Reversal of Atrial Substrate to Prevent Atrial

Atrial Fibrillation Clinical Trial

— RASTA AF  

Official title:

Reversal of Atrial Substrate to Prevent Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03682991
• Other study ID #: RP-007
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2019
• Est. completion date: December 2026

Study information

• Verified date: February 2024
• Source: Nova Scotia Health Authority
• Contact: Ratika Parkash, MD FRCPC
• Phone: 902-474-4474
• Email: Ratika.Parkash[@]nshealth.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A multi-center, randomized trial to examine the effect of aggressive risk factor control and arrhythmia trigger-based intervention on recurrence of atrial fibrillation.

Description:

Atrial fibrillation (AF) is a major health problem, with a prevalence of 0.4-1% of the population. It results in high healthcare costs and significant morbidity, especially for patients with severe symptoms. Exercise and risk factor modification to prevent and modify AF has garnered a significant amount of support in cohort studies that have proven benefit. It is well known that age, body mass index, valvular heart disease, heart failure, hypertension and sleep apnea are risk factors for AF, most of which are modifiable if targeted appropriately. In addition, catheter ablation techniques have evolved and improved to reduce AF recurrence in those who are most symptomatic, and either have heart failure, or are at risk for its development. Despite these advances, the recurrence of AF remains high.

We propose to determine whether early treatment of the arrhythmogenic substrate, with or without aggressive risk factor modification, is most important in prevention of recurrent AF. It is hypothesized that patients with underlying risk factors that promote AF will benefit most from a combined strategy of aggressive risk factor modification in combination with catheter ablation.

The study design will be a two-arm, parallel group, randomized clinical trial comparing catheter ablation versus catheter ablation plus aggressive risk factor therapy, followed by maintenance with blinded endpoint evaluation. Patients with symptomatic AF and two of the following will be included: hypertension, BMI≥27, diabetes, prior stroke/TIA, history of heart failure (prior heart failure admission due to AF or LVEF<40%), age≥65. Patients will be excluded if they are exercising >150 minutes/week by self-report. Patients will be randomly allocated to one of the following groups: 1) AF ablation within 3 months, 2) AF ablation at 3 months, with a 12 week home-based exercise/risk factor management program, followed by maintenance therapy. A 5 month treatment period will be observed to deliver the interventions and have a 2 month blanking period post ablation. Guideline-directed therapy for risk factors will occur in all groups, including BP, cholesterol, diabetes, alcohol reduction and sleep apnea screening. All patients will undergo implantation of an implantable loop recorder (ILR) at baseline. The primary outcome will be a composite of death at any time, AF-related hospitalization/emergency department visits and AF >24 hours (5 months post randomization). Secondary outcome will include AF burden. The sample size required is 670.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 670
• Est. completion date: December 2026
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: Patients with symptomatic (CCS-SAF =2) paroxysmal or persistent atrial fibrillation despite rate control, desiring catheter ablation and at least two of the following:

• BMI>27,

• BP>140/90 mmHg or history of hypertension,

• Prior stroke/transient ischemic attack,

• Diabetes,

• Heart failure (prior heart failure admission or left ventricle ejection fraction (LVEF) <40%),

• Age = 65 years.

Exclusion Criteria:

• Left atrial size > 5.5 cm,

• New York Heart Association (NYHA) Class IV (Severe) heart failure,

• Participation in a cardiac rehabilitation program within the last year,

• Currently performing exercise training >150 minutes/week of moderate to vigorous physical activity,

• Unable to exercise,

• Unable to give informed consent,

• Other noncardiovascular medical condition making 1 year survival unlikely,

• Less than 18 years of age.

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Other:
• Aggressive Risk Factor Control
Sleep apnea screening, therapy is recommended if apopnea-hypopnea (AHI) index is greater than 15, with a target index of less than 5. Counseling regarding alcohol reduction to 2 drinks/day for men, 1 drink/day for women, no binge drinking (>5 drinks at one setting). Participation in a 12 week structured, home-based exercise program and nutritional counseling. Weight reduction will be emphasized through modification of diet and exercise. Blood Pressure management to achieve a target systolic blood pressure (SBP) of <120/80 mm/Hg Smoking cessation facilitated through local resources already established at each site
• Standard of Care
Recommendations based on current guidelines

Locations

Country	Name	City	State
Canada	QE II Health Sciences Centre	Halifax	Nova Scotia

Sponsors (4)

Lead Sponsor	Collaborator
Nova Scotia Health Authority	Abbott, Canadian Institutes of Health Research (CIHR), Ottawa Heart Institute Research Corporation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of ablation procedural complications [Safety]	Periprocedural complications will be assessed.	up to 48 months
Other	Number of antiarrhythmic drug adverse effects [Safety]	Adverse drug reactions will be assessed.	up to 48 months
Other	Exercise compliance - IPAQ	Compliance to exercise recommendations will be measured by the International Physical Activity Questionnaire (IPAQ) which calculates a metabolic equivalent (MET) score by asking participants the days and minutes exercised in three categories of intensity (vigorous, moderate, and walking) during the previous one week. MET values are as follows: walking = 3.3, moderate activity = 4, vigorous activity = 8). Results will be reported as a continuous variable (MET minutes a week) calculated by multiplying the MET value by the minutes the activity was carried out and the number of days the activity was undertaken. MET minutes achieved in each category will be added to get the total MET minutes of physical activity a week.	up to 24 months
Other	Sleep apnea therapy compliance	Apopnea-hypopnea index (AHI) as measured on a continuous positive airway pressure (CPAP) machine. AHI is calculated by dividing the number of apnea events by the number of hours of sleep. AHI values for adults are: normal (AHI<5); mild (5=AHI<15); moderate (15=AHI<30) and severe (AHI=30)	up to 48 months
Other	Systolic Blood pressure target achievement	Assessed at each follow up to determine if the target SBP of <120/80 mm/Hg has been achieved.	up to 48 months
Primary	Number of AF related hospitalizations post ablation	AF-related hospitalizations (lasting more than 24 hours) from 2-months post ablation to end of follow up.	up to 48 months
Primary	Number of AF related Emergency Department (ED) visits post ablation	AF-related emergency department visits from 2-months post ablation to end of follow up.	up to 48 months
Primary	Number of clinically significant AF events post ablation	Clinically significant AF events lasting >24 hours (either an irregular R-R interval, or atrial cycle length < 280 ms, as obtained from an insertable cardiac monitor) from 2-months post ablation to end of follow up.	up to 48 months
Secondary	Number of AF-related hospitalizations	AF-related hospitalizations (lasting more than 24 hours) from randomization to end of follow up.	up to 48 months
Secondary	Number of AF-related emergency department (ED) visits	AF-related emergency department visits from randomization to end of follow up.	up to 48 months
Secondary	Number of Clinically significant AF events	Clinically significant AF events lasting >24 hours (either an irregular R-R interval, or atrial cycle length < 280 ms, as obtained from an insertable cardiac monitor) from randomization to end of follow up.	up to 48 months
Secondary	Mean AF burden	Average percentage of time in AF during follow up, as measured by insertable cardiac monitor.	up to 48 months
Secondary	Stroke or systemic embolism events	Total number of stoke or systemic embolism events.	up to 48 months
Secondary	Quality of Life - CCS-SAF	Symptom burden as measured by the Canadian Cardiovascular Society (CCS) Severity of Atrial Fibrillation (SAF) scale. CCS-SAF scores range from 0 to 4, with higher values representing more severe impact of symptoms on quality of life and activities of daily living.	Up to 24 months
Secondary	Quality of Life - AFEQT	Quality of life as measured by the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) scale. The scale consists of 21 questions with 7-point Likert scale responses. Questions 1-18 are grouped into three subscales (symptoms, daily activities and treatment concern). Questions 19-21 capture satisfaction with treatment and are not include in the HRQoL score of the questionnaire. Overall and subscale scores range from 0 to 100. Lower scores correspond to higher levels of disability (e.g., 0 corresponds to complete disability or responding "extremely" limited, difficult or bothersome to all questions answered), while a score of 100 corresponds to no disability (e.g., responding "not at all" limited, difficult or bothersome to all questions answered). For Satisfaction questions, a score of 100 corresponds to extreme satisfaction with current treatment.	Up to 24 months
Secondary	Number of recurrent AF-ablations	Number of re-ablations required.	up to 48 months
Secondary	Cardioversions	Number of cardioversions required.	up to 48 months
Secondary	All-cause mortality	Any deaths occurring at any time during the study.	up to 48 months