The study is designed to substantiate the efficacy of CCM in the heart failure population with ejection fraction ranging between 25 and 45%. The study is designed in an adaptive manner to ensure proper statistical significance and power of the…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primarv endpoint:
Comparison between the groups of change in V02 max from baseline to 24 weeks of
follow-up.
VO2max will be evaluated by cardiopulmonary stress test (CPX), in a double
assessment (i.e., tests will be repeated twice at each study follow-up - the
two evaluations can be up to 2 weeks apart).
Secondary outcome
Secondarv endpoints:
Efficacv Comparison between the groups of:
* Change in quality of life as measure by Minnesota Living With Heart
Failure Questionnaire (MLWHFQ), from baseline to 24 weeks.
* Change in NYHA class, from baseline to 24 weeks
* Change in V02max from baseline to 24 weeks for each of the following
subgroups separately: Baseline EF <35% , baseline EF >35%
Other endpoints - exoloratory: Change in SHFM and MAGGIC survival prediction
model scores from baseline to 6 month of follow-up.
Safetv endpoints:
Comparison between the groups of:
* All-cause mortality
* Cardiovascular mortality
* Time to first event - cardiovascular related (death, LVAD, urgent heart
transplant or unplanned heart failure hospitalization)
* Time to first event - all cause (death or unplanned hospitalization)
Background summary
The OPTIMIZER* System is CE marked, compliant with all relevant regulations and
standards and is commercial (not investigational) in countries that accept the
CE Mark. This study will collect efficacy data in a randomized controlled
setting, including NYHA class II and III Heart Failure population with baseline
ejection fraction of 25% to 45%. There is previous evidence related to the
beneficial effect of CCM in patients with baseline ejection fraction of <35%.
While patients with EF between 35% and 45% were not prospectively studied in
the original clinical study initially conducted to support CE Marking of the
OPTIMIZER System, recently available data from a randomized study that included
such patients show CCM to be safe and effective in this group of patients as
well. Furthermore, the literature supports that this population has very
similar clinical characteristics, in practice are treated with nearly the same
medications, and have similar underlying mechanisms of disease compared to
patients with EF <35%. CCM has been successfully used also in patients with EF
greater than 35% in routine use and in the FIX-HF-5 study. Since the system is
CE marked and since the population includes patients meeting the approved
indication as well as population that has shown to benefit from CCM (EF
35%-45%), the risk involved in performing such a clinical investigation seems
acceptable.
Study objective
The study is designed to substantiate the efficacy of CCM in the heart failure
population with ejection fraction ranging between 25 and 45%. The study is
designed in an adaptive manner to ensure proper statistical significance and
power of the primary efficacy evaluation.
Study design
The study is a prospective, multi-center, randomized study comparing CCM plus
optimal medical therapy (OMT) (Treatment Group) to OMT alone (Control Group)
over a 6 month period.
The total number of patients enrolled and randomized at up to about 20 sites
will be 100 (50 in the treatment group and 50 in the control group). The number
of patients may be adjusted to no more than 200, after interim analysis of V02
data from about 50 cases.
Intervention
Subjects undergoing implantation of an OPTIMIZER pulse generator and associated
leads will be prepared for device implantation according to the procedure of
the institution. After access to the subclavian or cephalic vein, an atrial
lead will be placed transvenously into the right atrium for sensing atrial
activity. Two additional leads will be placed transvenously into the right
ventricle for sensing ventricular activity and delivering CCM signals. The
preferred lead arrangement is for one RV lead to be placed in the anterior
septal groove and the other in the posterior groove approximately half way
between the base and apex. The second most preferred lead arrangement would be
for both leads to be positioned in the anterior or posterior septal groove with
a Separation of at least ~2 cm.
Study burden and risks
Potential risks associated with heart failure and interventional cardiac
procedures:
The results of clinical studies suggest that there are no significant risks to
subjects directly related to application of CCM signals. However, there are
recognized risks associated with the heart failure state itself, with
interventional cardiac procedures in heart failure patients and potentially
with the use of the OPTIMIZER System. These risks are described in section 3
(page 14-17) of the study protocol.
As a result of participation in the study, patients are asked to perform two
standard cardiopulmonary stress tests each at baseline and at 24 weeks. The
cardiopulmonary stress test is non-invasive, typically only lasts about 10
minutes and is widely used in clinical practice and in heart failure research.
Therefore, while the performance of 4 tests in 6 month is typically more than
routinely done in standard practice, it presents minimal risk to patients.
The therapy is provided by a CE marked device, and has been demonstrated to be
safe while providing clinical benefit to the patient. The potential risks are
balanced by the potential benefits which significantly outweigh any potential
negative consequences that could still arise, despite the mitigations applied
Breitwiesenstr. 19
Stuittgart 70565
DE
Breitwiesenstr. 19
Stuittgart 70565
DE
Listed location countries
Age
Inclusion criteria
a) Baseline ejection fraction * 25% and *45% (as assessed by the site)
b) NYHA class II or III despite receiving optimal medical therapy for heart failure, stable for at least 30 days based on patient*s medical records (chronic, not transient, heart failure)
c) Baseline VO2,max * 9 and * 18.5 ml O2/Kg/min
Exclusion criteria
a) Potentially correctible cause of HF (valvular, congenital, or untreated ischemic heart disease)
b) Clinically significant angina pectoris
c) Hospitalization for HF requiring the use of inotropic support within 30 days of enrollment
d) PR interval greater than 375 ms
e) Permanent or long-standing persistent atrial fibrillation/flutter, or cardioversion within 30 days of enrollment.
f) Exercise tolerance limited by condition other than heart failure (e.g., angina, COPD, peripheral vascular disease, orthopedic or rheumatologic conditions) or unable to perform baseline stress testing
g) Scheduled for a CABG or a PTCA procedure, or CABG procedure within 90 days or a PTCA procedure within 30 days of enrollment.
h) Biventricular pacing system, or indication for Biventricular pacing system
i) Myocardial infarction within 90 days of enrollment.
j) Mechanical tricuspid or aortic valves.
k) Ventricular assist device
l) Prior heart transplant
m) Pregnant or planning to become pregnant during the study
n) Age below 18
o) Subject participating in another study, unrelated to CCM, at the same time (or within 30 days prior to enrollment to this study)
p) Subjects on dialysis
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 |
|---|---|
| CCMO | NL53739.058.15 |