The primary objective of this study is to demonstrate that individually optimized, triple-site biventricular pacing is superior to standard biventricular pacing in reversing ventricular modeling as demonstrated by Echo Left Ventricle End-Systolic…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to demonstrate that individually
optimized, triple-site biventricular pacing is superior to standard
biventricular pacing in reversing ventricular modeling as demonstrated by Echo
Left Ventricle End-Systolic Volume (LVESV) at twelve months in patients with
non LBBB morphology without increasing the risk of serious procedure and/or
device related events at thirty days.
For the primary objective the primary efficacy endpoint is used, change in
LVESV at 12 months post-implant, comparing both groups in a superiority context
with an expected change of 12% between both groups.
The echo measures will be validated by an independent core lab, which will be
blinded to the randomization assignments.
The primary efficacy endpoint will be evaluated in a superiority format, with
statistical hypothesis tests formally defined in sections below.
For the primary safety endpoint, a patient*s clinical status will be evaluated
considering the incidence of serious procedure and/or device related events
assessed from the time of enrollment, during implant, through discharge and up
to thirty days follow-up.
Secondary outcome
The main secondary objectives of this study are:
- Evaluate reverse ventricular remodeling response based on echocardiographic
measures at six and twelve months follow-up
- Assess clinical outcome using NYHA classification, at thirty days, six and
twelve months after treatment compared to the baseline evaluation.
- Evaluate mortality and serious heart failure (HF) events during the procedure
through discharge and at the different follow-up time-points.
- Evaluate serious device related complications at six and twelve months
post-procedure.
The main secondary objectives will be based on the secondary endpoints as
described in section 8.1.2.
Change in LV volumes and LV ejection fraction will be evaluated as part of
reverse remodeling response, based on echocardiographic measurements:
o LVESV at 6 months
o LVEDV at 6 and 12 months
o LVEF at 6 and 12 months
Analysis will be done for patients were echocardiographic data are available at
baseline and six and/or twelve month follow-up.
The echo measures will be validated by an independent core lab.
A patient*s clinical status will be evaluated considering:
o NYHA functional class improvement - The evaluation of the NYHA classification
consists of reporting the percentage of patients who improved at least one NYHA
class at each follow-up post-implant.
o Death from any cause - The reporting of deaths occurred consists of the
percentage of dead patients, the causes of death, the time to death and
survival curves.
o HF-related hospitalizations, as defined in section 15.4.
o The incidence of serious device related events assessed at six and twelve
months.
A safety assessment will be performed, including all reported events collected
for all enrolled patients.
Background summary
Cardiac resynchronization is a recommended therapy for patients with advanced
heart failure, under optimized medical treatment with reduced left ventricular
ejection fraction and prolonged QRS. It reduces morbidity and mortality, and
induces reverse left ventricular remodeling. Implantation of a standard
biventricular therapy is today a Class I indication in LBBB patients under
optimized medical therapy.
Nevertheless, still 30% of the population do not respond to standard
biventricular implantation. Alternative RV stimulation sites (septal) have not
showed substantial benefit over classical RV apical.
An individual patient meta-analysis showed benefit from CRT when QRS duration
exceeds a threshold value of 140 ms. The importance of QRS morphology over QRS
duration is supported by results of recent large scale randomized trials
showing the absence of clear benefit of standard biventricular implantation in
populations of non-LBBB patients, although significant numbers of individuals
do take advantage. Similar individual benefit has also been shown even in
narrow QRS patients at the condition that preexisting mechanical dyssynchrony
was recorded prior to implantation.
Nevertheless, the present status of biventricular therapy (dyssynchrony
identification and implantation process) does not take into account mechanical
approach, and as a consequence, in the most recent international guidelines4,5,
non-LBBB patients have been *downgraded* from Class I to Class IIa for QRS >
150 ms and to Class IIb for QRS between 120 and 150 ms. Patients with narrow
QRS are not candidates for the therapy.
The frequent failure of CRT in non-LBBB patients is suspected to be due to more
complex and heterogeneous forms of electrical/mechanical dyssynchronies needing
more complex and individualized pacing configurations to be corrected.
Study objective
The primary objective of this study is to demonstrate that individually
optimized, triple-site biventricular pacing is superior to standard
biventricular pacing in reversing ventricular modeling as demonstrated by Echo
Left Ventricle End-Systolic Volume (LVESV) at twelve months in patients with
non LBBB morphology without increasing the risk of serious procedure and/or
device related events at thirty days.
For the primary objective the primary efficacy endpoint is used, change in
LVESV at 12 months post-implant, comparing both groups in a superiority context
with an expected change of 12% between both groups.
The echo measures will be validated by an independent core lab, which will be
blinded to the randomization assignments.
The primary efficacy endpoint will be evaluated in a superiority format, with
statistical hypothesis tests formally defined in sections below.
For the primary safety endpoint, a patient*s clinical status will be evaluated
considering the incidence of serious procedure and/or device related events
assessed from the time of enrollment, during implant, through discharge and up
to thirty days follow-up.
Study design
This is a multicenter, international, prospective, randomized, superiority,
open label study.
The efficacy endpoint for this study is the change in LVESV at twelve months
post-implant between individually optimized, triple-site biventricular pacing
and standard biventricular pacing.
LVESV is a standard marker of CRT effectiveness1. Echocardiographic data
collected at twelve months follow-up will document the evolution of LVESV as
compared to baseline in order to assess reverse ventricular remodeling. The
echo measures will be validated by an independent core lab.
The safety endpoint for this study is the rate of all serious procedure and/or
device related events reported at thirty days post-implant. Events will be
reviewed and adjudicated by an independent Clinical Events Committee.
Intervention
Group 1 : implantation triple site biventricular ICD
Group 2: implantation dual site biventricular ICD
Study burden and risks
No additional risk.
Paasheuvelweg 1
Amsterdam 1100 AE
NL
Paasheuvelweg 1
Amsterdam 1100 AE
NL
Listed location countries
Age
Inclusion criteria
Heart failure NYHA II, III, ambulatory IV
LVEF <35%
QRS >140 ms
Non-typical LBBB morphology
Exclusion criteria
Unstable heart failure
Permanent AF
Unstable angina, MI, CABG, PTCI in last 90 days
Renal failure GFR <30ml/min/1.37m2
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 | NCT02350842 |
| CCMO | NL52374.075.15 |