The objective of this study is to assess the safety and effectiveness of the WISE System (providing LV pacing) when used in conjunction with a co-implanted system (ICD, pacemaker, CRT-P, or CRT-D) for bi-ventricular (BiV) pacing for CRT in heart…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Safety
Freedom from Type 1 Complications through 6M compared to a performance goal of
70% for all enrolled in Part II Randomized + Part III Single-arm subjects.
Primary Efficacy 1
Mean relative (%) change in LVESV from baseline to 6 months in PU-HRU subjects
with WiSE CRT system switched ON after implantation compared to a performance
goal of - 9.3 %.
The primary efficacy endpoint analysis will be done in PU-HRU Treatment arm
subjects from Part II Randomized and Part III Single-arm subjects.
Secondary outcome
Secondary Efficacy 1
Electrode Acoustic Pacing Capture Threshold (APCT) measured at the 6-month
follow-up post-implant visit (in the Treatment arm).
Secondary Efficacy 2
Electrode Acoustic Pacing Capture Threshold Stability (APCT Stability) measured
from predischarge through the 6-month follow-up post-implant visit
Ancillary
LVESV Distribution Shift, defined as the percentage of subjects with an
improvement of greater than 15% in LVESV, from baseline through 6 months.
The mean change in NT-proBNP from baseline, compared between arms (baseline to
6 months.)
The mean change in intrinsic QRS duration, compared between arms (baseline to 6
months).
The percent subjects with at least a one class improvement in NYHA. (baseline
to 6 months).
Background summary
Standard application of CRT, or biventricular pacing (BiV), involves the
placement of a right ventricular (RV) lead for pacing the right ventricle and a
coronary sinus (CS) lead in an epicardial coronary vein to provide LV pacing.
CRT is a recognized device therapy for heart failure that has been studied
extensively for over 20 years, leading to a large body of knowledge supporting
the therapy and elucidating its challenges and limitations. CRT is currently
the standard of care in patients who have LV dysfunction, mild to severe heart
failure, symptoms despite optimal medical therapy, and QRS prolongation. CRT
is currently recommended for use by the ACC/AHA/HRS guidelines (Epstein 2012)
for a number of subsets of heart failure patients based on evidence from large
scale randomized trials.
Patients who do not respond clinically to CRT (non-responders) have been
reported in the range of ~ 30% (Abraham 2002, McAlister 2007, Foley 2009). A
review of observational studies of CRT has shown non-responders ranged from 18
to 45 percent with a variety of definitions of non-response (Foley 2009).
Another group of patients, described here as previously untreatable, exist
because of failed LV lead implants or other LV lead issues (high thresholds,
phrenic nerve stimulation, and dislodgement) that result in inability to
provide CRT therapy. Due to the varied anatomy of the CS vasculature and
difficulty with access preventing LV lead placement, some patients are not able
to receive CRT. Failed implants due to lead placement in the CS are high, with
reported rates in the ~ 5-10% range (Leon 2005). Unsuccessful LV lead
placement in the MIRACLE study was shown to be 7.6%, 5% in CARE-HF, and 13% for
CRT-P and 9% for CRT-D in COMPANION (Matsumoto 2007). Additionally, a
substantial rate of perioperative and postoperative complications also exist (~
5-10%) (Leon 2005, Linde 2008).
Additionally, there is a group of patients who are considered high-risk
upgrades (HRU) in whom standard CRT upgrade is not advisable due to known
relative contraindications to CS lead implant.
The WiSE System is designed to provide leadless pacing on the LV endocardium as
well as patient specific selection of the LV pacing site location. The system
(in conjunction with a co-implanted device, i.e. pacemaker or defibrillator) is
comprised of a wireless endocardial LV electrode that is inserted
transarterially or transvenously, allowing for placement throughout the LV as
compared to the limited choices afforded by the coronary veins. The electrode
is powered wirelessly using ultrasound delivered by a subcutaneously implanted
transmitter. This approach potentially resolves many of the issues associated
with current methods of CRT. It has been designed to provide endocardial pacing
without the stroke and TIA risks of placing a standard pacing lead inside the
LV. It allows for LV stimulation at a pacing site of choice rather than only
locations dictated by the coronary venous anatomy. It avoids using the coronary
venous system on the epicardial aspect of the LV for lead implant, thereby
potentially eliminating access, placement, perforation, occlusion, infection,
phrenic nerve and pacing threshold issues.
EBR Systems seeks to study the safety and effectiveness of the WiSE System as
an alternative to current methods of LV pacing in CRT. A large unmet clinical
need exists in patients who have not responded to conventional CRT or who are
defined as previously untreatable due to LV lead related issues. It is expected
that LV endocardial pacing as well as selection of an LV pacing site specific
to the patient may improve the outcome in these patients.
Study objective
The objective of this study is to assess the safety and effectiveness of the
WISE System (providing LV pacing) when used in conjunction with a co-implanted
system (ICD, pacemaker, CRT-P, or CRT-D) for bi-ventricular (BiV) pacing for
CRT in heart failure patients.
Study design
This study is a prospective clinical trial which is comprised of three seperate
multi-center, multicountry parts:
Part I Roll-in, single-arm, open label
Part II Randomized, two-arm, randomized 1:1, double blind
Part III Single-arm, singele-arm, open label
Subjects will be considered enrolled after they consent, pass the study
inclusion and exclusion criteria and undergo anesthesia/sedation for implant
of the WiSE CRT system.
For Part II Randomized subjects only, after successful implant, the WiSE CRT
system will be programmed to OFF until randomization. The subjects in the
randomization cohort will be assigned to either the Treatment or Control Arms,
employing a 1:1 randomization to the Treatment Arm (WiSE ON) and Control Arm
(WiSE OFF).
Part I , Roll-in subjects and Part III, Single-arm subjects will be programmed
to WiSE ON following the procedure and followed similarly to subjects in the
Treatment Arm.
Patients will undergo scheduled evaluations at pre-implant,
pre-discharge/randomization, 1 month (window to cover wound check period +/-21
day), 3 months, 6 months and every 6 months post implantation until the 24
month follow-up.Hereafter patients will be checked year 3, year 4 and year 5.
Endpoints will be evaluated through 6 months. After their 6 months evaluation
patients in the Part II Control Arm will be programmed to WiSE ON.
Intervention
implantation of a WiSE System. The system will be programmed ON in the active
group at discharge. The system wll be programmed OFF at discharge in the
control group. In the last group the system will be programmed ON at 6 months.
Study burden and risks
As with any medical procedure or implantable device, the study device
implantation procedure and the implanted device carry potential risks and
potential benefits. In addition to the known potential risks described below,
the device may pose additional potential risks, the nature of which are unknown.
Participation in this study may benefit enrolled patients by providing CRT to
those previously unable to receive a CRT or providing another opportunity to
those who currently are not responding to CRT. The participating patients may
receive improved delivery of CRT and the resultant benefits of improved cardiac
function. In addition, the clinical data obtained from this study may benefit
other patients with CHF requiring CRT in the future.
Risks related to the implantation procedure
Potential risks related to the implantation procedure include but are not
limited to:
• Access site and pocket complications (e.g. pain, bruising, bleeding,
infection)
• Air embolism (air bubble in your blood stream)
• Air embolism, permanent injury or death due to air embolization and
infarction of distal organs
• Allergic reactions to sedatives, drugs, or other materials used during the
implant procedure
• Anemia
• Anesthesia related complications
• Aortic valve damage
• Arterial perforation, dissection, spasm
• Cardiac arrhythmias
• Cardiac tamponade
• Chronic nerve damage
• Death
• Device explant
• Dissection of the aorta or branch vessels (including femoral artery)
• Electrochemical burns
• Embolization of device or material, thrombus, or air to systemic circulation
increasing stroke and peripheral vascular occlusion risk, possible organ
damage, or death
• Esophagaeal bleeding(after TTE)
• Excessive bleeding
• Femoral artery complications
• Fever
• Hematoma at surgical incision, device pocket or arterial insertion site
(blood collected outside the vessel)
• Hemolysis
• Hypotension or hypertension (low or high blood pressure)
• Infection and/or sepsis
• Internal myocardial tissue damage, infract, hematoma
• Kidney injury due to imaging contrast use
• Migration of device implanted
• Mitral valve damage
• Myocardial infarction (heart attack)
• Myocardial tissue (heart muscle) injury or perforation
• Overexposure to x-ray fluoroscopic radiation
• Pain
• Pericardial effusion (fluid build-up around heart)
• Pneumothorax (collapsed lung)
• Pulmonary complications including embolism, respiratory failure and pneumonia
• Renal failure, possibly requiring dialysis
• Septal defect (if transseptal access is used for device implnat)
• Shock
• Sore throat (after TEE)
• Small risk of bleeding, heart attack or stroke (if intra-cardiac
echocardiography is done)
• Stroke or transient cerebrovascular events
• Thrombus formation/thromboembolism (blood clot)
WiSE System specific:
• Embolization/migration of the electrode or other delivery system material,
possible organ damage, death, or prolonged hospitalization*
Risks related to the post implant period
In addition to the known potential risks from the implant procedure, known post
implant risks of the WiSE System include many of the same risks associated with
the use of any commercially available CRT system as well as those unique to the
WiSE System which include but are not limited to:
• Breach of battery or battery connections
• Device migration
• Early battery depletion
• Electronic or mechanical component failure
• Excessive fibrotic growth
• Fluid accumulation in implant pockets
• Foreign body reaction (allergic reaction)
• Fracture or damage to the battery connection cable
• High rate or competitive ventricular pacing
• High rate ventricular pacing or inappropriate timed pacing that could lead to
arrhythmia or death
• Inadvertent device reprogramming
• Need for invasive procedure to correct system problem or effect
• No pacing therapy delivery or loss of pacing capture
• Pain
• Psychological disturbances (dependency, depression, fear of battery
depletion, fear of malfunction)
• Skin erosion over implanted device (device exposed through skin)
• Worsening heart failure
WiSE System specific
• Embolization/migration of device requiring surgical intervention, possible
organ damage, death, or prolonged hospitalization
• Inability to deliver therapy due to insufficient energy delivered to receiver
• Inappropriate synchronization/pacing (oversensing/undersensing), i.e
interference from external ultrasound sources
• Mechanical injury causing tissue damage
• Thermal tissue injury from transmitter elements
Potential Risks of the WiSE System
• Some components, e.g., residuals and/or extractables, of the devices may
accumulate at the lesion site and/or in downstream tissues and may cause an
adverse biological response. Preliminary animal data suggest this is not
occurring, but it is unclear whether the animal data will be directly
applicable to patients due to differences in metabolism.
• Some components of the devices contain titanium. Patients sensitive to
titanium or have a known titanium allergy should not use this
device.
Risks related to the study conduct
The risk increase for subject participating in the study might be related to
the new technology featured in the device and to procedures required in the
study. However it is expected that study participation may also benefit the
subjects due to the close scrutiny of their device function and rigorous
identification of adverse events.
Repeated follow-ups limit the risk of sub-optimal device setting. The
procedures and methods for data collection required by the protocol do not
differ significantly from routine CRT implantation and follow-up practice in
CRT subjects.
Use of the device not in conformance with this investigational plan and/or with
the Instructions for Use could introduce other issues.
480 Oakmead Parkway 480
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480 Oakmead Parkway 480
Sunnyvale CA 94085
US
Listed location countries
Age
Inclusion criteria
1. Patient with a class I or IIa (1) or (2) indication for implantation of a
CRT-D device according to current available guidelines (with additional QRS
criteria on Class IIa (1) and EF criteria minimum on all classes):
a. Class I: NYHA II, III, IV, EF <= 35%, LBBB, QRS>=150ms
b. Class IIa (1): NYHA II, III, IV, EF<=35%, LBBB, QRS>=130 to <150ms
c. Class IIa (2): NYHA II, III, IV, EF<=35%, non-LBBB, QRS>=150ms
2. Non-responder*: Patients who have a CRT system that is functional and
despite an adequate trial of Guideline Directed Medical Therapy (GDMT) and
attempts at optimal device programming the patient has not responded to therapy
for a minimum of 6 months. Non-response is defined as remailing clinically
unchanged or worsened:
a. EF has remained unchanged or worsened (defined as < 5% increase
since implant), and
b. The patient*s clinical status based in the totality of available clinical
evidence (such as NYHA
Class, exercise tolerance, QOL, or global assessment) has remained unchanged
or worsened, as
determined by the local Site Enrollment Committee (Site Enrollment Committee
is made up
of at least one electrophysiologist and a designated Heart Failure Specialist
(MD).
OR
*Previously Untreatable*: Patients who have a full or partial CRT system, who
meet general inclusion criteria and are deemed as *previously untreatable* for
one of the following reasons:
a. Patients in whom CS lead implantation for CRT has failed
b. CS lead implanted but has been programmed OFF
OR
. High risk upgrades:patients with relative contraindications to CS lead
implant
3. Patients on a stable GDMT
4. Patient must be 18 years old or over
5. Signed and dated informed consent
6. Patient has suitable anatomy for implant of the WiSE CRT System (e.g.
adequate
acoustic window, LV wall thickness in target implant area >= 5 mm, absence of LV
wall
structural abnormalities which may preclude implant)
Exclusion criteria
1. Pure RBBB
2. LVEDD >= 8cm
3. Non-ambulatory or unstable NYHA class IV
4. Contraindication to heparin, chronic anticoagulants or antiplatelet agents
5. Triple anticoagulant patients who cannot tolerate peri-procedural stopping of
anticoagulation therapy must be excluded
6. Patients with planned or expected lithotripsy treatment post-implant
7. Attempted device implant (pacemaker, ICD, CRT, LV lead) or successful
co-implant
within the prior 30 days
8. Life expectancy of < 12 months
9. Chronic hemodialysis
10. Stage 4 or 5 renal dysfunction defined as eGFR < 30
11. Grade 4 mitral valve regurgitation
12. Noncardiac implanted electrical stimulation therapy devices
13. Patients with a prosthetic aortic valve and a non-viable transseptal
approach for the electrode implant.
14. Patients with a prosthetic mitral valve and a non-viable transseptal
approach for the electrode implant
15. Unstable angina, acute MI, CABG, or PTCA within the past 1 month
16. Correctable valvular disease that is the primary cause of heart failure
17. Recent CVA or TIA (within the previous 3 months)
18. Patients with a history of paroxysmal or persistent atrial
fibrilation/flutter are excluded if they have had a documented
AF episode > 30 min or a cardioversion in the past 30 days from screening.
19. Patients with permanent AF are excluded if they have intact AV node
conduction (RV pacing >95%)
20. Already included in another clinical study that could confound the results
of this study
21. Pregnancy
22. Known drug or alcohol addiction or abuse
23. Moderate or severe aortic stenosis
24. Positive test for COVID-19 at screening
25. Subject unable to attend follow-up at the investigative center or unable,
for physical or
mental reasons, or to comply with the trial's procedures
26. For Part II randomized patients, those who will not tolerate being
randomized to the Control Group for 6 months
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 | NCT02922036 |
| CCMO | NL62355.075.17 |