Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05514860 |
| Other study ID # |
H16-00617_SRG-15-P15-001 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 2017 |
| Est. completion date |
November 2022 |
Study information
| Verified date |
October 2022 |
| Source |
University of British Columbia |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The PROGRESSIVE-AF Trial is a national, multi-center randomized controlled trial comparing
early ("first-line") catheter-based pulmonary vein isolation (PVI) using cryothermal energy
to first-line anti-arrhythmic drug therapy. The aim of the trial is to evaluate if the
initial treatment choice (ablation vs. pharmacotherapy) influences AF disease progression, as
measured by continuous cardiac monitoring. The outcomes of interest are disease progression,
quality of life, and healthcare utilisation. The targeted population consists of healthy
patients with symptomatic paroxysmal AF without clinically significant heart diseases aged
between 18 and 75 years. This study represents a new research project leveraging the existing
EARLY-AF randomised clinical trial infrastructure to examine the novel endpoints of: 1)
disease progression ("time to first episode of persistent AF"), 2) progressive AF burden ("%
time in AF"), 3) Quality of Life, and 4) healthcare utilisation at 36 months of follow-up.
Description:
Project Aim: Atrial fibrillation is a major burden to healthcare systems. Contemporary costs
of managing AF have been estimated to be up to 2.7% of total annual healthcare expenditures.
A significant proportion of these expenses result from the direct costs associated with
hospitalization and acute care. The CANet funded EARLY-AF Study aimed to determine whether
EARLY invasive intervention resulted in a significant (i.e. >20%) reduction in arrhythmia
recurrence and health care utilisation at one year of follow-up. The PROGRESSIVE AF study
aims to evaluate the long-term effect of EARLY invasive intervention on disease progression
and health care utilisation.
Project Background: Atrial fibrillation (AF) is a chronic progressive disease characterized
by exacerbations and remissions. Early on, AF is triggered by one or more ectopic foci in the
atria and is perpetuated via micro re-entrant circuits in the atrial body or at the pulmonary
venous-left atrial junction. With recurrent episodes the atria undergoes electrical,
contractile, and structural remodelling resulting in a greater predisposition toward
sustained arrhythmia. This results in the progression of incidental and paroxysmal
(self-terminating) AF to persistent (AF requiring intervention for termination) and
eventually permanent AF (recurrent AF of >1 year in duration for which cardioversion was
unsuccessful). While anti-arrhythmic drugs (AADs) remain the "first-line" therapy, these
medications have only modest efficacy at maintaining sinus rhythm over the long term.
Moreover, these agents are associated with significant non-cardiac side-effects (e.g. heart
failure or organ toxicity), as well as the potential for pro-arrhythmia (i.e. increased
propensity towards malignant arrhythmias). Conversely, multiple randomized controlled trials
have demonstrated that catheter ablation is superior to drug therapy in maintaining sinus
rhythm when AADs have been ineffective, are contra-indicated or cannot be tolerated.
While the evidence to date has demonstrated the universal superiority of ablation over AAD
therapy, these studies have focused on medically refractory patients with more advanced forms
of AF. While it has been postulated that early invasive intervention with catheter ablation
may be beneficial, this assertion remains only hypothesis generating. As such we undertook
the CANet funded EARLY-AF program. This multicenter collaboration sought to determine if an
early invasive approach centered on cryoballoon based PVI was associated with a significant
(i.e. >20%) reduction in arrhythmia episodes, AF symptoms, and healthcare utilization at one
year of follow-up (i.e. the standard definition of success, as advocated by the Heart Rhythm
Society).
In recent years attention has turned to longer-term effectiveness and safety outcomes,
focusing more on the durability of catheter ablation procedures. Given that catheter ablation
is being offered to relatively young and otherwise healthy patients as a first-line treatment
approach, a comprehensive assessment of long-term clinical effectiveness is of particular
importance with respect to informed decision-making. Moreover, a comprehensive understanding
of the downstream effects of ablation greatly informs the evaluation of the
cost-effectiveness of invasive AF ablation procedures.
The PROGRESSIVE AF project aims to leverage the infrastructure established with the EARLY-AF
study to determine whether an a first-line invasive approach can alter the progressive
pathoanatomical changes associated with AF, and by extension alter the disease trajectory
(i.e. reduction in progression to persistent AF). The purpose of the current application is
to undertake a 3 year follow-up study in order to better understand: 1) the natural history
of AF (e.g. disease progression), 2) the relative ability of the two "first-line" treatment
approaches to alter disease progression (e.g. AAD vs. pulmonary vein isolation), 3) the
longer-term healthcare utilization associated with these two first-line treatment approaches,
4) the longer-term impact of these first-line approaches on patient reported outcomes.
Project Hypothesis, Research Question(s) and Objectives:
The majority of studies demonstrating the superiority of catheter ablation over
anti-arrhythmic drug therapy have focused on medically refractory patients. This design
pre-selects a group in whom medical therapy has been proven to be an ineffective therapy, and
weights the benefit significantly towards the ablation arm. To date it is unknown whether the
benefit of catheter ablation will be as substantial when delivered prior to medication
failure (i.e. as a "first-line" ablation strategy). Moreover, it is unknown whether
"first-line" ablation can alter the natural history of atrial fibrillation.
Project Hypothesis: We hypothesize that early intervention with the cryoballoon as a
"first-line" therapy will favourably alter the natural history of AF when compared to an
approach of "first-line" antiarrhythmic drug therapy. Specifically, we hypothesize that
"first-line" ablation will result in increased freedom from recurrent arrhythmia, reduced
need for pharmacologic or invasive intervention, reduced hospital utilisation due to symptoms
caused by documented atrial arrhythmias, as well as a reduced progression from paroxysmal to
persistent or permanent AF.
Objectives: The study is designed to evaluate of the impact of the early invasive management
of AF with the Arctic Front cryoballoon. The primary objective of the study is to evaluate
whether a "first-line" ablation strategy can reduce the progression from paroxysmal to
persistent AF over ~36 months of follow-up, as detected by continuous cardiac monitoring. The
secondary objective of the study is to evaluate the burden of AF on follow-up, as well as the
health related quality of life (HRQOL) impact associated with early invasive intervention, in
comparison to primary AAD therapy. This analysis will be centered on an evaluation of generic
and disease-specific HRQOL instruments in order to determine the impact of an early invasive
approach. The tertiary objective of the study is to evaluate the economic impact of early
invasive intervention, with a focus on healthcare utilization. These will be used to derive a
summary measure of health outcome and to inform subsequent healthcare resource allocation
decisions.
