To test whether immediate complete revascularization is non-inferior to staged (but within six weeks after index procedure) complete revascularization in ACS patients with multivessel disease
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoint is defined as the composite of all-cause mortality,
nonfatal type 1 myocardial infarction, any unplanned revascularization, and
cerebrovascular events (MACCE) at 1-year post intervention.
Secondary outcome
• Composite clinical outcome of all-cause mortality, nonfatal type 1 myocardial
infarction, any unplanned revascularization, and cerebrovascular events (MACCE)
at 30 days, 2 and 5 years post intervention.
• All-cause mortality at 30 days, 1, 2 and 5 years
• Myocardial Infarction (Q-wave and non Q-wave MI) at 30 days, 1, 2 and 5 years
• Any revascularization procedure, target lesion revascularization (TLR),
Target Vessel Revascularization (TVR) and non-TVR at 30 days, 1, 2 and 5 years
• Major bleeding (not related to coronary-artery bypass grafting, BARC 3-5) at
30 days and 1 year
• Safety and efficacy of immediate complete revascularization in patient
subgroups with specific demographics, clinical indications and/or vessel- or
lesion characteristic
• Net adverse clinical events at 30 days and one year, a composite of:
• Major bleeding (not related to coronary-artery bypass grafting, BARC
3-5)
• All-cause mortality, myocardial infarction or stroke
• Need for renal replacement therapy at 30 days
• Quality of Life at 30 days and 1 year
Health status will be compared between the 2 groups using the Seattle Angina
Questionnaire (SAQ) and the EQ 5D (EuroQol) assessment at 1 and 12 months post
procedure.
Background summary
Invasive coronary angiography followed by primary percutaneous coronary
intervention is the treatment of choice in patient presenting with STEMI-ACS1
and NSTEMI-ACS2. Up to 60 percent of these patients have multivessel disease on
angiography3-5. Patients with multivessel disease have a worse prognosis than
in those with culprit vessel disease only5. It has been debated whether a
complete or culprit artery only revascularization strategy is better.
Retrospective data in STEMI patients suggested a lower mortality in patients
that were treated with culprit artery only compared with multivessel PCI during
index procedure6. Since then, four randomized controlled trials have addressed
this question in STEMI population; Randomized Trial of Preventive Angioplasty
in Acute Myocardial Infarction (PRAMI) trial (n = 465, 23 months follow-up)7,
the Randomized trial of complete versus lesion-only revascularization in
patients undergoing primary percutaneous coronary intervention for STEMI and
multivessel disease (CvLPRIT) (n = 296, 12months follow-up)8, the Complete
revascularisation versus treatment of the culprit lesion only in patients with
ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3-
PRIMULTI) trial (n = 627, 27months follow-up)9, and the Fractional Flow
Reserve-Guided Multivessel Angioplasty in Myocardial Infarction (Compare-Acute)
trial (n = 885, 12 months follow-up)10. PCI of the non-infarct related artery
was performed at the index procedure ((PRAMI and Compare-Acute), staged before
discharge (DANAMI-3-PRIMULTI) or at any time during hospitalization (CvLPRIT).
Indication for PCI was significant stenosis as assessed by angiography (PRAMI
and CvLPRIT) or FFR (DANAMI-3-PRIMULTI and COMPARE-ACUTE). There was a
significant reduction in primary outcome in all four trials in favor of
complete revascularization. However, this was mainly driven by *soft*
endpoints. There was no significant reduction in total mortality or myocardial
infarction. Based on the results for these four trials, the 2017 ESC STEMI-ACS
guidelines give a class II, LOE A, indication for routine revascularization in
STEMI patients with multivessel disease, including those presenting with
cardiogenic shock1. However, an important shortcoming of the abovementioned
studies is the absence of a staged complete revascularization arm. As there is
no data that compare immediate and staged complete revascularization, the
guidelines don*t advise on when to perform non infarct related artery
revascularization.
Data regarding optimal treatment in NSTEMI-ACS is more scarce and a RCT is
lacking. In an observational study by Shishesbor and coworkers, they showed
that nonculprit multivessel stenting reduced future revascularization rate but
this was not associated with lower death rate or myocardial infarction rate11.
Recently, a substudy from the Bleeding complications in a Multicenter registry
of patients discharged with diagnosis of acute coronary syndrome (BleeMACS)
registry (N=4520 patients, 1459 NSTEMI) was published12. They showed that in
NSTEMI patients, complete revascularization was associated with a significant
lower rate of death (4.5% vs. 8.5%; p=0.002), re-AMI (3.7% vs. 6.6%; p=0.016)
and MACE (8.1% vs. 13.9%; p=0.001) at one year follow up. The 2015 ESC
NSTEMI-ACS guidelines not specifically advise a culprit only or multivessel PCI
strategy. Moreover, they advise to base revascularization strategy on patients
clinical status and co-morbidities, as well as disease severity, Class II, LEO
B. Interestingly, in contrast to the STEMI population, in NSTEMI population
there is a RCT addressing whether staged or direct complete revascularization
is better, the Single-Staged Compared With Multi-Staged PCI in Multivessel
NSTEMI Patients: The SMILE Trial (N=584 patients)13. There was a significant
reduction in primary endpoint 1S-PCI: n = 36 [13.63%] vs. MS-PCI: n = 61
[23.19%]; hazard ratio [HR]: 0.549 [95% confidence interval (CI): 0.363 to
0.828]; p = 0.004) at one year follow up. This was mainly driven by a reduction
in target vessel revascularization. There was no significant difference in
cardiac death or myocardial infarction between the both groups. This finding
deserves further investigation, because the TVR rate (15.4% at 1 year) in the
multistage group was unprecedentedly high in the era of current-generation
drug-eluting stents.
There is no publication specifically addressing the patients with unstable
angina regarding the subject of complete or incomplete revascularization or
timing of revascularization.
Taken together, complete revascularization in ACS patients seems reasonable,
but timing of revascularization is unknown.
Study objective
To test whether immediate complete revascularization is non-inferior to staged
(but within six weeks after index procedure) complete revascularization in ACS
patients with multivessel disease
Study design
This study is a prospective, multicenter, randomized, two-arm, international,
open-label, non-inferiority study. Due to the design characteristics of the
study, the study investigators and operators cannot be blinded. However, the
clinical event adjudication committee, consisting of cardiologists who are not
participating in the study, will be blinded for the treatment arm of the
patients to avoid a potential bias in the adjudication process of events
Intervention
At the index procedure, the culprit lesion (cause of complaints/acute coronary
syndrome) will be treated according to standard of care with a Biotronik Orsiro
DES (Sirolimus-Eluting stent). If there are additional significant lesions
besides the culprit lesion, patients will be randomized to direct complete
revascularization or staged complete revascularization. In the direct complete
revascularization group all lesions will be treated during the index procedure.
In the staged complete revascularization group, only the culprit lesion will be
treated during the index procedure. The remaining significant lesions will be
treated later but within six weeks after the index procedure. In both arms the
additional lesions will also be treated with Biotronik Orsiro DES
(Sirolimus-Eluting stent).
Study burden and risks
Participation contributes to expansion of the knowledge base with respect to
best treatment of patients presenting with an acute coronary syndrome and more
than one narrowed artery, which may assist physicians in their choice of
treating any future patients. When participating in this study, you will have
more medical check-ups than when you would not be participating in the study.
In addition, you will be treated with a stent that was developed with the
latest technology.
Patients will be implanted with two or more Biotronik Orsiro DES,
Sirolimus-Eluting stent systems. This stent model is approved to be used.
Therefore there is no higher risk associated with implantation of these systems
in this study. The risk associated with stent implantation in general is among
others dependent on the severity of the narrowing(s) in your coronary arteries,
your symptoms but also other factors.
For this study data from patients medical files will be gathered. There will be
no additional tests as compared to normal procedures.
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
1. Age >= 18 years or minimum age as required by local regulations
2. The patient is an acceptable candidate for treatment with a drug eluting
stent in accordance with the applicable guidelines on percutaneous coronary
interventions, manufacturer*s Instructions for Use and the Declaration of
Helsinki
3. Patient indication, lesion length and vessel diameter of the target
lesion(s) are according to the *Instructions for Use* that comes with every
Biotronik Orsiro (Sirolimus-Eluting stent) system. Patients should qualify for
both systems before randomization
4. The patient is willing and able to cooperate with study procedures and
required follow up
visits
5. The subject or legal representative has been informed of the nature of the
study and agrees to its provisions and has provided an EC approved written
informed consent, including data privacy authorization
6. diagnosed Acute coronary syndrome according to ESC guidelines/criteria
7. Multivessel disease
Exclusion criteria
• Age <18 years and > 85 years
• Single coronary vessel disease
• Patients in cardiogenic shock
• Patients who cannot give informed consent or have a life expectancy of less
than 1year
• Absolute contraindications or allergy that cannot be pre-medicated, to
iodinated contrast or to any of the study medications, including both aspirin
and P2Y12 inhibitors.
• Enrollment in another study with another investigational device or drug trial
that has not reached the primary endpoint The patient may only be enrolled
once in the BioVAsc study
• PCI in the previous 30 days.
• Presence of a chronic total occlusion
• Women of childbearing potential who do not have a negative pregnancy test
within 7 days before the procedure and women who are breastfeeding.
• Planned surgery within 6 months of PCI unless dual antiplatelet therapy is
maintained throughout the peri-surgical period
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 | NL64686.078.18 |