The study will be a multi-center prospective randomized controlled study evaluating the effect of a structured weight and cardio-metabolic risk factor management program on multiple outcomes pertinent to Atrial Fibrillation. The project will incorporate two distinct studies with respective primary and secondary outcomes.

Phase 1 will primarily assess the impact of intervention on objectively measured AF burden and electroanatomical remodelling and or reverse remodelling of heart along with autonomic and thrombotic parameters.This will be first 6 months after enrolment.

Phase 2 will evaluate the impact of intervention on success of catheter ablation along with autonomic and thrombotic parameters and will be from time of ablation until 60 months.
The two phases of the program, weight loss and weight maintenance, will follow a previously described approach.

This regime has been successfully used by another study from our group and was assessed and approved by the RAH REC.

Weight loss will be achieved by using structured physician-led motivational and goal-directed face-to-face visits every 3 months. In addition, patients will be encouraged to utilize support counseling and schedule more frequent reviews, as they required. The intervention cohort will be subjected to periodic intensive one-on-one supportive counseling that will review goals achieved and further incremental goal setting. Nutritional behavior reflection, barriers to goal achievement and nutritional decision coaching will be the pillars of the 20-40 minute counseling sessions. Subsequent to barrier identification, verbal and written tailored educational material will be provided. The participant could schedule additional intervening visits and/or physician at will in the event of an impending relapse. When additional support is required, 24-hour email and telephone contact will be available.

Initial weight reduction will be attempted by a meal plan and behavior modification program. Participants will be required to maintain a diet and activity diary. Meals will consist of high protein and low glycemic index, calorie controlled foods. If the patients did not loose 3% of weight after first 3 months they will then be prescribed very-low-calorie meal replacement sachets (Prima health solutions or Nestle Health Science) for 1-2 meals a day. The initial goal will be to reduce body weight by 10% from baseline. Patients on meal replacement supplement will undergo weight loss in two distinct phases.

Weight loss phase : Weight loss will be induced over 8 weeks using a modified very low calorie diet (VLCD) (800-1200 Cal/day). Patients will be prescribed VLCD meal replacement diet for 1-2 of their daily meals. Remaining meal will consist of high animal and plant protein, and low glycemic index (GI), calorie controlled foods.

Weight maintenance phase : After patients achieved initial goal the meal replacement will be replaced with high protein and low glycemic index, calorie controlled foods. Further weight loss with diet will be attempted if indicated with a target BMI of 25 kg/m2. This phase will focus on slower weight loss and maintenance. This will occupy the remainder of the follow up period. During this phase, VLCD meal supplements will be gradually phased out and replaced with a low GI meal plan with emphasis on education for permanent lifestyle changes and behavior modification program.

Lifestyle Journal - Participants in the intervention group only are instructed to maintain a self-monitoring lifestyle journal detailing food type, preparation method and amount consumed. Patients are advised to review the journal on a weekly basis on their own and to reflect on nutritional behavioral patterns. The journal functions to indicate, in addition to nutritional habits, blood pressure patterns (documented 2-3 times daily, see below) and estimated energy expenditure. The maintenance of the journal is a dynamic process, whereby it may be relaxed when significant clinical (and anthropometric) progress is made and re-initiated when healthy lifestyle divergence is evident or a weight re-gain is impending.

Exercise – In the intervention group, physical activity is prescribed initially at 20 minutes of low intensity (walking and/or aqua-aerobics) thrice weekly and titrated over phase 1 to reach 45 minutes thrice weekly finally increasing to at least 200 min of moderate-intensity physical activity in a week. Type of activity and duration is logged into the journal. Control group participants are not required to maintain a lifestyle journal and education regarding activity levels is issued in the form of specific written material. Low intensity exercise was prescribed initially for 20 minutes thrice weekly

Control Group - Standard care (control) group participants are issued with once off written and verbal advice regarding health nutrition and exercise guidelines at commencement of their participation and weight management is a self-directed process. Completion of a diet and activity diary was not requested. Follow-up will scheduled three monthly for a 20-40 minute physician-led major assessment, as for the intervention group.

Cardio-metabolic risk assessment and managements (All Groups) - Coexistent risk factors of hypertension, hyperlipidemia, glucose intolerance, obstructive sleep apnea, alcohol and tobacco use are identified through historical patient records and fasting plasma testing (see below). Following identification, optimal management in accordance with current established best practice guidelines is undertaken by the identifying physician and by referral to a specialist management clinic (diabetes and sleep disordered breathing) for that particular risk factor. Both intervention and control cohorts undergo comprehensive risk assessment and management.

Glucose tolerance and hyper-insulinemia -If fasting glucose was between 100 and 125mg/dL, a 2-hour oral glucose tolerance test will be performed. Impaired glucose tolerance (IGT) will be managed with lifestyle measures such as diet and aerobic exercise. If patients were unable to maintain glycosylated hemoglobin values below 6.5 percent after three months, metformin will be started. Patients in both groups with poor glycemic control (HbA1c>7%) will be referred to diabetes clinic.

Hyperlipidemia – Management of dyslipidemia will be in accordance with the guidelines. Initial management will be with lifestyle measures. If patients were unable to achieve LDL-Cholesterol of less than 100mg/dL after 3 months then statin will be initiated. Fibrates will be used for isolated cases of hypertriglyceridemia (TG > 500mg/dL) or added to statin therapy if TG> 200mg/dL and non-HDL cholesterol was >130mg/dL after 3 months of therapeutic life style changes.

Hypertension – Patients in RF Mx or intensive arm group will be asked to measure blood pressure (BP) twice daily using home-automated monitor and an appropriate sized cuff. 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, in keeping with current guidelines. 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 on at least 80% of random patient acquired blood pressure readings as listed above. These will also be corroborated by in-office readings and 24-hour ambulatory blood pressure monitors as required. In addition, echocardiography be be used to monitor and to ensure the resolution of any left ventricular hypertrophy as objective evidence of end-organ injury. Changes in the dose and number of anti-hypertensive agents will be recorded at each 3 monthly visit.

Sleep apnea - All subjects will be referred to the same dedicated sleep disorders unit for inpatient or home overnight polysommnography. Continuous positive airway pressure will be prescribed in the presence of a clinically compatible history of sleep apnea and sleep study results (RDI and desaturation levels). Generally, for an RDI of 15-30 continued lifestyle measures may be pursued with periodic evaluation and for an RDI >30, CPAP will be prescribed.

Smoking: The “5A” (Ask, Assess, Advice, Assist and Arrange follow up) structured smoking cessation framework was adapted. Smokers were offered help and follow-up, with access to clinic for behavioral support.

Alcohol: Written and verbal counseling was provided with regular supportive follow up for alcohol reduction (=2 drinks for men and =1 for female) with abstinence as ultimate goal.

Pharmacotherapy – Major clinical review, assessment of lifestyle journal and 12-lead ECG will be performed on all enrolled patients. Patient response and tolerance of all prescribed pharmacotherapy will be assessed. Medication addition, cessation and dosage titration is undertaken and documented at each 3-month visit. Anti-arrhythmic medications, for rate and/or rhythm control will be prescribed at the discretion of the attending physician and guided by the clinical response and symptomatology of the patient. Electrical cardioversion may be performed as a last resort, in preference for pharmacologic cardioversion.

ABLATION PROCEDURE

There is no alteration of the clinical procedure as part of the study protocol.
All patients less than 65 yrs. old will undergo Electrophysiology study to rule out supra ventricular tachycardia (SVT) as a cause for atrial fibrillation (Standard Practice in RAH) If found then this tachycardia will be ablated. At a later date if the patient needs AF ablation, an EP study will be done with activation mapping of both atrium and then wide encircling pulmonary vein antrum isolation will be performed with the aid of electroanatomic mapping and 3-D LA geometry construction. Radiofrequency current from irrigated tip catheters will be the used as the ablation energy. A stepwise approach to LA ablation, with linear lesion formation, coronary sinus isolation and possible fractionated electrogram targeting, will be utilised based on the discretion of the operator. This is based on the frequency and duration of attacks and chronicity of the disease. Pre-procedural anti-coagulation will be managed in accordance with local guidelines.
Within the 60 months of follow-up, patients may undertake a repeat or consolidative AF procedure as clinically required.
Post Ablation Care : Anticoagulation management will be as for standard clinical care, using post procedural heparin, flowed by enoxaparin while warfarin loading takes place.

During the follow-up visits, patients will undergo face-to-face counseling and feedback based on anthropometric measures and lifestyle journal. Patients will have access to 24 hour email and telephone support in addition to additional counseling sessions if required. The periodicity of follow-up data recording is as follows: 1:Follow up review (40 min) every 3 months in both groups.In intensive arm this can be more frequent if required. 2.BMI, Waist Circumference(WC), blood pressure, 12-lead ECG (baseline and three monthly) 3.7 day Holter recording (baseline and 12 months,24months,36months,48months,60months) 4.Exercise stress testing (baseline and 12 months,24months,36months,48months,60months) 5.Head up tilt table testing (baseline and 12 months,24months,36months,48months,60months) 6.Transthoracic echocardiography (baseline and 12 months,24months,36months,48months,60months) 7.Delayed enhancement Cardiac MRI (baseline and 12 months,24months,36months,48months,60months) 8.Fasting plasma biochemistry (baseline and 12 months,24months,36months,48months,60months)

Intervention code [1]

Treatment: Surgery

Intervention code [2]

Prevention

Intervention code [3]

Lifestyle

Comparator / control treatment

Standard care (control) group participants are issued with once off written and verbal advice regarding health nutrition and exercise guidelines at commencement of their participation and weight management is a self-directed process. Follow-up will scheduled three monthly for a 20-40 minute physician-led major assessment, as for the intervention group.Total follow up will be for 60 months

Control group

Active

Outcomes

Primary outcome [1]

*AF burden on loop recorder before AF ablation(%)

Timepoint [1]

Baseline, 3, 6, 9, 12 ,24,36,48,60 MONTHS

Primary outcome [2]

*Percentage of patients free from AF on loop recorder after AF ablation. The AF burden will be assessed by loop recorder data.

Timepoint [2]