Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04291287 |
| Other study ID # |
TRIDUAL-PCI18122019 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 25, 2020 |
| Est. completion date |
September 30, 2022 |
Study information
| Verified date |
March 2020 |
| Source |
Scientific Institute San Raffaele |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Aim of this study is to describe clinical and procedural characteristics of real-world
population initiated on triple antithrombotic therapy (double antiplatelet
therapy+anticoagulant) or double antithrombotic therapy (single antiplatelet
therapy+anticoagulant) after percutaneous coronary intervention (PCI). Investigator's driven
trial, retrospective (2015-2019), multicenter Italian registry. Baseline clinical
characteristics as well as procedural details will be collected retrospectively. Follow-up
data (minimum 6 months and maximum 5 years follow-up) will focus on combined rates of stent
thrombosis and myocardial infarction (primary endpoint).
Description:
INTRODUCTION The optimal antithrombotic therapy (combination of anticoagulants and
antiplatelets drugs) for patients with non valvular atrial fibrillation (NVAF) after coronary
stenting is unknown. In the last years, four randomized controlled trials compared double
antithrombotic therapy with Direct Oral Anti-Coagulants (DOACs) and antiplatelet agent versus
antithrombotic therapy including warfarin in patients with NVAF undergoing percutaneous
coronary intervention (PCI).1-4 However, none of these trial reported the angiographic
features of treated coronary lesions nor other PCI details (as stent location, stent number,
stent length, type of bifurcation etc). All these characteristics are established
determinants of PCI related thrombotic risk. Moreover, all trials were underpowered for the
evaluation of stent thrombosis, instead were powered and focused on major bleeding events.
Finally, different antithrombotic regimens with DOACs and antiplatelet agent (triple or dual
therapy) have not been compared yet.
3. STUDY RATIONALE: Double platelets suppressive agents combined with oral anticoagulation
(triple antithrombotic therapy) was the gold standard after PCI with stent implantation in
patients with NVAF. Dual antiplatelet therapy (DAPT) is recommended to reduce the risk of
ischaemic complications in patients undergoing PCI and the combination of anticoagulant with
DAPT, a strategy generally called triple antithrombotic therapy, increases the bleeding risks
compared with the use of anticoagulant or DAPT alone. Therefore, research has focused on
choosing a treatment strategy that provides the optimal balance between ischaemic and
bleeding occurrences.1,2 The use of Direct Oral Anti-Coagulants (DOACs) instead of
traditional anticoagulants (warfarin and acenocumarol) is expanding, but their proper
management in patients PCI with stent implantation and concomitant indication for
antiplatelet therapy is still not completely clear. Current European guidelines are still
based on weak data. Recently, 4 randomized controlled trials compared double antithrombotic
therapy with DOACs and antiplatelet agent versus antithrombotic therapy including warfarin in
patients with NVAF undergoing PCI.1-4 None of these studies reported the angiographic
features of treated coronary lesions nor other PCI details (stent location, stent number,
stent length, type of bifurcation etc). All these are established determinants of PCI-related
thrombotic risk. Moreover, all RCTs were underpowered for the evaluation of stent thrombosis,
instead were powered and focused on major bleeding events. Finally, different antithrombotic
regimens with DOACs and antiplatelet agent (triple or dual therapy) have not been compared
yet. Therefore, the aim of this investigator's driven trial, retrospective, multicenter
Italian registry is to describe clinical and procedural characteristics of a real-world large
population initiated, on the basis of the local practice, the triple or double antithrombotic
therapy after PCI, comparing different anticoagulant regimens (DOACs or
warfarin/acenocumarol) in terms of efficacy (coronary stent thrombosis and myocardial
infarction) and safety (major bleeding or clinically relevant non-major bleeding).
4. DETAILED DESCRIPTION This Italian, multicenter, retrospective observational study is aimed
to evaluate the management of antithrombotic therapy with antiplatelet therapy (single or
dual) and concomitant anticoagulant therapy (with direct oral anticoagulants, DOACs, or
warfarin/acenocumarol) in patients with NVAF undergoing elective or urgent PCI with stent
implantation and the adverse events (coronary stent thrombosis, myocardial infarction and
major bleeding) associated with. The registry include all consecutive patients with NVAF
treated in the last 5 years by PCI with stent (drug-eluting stent and/or bare metal stent).
The aim of the study is to evaluate the safety and efficacy of triple or dual antithrombotic
therapy in patients taking Triple antithrombotic therapy (aspirin and a P2Y12 inhibitor, in
addition to either a DOACs or warfarin/acenocumarol) or Dual antithrombotic therapy (aspirin
or P2Y12 inhibitor in addition to either a DOACs or warfarin/acenocumarol) for the prevention
of adverse events after PCI in patients with NVAF (or atrial flutter).
Adenosine diphosphate (ADP) receptor antagonists (or P2Y12 inhibitors) therapy include:
- Clopidogrel (Plavix®)
- Prasugrel (Efient®)
- Ticagrelor (Brilique®)
DOACs therapy include:
- Apixaban (Eliquis®)
- Dabigatran (Pradaxa®)
- Edoxaban (Lixiana®)
- Rivaroxaban (Xarelto®).
Oral anticoagulant therapy (OAT) include:
- Warfarin (Counmadin®)
- Acenocumarol (Sintrom®) RESEARCH QUESTION AND OBJECTIVES 5.1 PRIMARY ENDPOINT
The primary endpoint is the safety composite endpoint of the occurrence of stent thrombosis
and acute myocardial infarction (MI) at 1 year.
Type of stent thrombosis according to Academic Research Consortium (ARC) criteria:
- Definite or confirmed event (symptoms suggestive of an acute coronary syndrome and
angiographic or pathologic confirmation of stent thrombosis)
- Probable event (unexplained death within 30 days or target vessel myocardial infarction
without angiographic confirmation of stent thrombosis)
- Possible event (any unexplained death after 30 days)
Based on the elapsed time since stent implantation stent thrombosis can be classified as:
- Early (0-30 days post stent implantation)
- Late (>30 days)
- Very late (>12 months) Often, early stent thrombosis is further subdivided into acute
(<24 hours) and subacute (1-30 days) events.
Type of acute MI (STEMI and NSTEMI) is classified according to the Joint ESC/ACCF/AHA/ WHF
Joint Task Force for the Universal Definition of Myocardial Infarction.
- Spontaneous MI (Type 1) requires a) Detection of a rise and/or fall of cardiac biomarker
values (preferably cTn) with at least 1 value >99th percentile of the URL and b) At
least 1 of the following: 1) Symptoms of myocardial ischemia 2) New or presumed new
significant ST-segment-T wave (ST-T) changes or new LBBB on the ECG 3) Development of
pathological Q waves on the ECG 4) Imaging evidence of new loss of viable myocardium or
new regional wall motion abnormality 5) Identification of an intracoronary thrombus by
angiography or autopsy.
- PCI related MI (Type 4a or periprocedural MI): MI associated with and occurring within
48 h of PCI, with elevation of cardiac biomarker values to >5 × 99th percentile of the
URL in patients with normal baseline values (=99th percentile URL), or a rise of
[cardiac biomarker] values =20% if baseline values are elevated and are stable or
falling. This classification also requires at least 1 of the following: a) Symptoms
suggestive of myocardial ischemia (ie, prolonged ischemia =20min) b) New ischemic
changes on ECG or new LBBB c) Angiographic loss of patency of a major coronary artery or
a side branch or persistent slow flow or no flow or embolization d) Imaging evidence of
new loss of viable myocardium or new regional wall motion abnormality.
- Stent thrombosis related MI (Type 4b): MI associated with stent thrombosis as detected
by coronary angiography or at autopsy, where symptoms suggestive of myocardial ischemia
are present, and with a rise and/or fall of [cardiac biomarker] values, with at least 1
value >99th percentile of the URL.
- Stent restenosis related MI (Type 4c): MI associated with stent restenosis as detected
by coronary angiography or at autopsy, occurring >48 h without evidence of stent
thrombosis but with symptoms suggestive of myocardial ischemia, and with elevation of
[cardiac biomarker] values to >99th percentile of the URL. This classification also
requires the following: a) Does not meet criteria for any other classification of MI b)
Presence of a =50% stenosis at the site of previous successful stent PCI or a complex
lesion and no other significant obstructive CAD of greater severity following 1)
Initially successful stent deployment, or 2) Dilation of a coronary artery stenosis with
balloon angioplasty to <50% stenosis.
5.2 SECONDARY ENDPOINT
- Incidence of major bleeding and clinically relevant non-major events according to
International Society Thrombosis Haemostasis (ISTH) criteria [Time Frame: up to 1-year
since the initiation of antithrombotic therapy]
- Incidence of thromboembolic events (stroke, TIA, peripheral embolism) [Time Frame: up to
1-year since the initiation of antithrombotic therapy]
- Myocardial infarction (STEMI and NSTEMI) [Time Frame: up to 1-year since the initiation
of antithrombotic therapy] ELIGIBILITY CRITERIA 6.1 INCLUSION CRITERIA
- Patients aged 18 years or older
- Patients with a diagnosis of non valvular atrial fibrillation (or atrial flutter
treated) with PCI and stent (drug eluting or bare metal stent) requiring triple
antithrombotic therapy (double antiplatelets agents and oral anticoagulation) or dual
antithrombotic therapy (single antiplatelet agent and oral anticoagulation)
- Patients with NVAF treated for elective PCI (in the contest of chronic coronary
syndromes) or urgent (in the contest of an acute coronary syndromes: STEMI, NSTEMI,
unstable angina).
- Patients who give the informed consent.
6.2 EXCLUSION CRITERIA • Patients with less than 6 months of clinical follow-up availability
7.0 SAFETY ADVERSE EVENTS/ADVERSE REACTIONS
No individual case safety reporting exists for this analysis, however, all adverse events
evaluated as primary and secondary endpoints will be collected in the CRF, analyzed and
described in the final report. If it may raise a safety signal, it will be notified to each
Ethical Committees and, following the local practice of each center, reported to the
competent Authority.
STATISTICAL CONSIDERATIONS Continuous variables will be reported as mean±standard deviation
(SD). Categorical variables (such as frequencies or percentages) will be compared with χ2 or
the Fisher exact test as appropriate. Event-free survival will be evaluated according to the
unadjusted Kaplan-Meier method and survivals among groups will be compared using log-rank
test (Cox-Mantel test). Multivariable Cox-regression analysis will be performed to analyze
the influence of relevant variables on primary and secondary endpoints.
Based upon the assumption that 1500 patients with non valvular atrial fibrillation (or atrial
flutter) treated with PCI and stent will be enrolled and the expected incidence of the
primary endpoint is 1.5% during up to 1-year follow up, the following table provides the
precision of 95% confidence intervals for the endpoint of the study:
Expected incidence Lower limit of 95% CI Upper limit of 95% CI 1.5% 0.9% 2.1% 1.2% 0.7% 1.7%
1% 0.5% 1.5%
