Primary ObjectiveTo determine if an approach consisting of AV junction ablation and biventricular pacing is superior to optimal pharmacological rate control therapy in reducing total mortality at 48 months.Secondary ObjectiveTo determine if an…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Total mortality at 48 months
Secondary outcome
At 48 months a combined endpoint of cardiovascular mortality and
hospitalization for heart failure or uncontrolled intolerable AF
Background summary
Atrial fibrilation may be associated with other co-morbidities, especially
heart failure. In these cases, while pharmacological ventricular rate control
may be the first objective, adequate doses of vasoactive medications may not be
tolerated and antiarrhythmic medications or ablation to
help with rhythm control may be contraindicated or ineffective. In these cases,
atrioventricular (AV) junction ablation and cardiac pacing is an
alternative treatment option. AV junction ablation, by slowing and regularizing
the ventricular rate, has been shown to improve symptoms, quality of life, and
cardiac function.
While rate control is achieved with AV junction ablation, ventricular
dyssynchrony caused by chronic right ventricular pacing may adversely affect
heart function and impede the salutary effects of rate control and rate
regularization. Recent trials suggest that biventricular pacing may counteract
the adverse effects of non-physiological right ventricular pacing. In
particular, in the APAF study, CRT proved superior to conventional right
ventricular apical pacing in reducing the clinical manifestations of heart
failure (hospitalization and worsening heart failure) *on top* of rate
regularization achieved by means of AV junction ablation. The beneficial effect
of CRT was consistent both in patients who met the current recommendations for
CRT and those who did not.
Evidence of superiority of AV junction ablation strategy as opposed to optimal
pharmacological rate control therapy exists only for symptoms of AF, but not
for heart failure occurrence, hospitalization, morbidity and mortality. Thus,
both strategies are currently recommended by guidelines and the choice between
them is left to physician*s preference. The need for a comparison between
pharmacological and non-pharmacological strategy represents the rationale of
the APAF-CRT trial.
Study objective
Primary Objective
To determine if an approach consisting of AV junction ablation and
biventricular pacing is superior to optimal pharmacological rate control
therapy in reducing total mortality at 48 months.
Secondary Objective
To determine if an approach consisting of AV junction ablation and
biventricular pacing is superior to optimal pharmacological rate control
therapy in reducing at 48 months a combined endpoint of cardiovascular
mortality and hospitalization for heart failure or uncontrolled intolerable AF.
Study design
This is a one-to-one randomized, multicenter, prospective study consisting of
twoconsecutive overlapped phases: the Morbidity trial (closed) and the
Mortality trial.
Patients will be randomized to AV junction ablation and biventricular pacing
(Study Arm) vs. optimal pharmacological rate control therapy (Control Arm).
Randomization will be stratified by center and by baseline EF (35% and >35%).
Subjects will be followed for a maximum period of 4 years with required yearly
visits. At each follow-up visit data about clinical events and healthcare
utilization will be collected. Additionally, at 1 year the symptomatic status
will be assessed.
Intervention
Patients assigned to the Study Arm will undergo surgical procedures to receive
an AV junction ablation and biventricular pacing.
Study burden and risks
Both strategies (i.e. AV junction ablation plus biventricular pacing and
optimal pharmacological rate control therapy) are currently recommended by
guidelines and the choice between them is left to physician*s preference. Thus,
it is not anticipated that patients enrolled in this study will be exposed to
any risks beyond those normally encountered in clinical practice. All risks and
risk mitigation strategies are listed below.
A. Summary of Risks
It is not anticipated that patients randomized to the Study Arm will be exposed
to any additional risks beyond risks normally associated with ablation
procedures, CRT systems, transvenous leads, and their implant. However, there
may be additional risks related to study participation that are unknown at this
time.
B. Minimization of Risks
Risks will be minimized by selecting physicians who are experienced in the
implantation of these devices and in the diagnosis and treatment of patients
with arrhythmias and/or heart failure. In addition, investigators will be
trained on the protocol requirements.
Benefit
The approach consisting of AV junction ablation and biventricular pacing may be
superior to optimal pharmacological rate control therapy in reducing mortality
due to heart failure, hospitalization for heart failure or uncontrolled
intolerable AF, worsening heart failure.
Since the risks are practically zero and the benefits can be life saving, we
are convinced that the conduction of the trial is justified.
If deemed potentially effective, AV junction ablation and CRT will not be
precluded to patients in the Control arm (ethical issue). Investigators are
allowed to consider the cross-over from Study Arm to Control Arm for those
patients who have reached the primary endpoint, thus after
demonstration of further deterioration in clinical status. However, cross-over
per se will not be considered as endpoint in analysis.
Via don Bobbio /
Lavagna 16033
IT
Via don Bobbio /
Lavagna 16033
IT
Listed location countries
Age
Inclusion criteria
a) Permanent AF (> 6 months) which has been considered unsuitable for AF
ablation or which resulted in failed AF ablation;
b) Severely symptomatic (AF-related symptoms), refractory to drug therapy
for rate control;
c) QRS duration * 110 ms;
d) At least one hospitalization related to AF and/or heart failure in the
previous year (see definition in section IV. Statistical Methods and Data
Analysis in protocol);
Exclusion criteria
a) Patient is less than 18 years of age;
b) NYHA class IV and systolic blood pressure * 80 mmHg despite optimal
therapy;
c) Myocardial infarction within the previous 3 months;
d) Previously implanted cardiac devices (pacemaker/ICD/CRT) with *5%
pacing function. Patients who had devices implanted that had <5% of paced beats
(i.e., back*up
pacing) can be enrolled;
e) Severe concomitant non-cardiac disease;
f) Need for surgical intervention. (Cardiac surgery is scheduled)
g) Patients with LVEF >50% are excluded
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02137187 |
| CCMO | NL70784.068.19 |