The objective of this clinical study is to assess the safety and effectiveness of the Apollo Intravascular Lithotripsy (IVL) System for lithotripsy-enhanced balloon dilatation of calcified, stenotic de novo coronary lesions prior to stenting.The…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety:
The primary safety endpoint is freedom from major adverse cardiac events (MACE)
within 30 days following the index procedure. MACE is defined as the occurrence
of cardiac death, MI or TVR.
• Myocardial Infarction (MI) is defined as CK-MB level > 3 times the upper
limit of lab normal (ULN) value with or without new pathologic Q wave 12 to 24
hours post procedure or at discharge (periprocedural MI) and by the Fourth
Universal Definition of Myocardial Infarction beyond discharge (spontaneous MI)
• Target Vessel Revascularization (TVR) is defined as revascularization at the
target vessel (including the target lesion) after completion of the index
procedure.
Effectiveness:
The primary effectiveness endpoint is the rate of procedural success defined as
successful stent delivery with a residual stenosis <50% (angiographic core
laboratory assessed) and freedom from in-hospital MACE.
Secondary outcome
The secondary endpoints are:
1. Device crossing success defined as the ability to deliver the IVL catheter
across the target lesion and delivery of lithotripsy without serious
angiographic complications immediately after IVL.
2. Angiographic success defined as stent delivery with < 50% residual stenosis
and without serious angiographic complications.
3. Procedural success defined as stent delivery with a residual stenosis <= 30%
(core laboratory assessed) and without in-hospital MACE.
4. Angiographic success defined as stent delivery with <=30% residual stenosis
and without serious angiographic complications.
5. Serious angiographic complications defined as severe dissection (Type D to
F), perforation, abrupt closure, and persistent slow flow or persistent no
reflow.
6. MACE within 6 months.
7. Target lesion failure (TLF) defined as cardiac death, target vessel MI (Q
wave and non-Q wave), or ischemia-driven target lesion revascularization
(ID-TLR) by percutaneous or surgical methods at 30 days and 6 months.
8. At each time period: All deaths, cardiac deaths, MIs, TV-MIs, procedural and
nonprocedural MIs, ID-TVRs, ID-TLRs, non-ID-TLRs, non-ID-TVRs, all
revascularizations (ID and non-ID), and stent thrombosis (Academic Research
Consortium (ARC) definite, probable, definite or probable).
9. Sensitivity analyses will be reported for MI using the Fourth Universal
Definition of MI and the Society for Cardiovascular Angiography and
Interventions (SCAI) definitions at 30 days and 6 months.
Background summary
Coronary artery disease (CAD) is caused by atherosclerosis within the coronary
arteries which results in arterial narrowing and restricted blood flow to the
heart. This can lead to symptoms of angina and decreased heart function. CAD is
the most common form of heart disease and the leading cause of death in the
United States (Braun, 2018). Although the mortality for this condition has
gradually declined in western countries, it still causes about one-third of all
deaths in people older than 35 years (Nichols 2014).
Patients with symptomatic CAD typically fall into one of two subtypes, those
with stable ischemic heart disease (SIHD) and those with acute coronary
syndromes (ACS). SIHD results from slow growing plaques that over time narrow
the coronary artery until ischemia and symptoms develop. Non-invasive testing
such as stress tests or cardiac CT scans are helpful in diagnosing this
condition. Anti-anginal medications are the initial treatment of choice for
these patients, however those with ongoing symptoms can derive significant
benefit from revascularization (Bangalore, 2020). Patients with ACS have
unstable atherosclerotic plaques that fissure or rupture and acutely or
partially obstruct a coronary artery. These patient*s symptoms usually do not
resolve with medications alone and require urgent revascularization.
Current Treatments options are:
- Pharmacotherapy: Antiplatelets (e.g., aspirin, P2Y12 inhibitors),
antianginals (e.g., beta-blockers, nitrates, calcium channel blockers), lipid
control (e.g., statins, non-statin LDL lowering treatments, non-LDL therapies),
glycemic control.
- Coronary Bypass grafting (CABG): Currently indicated for patients with
complex 3-vessel coronary artery disease involving the proximal left anterior
descending artery (LAD) and/or left main coronary artery (LM). Depending on the
complexity of disease, when compared to percutaneous coronary intervention in
the SYNTAX trial, CABG is associated with a decrease need for repeat
revascularization and similar to improved periprocedural morbidity and
mortality, at the expense of a longer initial hospitalization. For patients who
are not surgical candidates due to multiple comorbid conditions, PCI and
medical therapy remain the only therapeutic options.
- Transcatheter Coronary interventions:
• Percutaneous transluminal anioplasty (PTA): first performed in 1977, it was
one of the first treatment options for CAD and is associated with low
complication rates. Isolated balloon angioplasty is no longer the treatment of
choice as it is plagued by high rate of failure resulting from restenosis and
vascular recoil.
• Cutting and scoring balloons special balloons that contain microsurgical
blades bonded to its* surface with the intention of scoring/cutting into
atherosclerotic plaque.
• Drug-coated balloons (DCB) delivers antiproliferative drugs to local arterial
tissue and reduces risk of restenosis (Picard, 2017).
• Atherectomy - a minimally invasive endovascular surgery technique to remove
or debulk atherosclerotic plaque from diseased arteries.
• Lithotripsy (IVL): lithotripsy has been around since the early 1980s, and
used to break down stones in the kidney, gallbladder, or ureter with sound
waves. Since then, the procedure has been adapted for intravascular calcium
modification using sonic pressure waves to modify intimal and medial calcium.
• Cryoplasty: uses nitrous oxide to optimize the dilation effects of standard
angioplasty by delivering cryothermal energy to the atherosclerotic plaque.
• Stents: routine implantation of stents has improved the clinical course after
balloon angioplasty and is now standard in the treatment of stenosis of native
coronary arteries and venous bypass vessels (Ruß, 2009).
The study involves the evaluation of a new medical device (Apollo IVL system)
which uses a combination of Lithotripsy (IVL) with a low pressure balloon to
break the plague and widen the affected artery.
Study objective
The objective of this clinical study is to assess the safety and effectiveness
of the Apollo Intravascular Lithotripsy (IVL) System for lithotripsy-enhanced
balloon dilatation of calcified, stenotic de novo coronary lesions prior to
stenting.
The data is used for obtaining market access.
Study design
The RESTORE CAD study is a pre-market prospective, non- randomized, multicenter
study to obtain data for support of market access.
The follow-up period is 6 months.
The tests performed within the study are standard of care, limiting the risk of
participating in the study for the patients.
A total of 60 subjects is planned, exclusive of roll-in subjects for primary
analysis. In addition to the primary analysis sample size, up to a maximum of
twenty (20) roll-in subjects will be allowed.
Intervention
The study procedure consists of standard percutaneous coronary interventional
(PCI) techniques, including access site preparation, introduction of the
catheter portion of the device, inflation and deflation of the balloon,
withdrawal of the catheter, stent implantation, and access site closure.
PCI is performed via either femoral or radial access with a minimum 6F guiding
catheter. The IVL catheter is passed across the lesion over a standard 0.014*
guidewire. If the IVL catheter will not cross the lesion, adjunctive tools
(buddy wire, balloon predilatation, or guide catheter extension) can be used at
operator discretion before reinsertion of the IVL catheter. Atherectomy or
cutting/scoring balloons is not permitted.
Once the balloon is placed in the target lesion area, the balloon is inflated
to 4 ATM and a treatment cycle is activated by pressing and holding the
treatment activation button, leading to delivery of pulsatile acoustic
(shockwaves) for up to the defined number of pulses per treatment cycle.
A different diameter IVL balloon may be used if significant vessel tapering
occurs in the target lesion.
The number of IVL catheters used is dependent on lesion length, vessel diameter
of the treated segments, and total number of pulses required to effectively
treat the target lesion.
Study burden and risks
Potential risks associated with the Apollo Intravascular Lithotripsy System can
be associated with device use, general anesthesia, catheterization and
diagnostic imaging for subjects with CAD.
The potential risks and discomforts associated specifically with treating CAD
with the Apollo IVL System are expected to be similar to the risks associated
with the use of other commercially available, standard of care devices.
Potential risks/adverse events associated with the Apollo IVL system, general
anesthesia, catheterization and diagnostic imaging for subjects with CAD ,as
reported in the published literature, are outlined below.
Risks/adverse events may be local or systemic in nature and vary from minor
reactions to major reactions that may be life-threatening or result in death.
Documented risks associated with standard catheter-based cardiac
interventions/procedures are reported in the published literature and include,
but are not limited to, the following:
• Abrupt vessel closure
• Allergic reaction to contrast medium, anticoagulant and/or antithrombotic
therapy
• Aneurysm
• Arrhythmia
• Arteriovenous fistula
• Bleeding complications
• Cardiac tamponade or pericardial effusion
• Cardiopulmonary arrest
• Cerebrovascular accident (CVA)
• Coronary artery/vessel occlusion, perforation, rupture or dissection
• Coronary artery spasm
• Death
• Emboli (air, tissue, thrombus or atherosclerotic emboli)
• Emergency or non-emergency coronary artery bypass surgery
• Emergency or non-emergency percutaneous coronary intervention
• Entry site complications
• Fracture of the guide wire or failure/malfunction of any component of the
device that may or may not lead to device embolism, dissection, serious injury
or surgical intervention
• Hematoma at the vascular access site(s)
• Hemorrhage
• Hypertension/ Hypotension
• Infection/sepsis/fever
• Myocardial Infarction
• Myocardial Ischemia or unstable angina
• Pain
• Peripheral Ischemia
• Pseudoaneurysm
• Renal failure/insufficiency
• Restenosis of the treated coronary artery leading to revascularization
• Shock/pulmonary edema
• Slow flow, no reflow, or abrupt closure of coronary artery
• Stroke
• Thrombus
• Vessel closure, abrupt
• Vessel injury requiring surgical repair
• Vessel dissection, perforation, rupture, or spasm
In addition, patients may be exposed to other risks associated with coronary
interventional procedures, including risks from conscious sedation and local
anesthetic, the radiographic contrast agents used during angiography, the drugs
given to manage the subject during the procedure, and the radiation exposure
from fluoroscopy.
Risks identified as related to the device and its use:
• Allergic/immunologic reaction to the catheter material(s) or coating
• Device malfunction, failure, or balloon loss of pressure leading to device
embolism, dissection, serious injury or surgical intervention
• Atrial or ventricular extrasystole
• Atrial or ventricular capture
Potential Benefits:
Potential benefits to the subjects participating in this study may include but
are not limited to: no surgical incision - faster recovery, less pain, reduced
hospital stay, and reduced complications.
Avenida Encinas 5993
Carlsbad CA 92008
US
Avenida Encinas 5993
Carlsbad CA 92008
US
Listed location countries
Age
Inclusion criteria
1. Age of subject is >=18.
2. Subjects with native coronary artery disease (including stable or unstable
angina, or silent
ischemia) suitable for PCI
3. For patients with unstable ischemic heart disease, biomarkers (troponin or
CK-MB) must be less
than or equal to the upper limit of lab normal within 12 hours prior to the
procedure (note: if
both labs are drawn, both must be normal).
4. For patients with stable ischemic heart disease, biomarkers may be drawn
prior to the index
procedure or at the time of the procedure from the side port of the sheath.
o If drawn prior to the procedure, biomarkers (troponin or CK-MB) must be less
than or equal
to the upper limit of lab normal within 12 hours of the procedure (note: if
both labs are
drawn, both must be normal).
o If biomarkers are drawn at the time of the procedure from the side port of
the sheath prior to
any intervention, results do not need to be analyzed prior to enrollment (note:
CK-MB is
required if drawn from the sheath).
5. Left ventricular ejection fraction (LVEF) >25% within 6 months (note: in the
case of multiple
assessments of LVEF, the measurement closest to enrollment will be used for
this criterion; may
be assessed at time of index procedure)
6. Subject or legally authorized representative, signs a written Informed
Consent form to
participate in the study, prior to any study-mandated procedures
7. Lesions in non-target vessels requiring PCI may be treated either:
o >30 days prior to the study procedure if the procedure was unsuccessful or
complicated; or
o >24 hours prior to the study procedure if the procedure was successful and
without
complications (defined as a final lesion angiographic diameter stenosis <30%
and TIMI 3
flow (visually assessed) for all non-target lesions and vessels without
perforation, cardiac
arrest or need for defibrillation or cardioversion or hypotension/heart failure
requiring
mechanical or intravenous hemodynamic support or intubation, and with no
post-procedure
biomarker elevation >normal); or
o >30 days after the study procedure
Angiographic Inclusion Criteria
1. The target lesion must be a de novo coronary lesion that has not been
previously treated with any
interventional procedure
2. Single de novo target lesion stenosis of protected LMCA, or LAD, RCA or LCX
(or of their
branches) with:
o Stenosis of >70% and o Stenosis >50% and <70% (visually assessed) with evidence of ischemia via
positive stress
test, or fractional flow reserve value < 0.80, or iFR <0.90 or IVUS or OCT
minimum lumen
area < 4.0 mm2
3. The target vessel reference diameter must be > 2.5 mm and < 4.0 mm
4. The lesion length must not exceed 40 mm
5. The target vessel must have TIMI flow 3 at baseline (visually assessed; may
be assessed after
pre-dilatation)
6. Evidence of calcification at the lesion site by, a) angiography, with
fluoroscopic radio-opacities
noted without cardiac motion prior to contrast injection involving both sides
of the arterial wall
in at least one location and total length of calcium of at least 15 mm and
extending partially into
the target lesion, OR by b) IVUS or OCT, with presence of > 270 degrees of
calcium on at least
1 cross section
7. Ability to pass a 0.014* guide wire across the lesion
Exclusion criteria
1. Any comorbidity or condition which may reduce compliance with the protocol,
including follow-up visits
2. Subject is a member of a vulnerable population as defined in 21 CFR 56.111,
including
individuals with mental disability, persons in nursing homes, children,
impoverished persons,
persons in emergency situations, homeless persons, nomads, refugees, and those
incapable of
giving informed consent. Vulnerable populations also may include members of a
group with a hierarchical structure such as university students, subordinate
hospital and laboratory personnel,
employees of the Sponsor, members of the armed forces, and persons kept in
detention
3. Subject is participating in another research study involving an
investigational agent
(pharmaceutical, biologic, or medical device) that has not reached the primary
endpoint
4. Subject is pregnant or nursing (a negative pregnancy test is required for
women of child-bearing
potential within 7 days prior to enrollment)
5. Unable to tolerate dual antiplatelet therapy (i.e., aspirin, and either
clopidogrel, prasugrel, or
ticagrelor) for at least 6 months (for patients not on oral anticoagulation)
6. Subject has an allergy to imaging contrast media which cannot be adequately
pre-medicated
7. Subject experienced an acute MI (STEMI or non-STEMI) within 30 days prior to
index
procedure, defined as a clinical syndrome consistent with an acute coronary
syndrome with
troponin or CK-MB greater than 1 times the local laboratory*s upper limit of
normal
8. New York Heart Association (NYHA) class III or IV heart failure at time of
index procedure
9. Renal failure with serum creatinine >2.5 mg/dL, GFR <40 or chronic dialysis
10. History of a stroke or transient ischemic attack (TIA) within 6 months, or
any prior intracranial
hemorrhage or permanent neurologic deficit
11. Active peptic ulcer or upper gastrointestinal (GI) bleeding within 6 months
12. Untreated pre-procedural hemoglobin <10 g/dL or intention to refuse blood
transfusions if one
should become necessary
13. Coagulopathy, including but not limited to platelet count <100,000 or
international normalized
ratio (INR) >1.7 (INR is only required in subjects who have taken warfarin
within 2 weeks of
enrollment)
14. Subject has a hypercoagulable disorder such as polycythemia vera, platelet
count >750,000 or
other disorders
15. Uncontrolled diabetes defined as a HbA1c > l0%
16. Subject has an active systemic infection on the day of the index procedure
with either fever,
leukocytosis or requiring intravenous antibiotics
17. Subjects in cardiogenic shock
18. Uncontrolled severe hypertension (systolic BP >180 mm Hg or diastolic BP
>110 mm Hg)
19. Subjects with a life expectancy of less than 1 year
20. Non-coronary interventional or surgical structural heart procedures (e.g.,
TAVR, MitraClip,
LAA or PFO occlusion, etc.) within 30 days prior to the index procedure
21. Planned non-coronary interventional or surgical structural heart procedures
(e.g., TAVR,
MitraClip, LAA or PFO occlusion, etc.) within 30 days after the index procedure
22. Subject refusing or not a candidate for emergency coronary artery bypass
grafting (CABG)
surgery
23. Planned use of atherectomy, scoring or cutting balloon, Shockwave
lithotripsy device or any
investigational device other than the study device
24. High SYNTAX Score (> 33) if assessed as standard of care, unless the local
heart team has met
and recommends PCI is the most appropriate treatment for the patient
25. Unprotected left main diameter stenosis >30%
26. Target vessel is excessively tortuous defined as the presence of two or
more bends >90º or three
or more bends >75º
27. Definite or possible thrombus (by angiography or intravascular imaging) in
the target vessel
28. Evidence of aneurysm in target vessel within 10 mm of the target lesion
29. Target lesion is an ostial location (LAD, LCX, or RCA, within 5 mm of
ostium) or an
unprotected left main lesion
30. Target lesion is a bifurcation involving a side branch of 2.5mm or more
with ostial diameter
stenosis >=50%, and intention to treat the side branch with balloon and/or stent
31. Second lesion with >50% stenosis in the same target vessel as the target
lesion including its side
branches
32. Target lesion is located in a native vessel that can only be reached by
going through a saphenous
vein or arterial bypass graft
33. Previous stent within the target vessel implanted within the last year
34. Previous stent within 10 mm of the target lesion regardless of the timing
of its implantation
35. Angiographic evidence of a dissection in the target vessel at baseline or
after guidewire passage
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 | NL81513.000.22 |