This study has been transitioned to CTIS with ID 2024-515883-30-00 check the CTIS register for the current data. The primary objective of this study is to prove noninferiority regarding safety and effectiveness of 30-45 day of DAPT followed by…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The first primary objective of this Open-label, Randomized, Controlled Clinical
Trial is to demonstrate the non inferority of a Prasugrel-based short DAPT
(30-45 days) followed by 11-month Prasugrel monotherapy versus standard DAPT
regimen by assessing:
- Incidence of Net Adverse Clinical Events (NACE) at 11 months post DAPT
randomization as composite of death, MI, stroke or BARC bleeding 3 or 5
The co-primary objective is to demonstrate in patients with multivessel disease
the superiority of an Optical Coherence Tomography (OCT)-guided
revascularization completion as compared to a standard angiography-guided
revascularization completion by assessing:
- Post-procedural Minimal Stent Area (MSA)
Secondary outcome
With respect to the antithrombotic therapy analysis, the secondary exploratory
objectives primarily include the assessment of the primary endpoint for
superiority if non-inferiority is demonstrated and the assessment of
differences between the two antithrombotic regimens compared in the trial for
the following endpoints (key secondary endpoints):
• Composite of major adverse cardiac and cerebrovascular events (MACCE) defined
as cardiovascular death, myocardial infarction, or ischaemic stroke
• BARC type 3 or 5 events
- Incidence of stent thrombosis (definite or probable as defined by the
Academic Research Consortium)
With respect to the imaging-based analysis, the secondary exploratory
objectives include the assessment of differences between OCT- and
angiography-guided revascularization completion in terms of 12-month target
vessel failure (TVF), defined as the composite of cardiac death, target vessel
myocardial infarction, or ischemia-driven target vessel revascularization.
In the subgroup of patients with multivessel disease, the interaction between
antithrombotic therapy regimens (i.e. short DAPT followed by Prasugrel
monotherapy versus standard DAPT) and the type of guidance to achieve
revascularization completeness (i.e., OCT- versus angiography-guided) for the
primary and key secondary endpoints will be formally explored by Cox
proportional hazards regression models including the two factors as covariates
alongside their interaction term.
Background summary
A dual antiplatelet treatment regimen with a platelet P2Y12 adenosine
diphosphate (ADP) receptor antagonist in addition to the cyclooxygenase
inhibitor acetylsalicylic acid (ASA) represents the cornerstone of treatment of
acute coronary syndrome (ACS) patients. The synergistic effect of a dual
antiplatelet therapy (DAPT) has been shown to be superior than only aspirin in
clinical trials enrolling ACS patients.
Several concerns raised over the heterogeneous response variability and delayed
onset of action of the second-generation thienopyridine Clopidogrel, has led to
the clinical development of third generation P2Y12 inhibitors Prasugrel and
Ticagrelor.
The new faster-acting and more potent antiplatelet agents may justify
revisiting the concept of aspirin as the cornerstone of DAPT.
The balance between protecting from ischemic events while avoiding bleeding
complications following PCI is a major dilemma in current practice.
New generation Drug Eluting Stents (DES) and the use of intravascular imaging
to optimize percuteanous coronary intervention (PCI) result, are associated
with lower stent thrombosis event rates, potentially allowing for a less
intense anti-thrombotic therapy.
The role of OCT-guided PCI in reducing the rate of MACE is well established in
literature (Kuku). Intravascular imaging can help optimize the PCI results by
helping achieve adequate stent expansion and stent strut apposition, by
enabling identification of edge dissections as well as initial and residual
thrombus burden.
However, the use of intravascular imaging in the context of complete
revascularization and short DAPT regimen has received limited study.
Study objective
This study has been transitioned to CTIS with ID 2024-515883-30-00 check the CTIS register for the current data.
The primary objective of this study is to prove noninferiority regarding safety
and effectiveness of 30-45 day of DAPT followed by Prasugrel-monotherapy versus
standard 12 months of DAPT in patients admitted for STEMI treated by primary
PCI.
The ancillary objective of the study is to prove that OCT-guided
revascularization completion by staged PCI is superior to an angio-guided
approach in patients with multivessel disease who have received guideline-based
treatment of the culprit lesion.
Study design
Randomized, open-label, phase IV, multicenter trial.
Intervention
All eligible patients will receive ASA as per standard of care and
P2Y12-loading dose followed by 30-45 days DAPT (ASA + Prasugrel)
Enrolment will be performed in all STEMI patients undergoing PCI.
DAPT Randomization will be performed between Prasugrel monotherapy and standard
DAPT regimen with a randomization sequence of 1:1 in all patients who remain
stable on DAPT (ASA and prasugrel) and without ischemic or bleeding events till
randomization between 30 to 45 days after index procedure.
-Short DAPT arm: 11 months Prasugrel monotherapy post DAPT randomization
-Control group: 11 months DAPT post DAPT randomization
Patients with multivessel disease (MVD) will be also randomized to either:
-OCT-guided complete revascularization
or
-Angio-guided complete revascularization
Study burden and risks
STEMI patients are included after successful revascularization of the culprit
vessel and before hospital discharge.
Patients who have stenosis in multiple vessels will be randomized before the
staged treatment of the non-culprit leasion to either OCT guided or Angio
guided PCI. Patients who have undergone a complete revascularization during
index PCI will not be included in the study.
Eligible subjects will be randomized during the hospital visit at 1 month in a
1:1 ratio to one of the following two groups:
• Short DAPT + aspirin discontinuation: patient discontinues aspirin
immediately and continues on prasugrel alone for the next 11 months.
• Control group: 11 months prasugrel + aspirin
The subjects who are not eligible for randomization (eg due to a serious
ischemic event or bleeding, serious adverse reaction, new need for COC,...)
will not be randomized and their study participation will be terminated.
Follow-up visits are scheduled at 1 month, 2 months, 12 and 36 months after the
PCI, with 2 and 36 months visits being allowed by telephone.
Patients are informed that data is collected at the index PCI and at scheduled
follow-up visits and at unscheduled visits.
The investigator monitors the occurrence of serious adverse events (SAEs) for
each patient throughout the study. In this protocol, reporting of SAEs begins
immediately upon study inclusion.
The additional burden for the patient are the planned follow-up visits at
1-2-12-36 months after the PCI.
The potential risks and inconveniences associated with the study participation
are similar to those seen with commercially approved stents, and to current
routine treatment for the patients assigned to the control group.
For the patients assigned to the Short DAPT + Aspirin Discontinuation arm
(Short DAPT + Aspirin Discontinuation), there is a potential increased risk of
adverse events caused by blood clots or oxygen starvation.
A 'short DAPT + aspirin discontinuation' treatment may have the benefit of a
lower risk of bleeding. A short DAPT treatment is expected to provide
comparable protection against a heart attack as a longer DAPT duration (DAPT of
12 months), but with less bleeding.
With the OCT imaging technique, the coronary artery is visualized from the
inside. Images are collected and the blood flows through the narrowed arteries
are measured. This data is used when selecting the correct stent size and when
placing the stent and to verify that the stent has been placed correctly. In
addition to standard angiography, this technique could have a beneficial effect
in the treatment of the narrowing of the coronary arteries.
Maasstadweg 21
Rotterdam 3079 DZ
NL
Maasstadweg 21
Rotterdam 3079 DZ
NL
Listed location countries
Age
Inclusion criteria
Inclusion Criteria at index procedure
All STEMI patients who are planned to be treated with PCI:
ST segment elevation myocardial infarction:
Chest discomfort suggestive of cardiac ischemia >=20 min at rest with 1 of the
following ECG features:
• ST segment elevation >=2 contiguous ECG leads
• new or presumably new left bundle branch block
Inclusion Criteria at 30-45 days
• All patients who have provided informed consent
• Compliance to DAPT with no regimen modifications (Non-adherence Academic
Research Consortium 0)
• No occurrence of significant event (such as MI, unplanned revascularisation,
stent thrombosis, stroke, major vascular complication/bleeding BARC Types 3 or
greater).
• Successful revascularization: - Successful delivery and deployment of the
Study device(s), with final residual stenosis of <30% (visually) for all target
lesions.
• Complete revascularization performed when more than 1 significant lesion
during staged procedure(s) occurring within 15 days from the index procedure.
Physiologic assessment highly recommended for lesions with stenosis between 50%
and 90%.
Exclusion criteria
- Patients on oral anticoagulation
- Contraindication to P2Y12 inhibitors and/or to Cardioaspirin or to any of the
excipients (hypersensitivity, history of any stroke or transient ischemic
attack within the last 12 months, active bleeding or haemorrhagic diathesis,
fibrin-specific fibrinolytic therapy less than 24 h before randomization,
severe hepatic dysfunction (Child-Pugh C), history of asthma induced by the
administration of salicylates or substances with a similar action, notably
non-steroidal anti-inflammatory medicines, history of gastrointestinal
perforation or acute gastrointestinal ulcers, severe cardiac failure (NYHA
grade III or IV), combination with methotrexate at doses of 15 mg/week or
more).
- Patients who have received P2Y12 inhibitors other than Prasugrel in the
ambulance (Ticagrelor or Clopidogrel loading dose) or are already on P2Y12
inhibitors, may be enrolled in the protocol, provided that the Prasugrel
loading dose is administered at admission, according to current guidelines
recommendations (see section 5.2.2).
- Concomitant oral or i.v. therapy with strong CYP3A inhibitors (e.g.,
ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin,
nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir,
grapefruit juice >1L/day), CYP3A substrates with narrow therapeutic indices
(e.g., cyclosporine, quinidine), or strong CYP3A inducers (e.g., rifampin)
- rifampicin, phenytoin, carbamazepine, dexamethason, phenobarbital
- Platelet count <100.000/µL at the time of screening
- Anemia (hemoglobin <10 g/dL) at the time of screening
- Comorbidities associated with life expectancy <1 year
- Pregnancy, giving birth within the last 90 days, or lactation (see appendix
III for women of childbearing potential)
- PCI indication for stent thrombosis or previous history of definite stent
thrombosis
- Non-deferrable major surgery on DAPT after PCI
- Cardiogenic shock
- Out of hospital cardiac arrest (OHCA) unless survivors of ventricular
arrythmia with prompt return of spontaneous circulation (ROSC)
- Patients with severe renal impairment: creatinine clearance <=30 ml/min/1.73
m2 (as calculated by MDRD formula for estimated GFR).
- Patients participating in another interventional (device of drug trial)
within the previous 12 months or patients to whom an investigational drug was
administered in the 30 days prior to screening, or 5 half-lives of the study
drug, whichever is longer.
- No informed consent
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 |
|---|---|
| EU-CTR | CTIS2024-515883-30-00 |
| EudraCT | EUCTR2021-005499-20-NL |
| ClinicalTrials.gov | NCT05491200 |
| CCMO | NL79373.100.22 |