Since published rates of PPMI are limited in patients treated with RA and IVL, this study is designed as a pilot study in order to measure PPMI in patients treated with RA and IVL. At the same time a comparison will be carried out between the two…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome: difference in the rate of peri-procedural myocardial
infarction (Type 4a of the universal Definition of Myocardial Infarction) in
patients allocated to Shockwave IVL group versus RA group.
Secondary outcome
Secondary outcomes: in centres where the index of microcirculatory resistance
(IMR) can be measured before and after PCI, a rate of peri-procedural
microvascular dysfunction will be measured. Other secondary outcomes:
peri-procedural myocardial injury (defined as a peak high sensitivity troponin
T of >=0.014ng/mL); descriptive study of IMR measurements in calcified lesions;
technical success (defined as a residual stenosis <30% in the presence of TIMI
III flow); procedural success (defined as technical success with no in-hospital
MACE); in cases where intra-coronary imaging such as OCT is performed:
interaction between calcium score and primary endpoint; comparison of stent
expansion between the two groups; procedure cost; procedure duration; radiation
dose; cross-over to alternative strategy; 30-day and 1-year MACE.
Background summary
Percutaneous coronary intervention (PCI) is intended to relieve myocardial
ischemia by improving blood flow in the epicardial coronary arteries, thereby
relieving angina pectoris and improving outcomes in patients with coronary
artery disease (CAD).1 However, the efficacy of PCI may be compromised by
incidental microvascular obstruction and peri-procedural myocardial infarction
(PPMI), which occurs in about 10-15% of cases and is associated with an
increase in the rate of major adverse cardiovascular events (MACE).2 One
meta-analysis, including 20 studies and 15*581 patients with stable angina
undergoing elective PCI, demonstrated that overall troponin was raised in more
than 30% of patients after an elective PCI. Any troponin elevation was
associated with a significantly increased mortality risk (4.4% vs 3.3%,
p=0.001; OR=1.35, 95% CI 1.13 to 1.60).3 Another meta-analysis used an earlier
universal definition of PPMI (Type 4a)4 with a troponin elevation of 3 times
the URL as the cut-off point.5 It included 7578 patients from 15 studies of
patients undergoing non-emergency PCI with normal baseline troponin levels.
Troponin elevation occurred in 28.7% of the procedures and the incidence of
Type 4a MI was 14.5%. In keeping with previous data, Type 4a MI increased the
risk of MACE compared with those patients without troponin elevation at an
average follow-up of about 17.7 months (OR=2.25, 95% CI 1.26 to 4.00, p=0.006).
Patients with elevation of troponin less than 3 times the URL did not have a
worse prognosis during follow-up (OR=1.85, 95% CI 0.80 to 4.28, p=0.15).5
The mechanism of PPMI is thought to be related to side branch occlusion,
coronary artery dissection and acute microvascular damage caused by
embolization of plaque debris during the PCI (Figure 2).6,7 Recent data
demonstrates a close relationship between peri-procedural myocardial injury or
Type 4a PPMI and microvascular dysfunction.8 Microvascular dysfunction,
measured with the index of microcirculatory resistance (IMR) significantly
increased after elective PCI in patients with stable coronary artery disease,
and was significantly associated with myocardial injury and Type 4a PPMI.
The expanding aged population has led to an increase in the frequency of
calcified CAD. Moderate and severe calcified coronary lesions are particularly
challenging for the interventional cardiologist since these lesions impede the
delivery of intra-coronary devices and increase the risk of stent
under-expansion with consequent adverse procedural and clinical outcomes.9
Coronary artery calcification is associated with more frequent peri-procedural
myocardial infarction.2,10 To overcome these challenges several devices
including non-compliant balloons (including very high-pressure balloons),
scoring devices, cutting devices, rotational and orbital atherectomy and
excimer laser coronary angioplasty are available to the interventional
cardiologist.11 The Shockwave coronary intravascular lithotripsy (IVL) catheter
balloon catheter (Shockwave Medical, Santa Clara, CA) is a single-use sterile
disposable catheter that contains multiple lithotripsy emitters enclosed in an
integrated balloon.12 It emits sonic pressure waves in a circumferential field
causing the selective fracture of calcium, altering vessel compliance and
permitting further expansion of the vessel wall. This provides a potentially
safer alternative to other calcium-modifying devices since there is a low risk
of dissection and perforation.13 Furthermore, it is proposed,12 but not yet
tested, that this IVL device reduces the risk of atheromatous embolization,
which would reduce the risk of peri-procedural myocardial infarction and
microvascular dysfunction. Theoretically, the use of IVL, instead of other
devices such as rotational atherectomy (RA), could reduce peri-procedural
complications, periprocedural myocardial infarction and microvascular
dysfunction, and thus, improve the prognosis for patients with moderately and
severely calcified lesions.14
Study objective
Since published rates of PPMI are limited in patients treated with RA and IVL,
this study is designed as a pilot study in order to measure PPMI in patients
treated with RA and IVL. At the same time a comparison will be carried out
between the two treatment options.
The null hypothesis is that there is no difference in peri-procedural
myocardial infarction (Type 4a of the universal Definition of Myocardial
Infarction) or microvascular dysfunction in patients treated with IVL or RA.
Primary outcome: difference in the rate of peri-procedural myocardial
infarction (Type 4a of the universal Definition of Myocardial Infarction) in
patients allocated to Shockwave IVL group versus RA group.
Secondary outcomes: in centres where the index of microcirculatory resistance
(IMR) can be measured before and after PCI, a rate of peri-procedural
microvascular dysfunction will be measured. Other secondary outcomes:
peri-procedural myocardial injury (defined as a peak high sensitivity troponin
T of >=0.014ng/mL); descriptive study of IMR measurements in calcified lesions;
technical success (defined as a residual stenosis <30% in the presence of TIMI
III flow); procedural success (defined as technical success with no in-hospital
MACE); in cases where intra-coronary imaging such as OCT is performed:
interaction between calcium score and primary endpoint; comparison of stent
expansion between the two groups; procedure cost; procedure duration; radiation
dose; cross-over to alternative strategy; 30-day and 1-year MACE.
Study design
In this multicentre, prospective, randomized-controlled open label study we
will measure rates of peri-procedural myocardial infarction and changes in
microvascular function after PCI in 170 patients (85 per arm) treated with
Shockwave intravascular lithotripsy (IVL) versus RA. Patients with moderately
and/or severely calcified coronary lesions, with the expected need of plaque
modification, which are equally suitable for IVL and RA and on the condition
that with or without low profile balloon (<= 1.5 mm) preparation, a >= 2.5
non-compliant balloon can cross the lesion, will be recruited according to the
scheme in Figure 1. The calcified lesion must be suitable for both IVL and RA
as defined in Figure 1 and the operator believes that either IVL or RA could be
used. The primary outcome will be difference in the rate of peri-procedural
myocardial infarction (Type 4a of the universal Definition of Myocardial
Infarction). Peri-procedural myocardial injury and infarction will be defined
by an increase in high-sensitivity Troponin T according to the Fourth Universal
Definition of Myocardial Infarction,15 while microvascular dysfunction will be
defined by an Index of Microcirculatory Resistance (IMR) of >=25.16 Patients
will undergo study-related clinical follow up at 30 days and 12 months.
Intervention
- Shockwave ballon
- Rotablatie
Study burden and risks
Minor complaints due to extra blood samples at 8 and 16hr post PCI.
Herestraat 49
Leuven 3000
BE
Herestraat 49
Leuven 3000
BE
Listed location countries
Age
Inclusion criteria
Patient older than 18 years.
The subject has stable or unstable angina pectoris, or a positive functional
study for ischemia.
The subject is eligible for PCI.
The subject gives consent prior to study inclusion.
The subject has a moderate to severe calcified lesion with the expected need of
plaque modification, on the condition that with or without low profile balloon
(<= 1.5 mm) preparation, a >= 2.5 non-compliant balloon can cross the lesion.
The calcified lesion has a 50-90% diameter stenosis by angiographic assessment.
Exclusion criteria
Previous and/or planned brachytherapy of target vessel.
Pregnant and/or breast-feeding females or females who intend to become pregnant.
Patients who intend to have a major surgical intervention within 6 months of
enrolment in the study.
Patients who previously participated in this study.
Subject has experienced an acute myocardial infarction 72 hours prior to the
index procedure, as defined either by the presence of a new Q-wave in 2 or more
contiguous leads, or by a CK greater than two times site upper reference limit
(URL) with presence of CK-MB greater than the site URL.
The subject has suffered a stroke or transient ischemic neurological attack or
cerebrovascular accident within the past six months, or has any known
intracranial mass, arteriovenous malformation, aneurysm or other intracranial
pathology.
The subject has experienced a significant gastrointestinal or genitourinary
bleed within the past six months, or has had any active bleeding within two
months.
Planned revascularization of target vessel within 1 year after index procedure.
Lesions not ideal for Shockwave treatment:
Longer than 40mm.
The target vessel contains intraluminal thrombus.
The subject has had a prior stent in the target lesion, including a 5mm zone
proximal and distal to the lesion.
Design
Recruitment
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 | NCT05208749 |
| CCMO | NL81701.078.22 |