1-month vs 12-month DAPT for ACS Patients Who Underwent PCI Stratified by IVUS: IVUS-ACS and ULTIMATE-DAPT Trials

Study Overview
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Brief Summary
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Prospective, multicenter, randomized, double-blind, placebo-controlled trials.

Detailed Description
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A total of 3486 subjects with ACS who met inclusion criteria and do not have any exclusion criterion will be randomized to IVUS- or Angiography-guidance group (first randomization). In the IVUS-guidance group, IVUS will be used to evaluate the lesion's specificity and to measure lesion length, landing zone, and reference vessel diameter prior-to stenting; and to assess stent expansion, extension, apposition, and possible complications after stent implantation. The IVUS- defined criteria for the optimal stent deployment included: 1) the minimal stent area (MSA) in the stented segment is >5.0 mm^2, or 90% of the MLA at the distal reference segments; 2) plaque burden 5-mm proximal or distal to the stent edge is <55%; and 3) absence of >Type B edge dissection. Further treatment will be required if stenting procedure is defined as suboptimal according to IVUS definition. IVUS will be not allowed to be used in the Angiography-guidance group. Those patients who have had no death, STEMI, stroke, ST, TVR or major bleeding (BARC 3 or 5) within 30 days and have continued on aspirin and ticagrelor for 30 days without interruption for >48 hours will be randomized 1:1 to: Ticagrelor plus+ matching placebo for an additional 11 months (SAPT group) Ticagrelor plus aspirin (study drug) for an additional 11 months (DAPT group) Follow-up of all subjects will continue for 1 year with an option for additional follow-up to 3 years.

Official Title
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Comparison of 1-month Versus 12-month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents Guided by Either Intravascular Ultrasound or Angiography in Patients With Acute Coronary Syndrome: The Prospective, Multicenter, Randomized, Placebo-controlled IVUS-ACS and ULTIMATE-DAPT Trials

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: AntiPlatelet therapy
* Procedure: Percutaneous coronary intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrollment into the study will require meeting at least one of these clinical syndromes within 1 month. Unstable angina, defined as rest pain for 5-30 minutes or deteriorative exertional angina with either a) transient ST segment depression or elevation, or b) angiography showing a visually estimated diameter stenosis ≥90% or a ruptured plaque or thrombotic lesion Non-ST elevation myocardial infarction (NSTEMI), defined as positive troponin consistent with clinical syndrome. ST elevation MI (STEMI) Exclusion Criteria: Unable or unwilling to provide informed consent Stroke within 3 months or any permanent neurologic deficit, and prior intracranial bleed, or any intracranial disease such as aneurysm or fistula Previous coronary artery bypass graft (CABG) Any planned surgery within 90 days Any reason why any antiplatelet therapy might need to be discontinued within 12 months Severe chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) < 20 ml/min/1.73m^2 Need for chronic oral anticoagulation (warfarin/coumadin or direct oral anticoagulants) Platelet count < 100,000 mm^3 Contraindication to aspirin Contraindication to ticagrelor Liver cirrhosis Women of child-bearing potential Life expectancy < 1 year Any condition likely to interfere with study processes including medication compliance or follow-up visits (e.g. dementia, alcohol abuse, severe frailty, long distance to travel for follow-up visits, etc.)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will undergo 1:1 randomization (first randomization) to either IVUS-guided DES implantation which will be the treatment group or Angio-guided DES implantation which will be the control group based on an online Clinical Research Data Management Platform. The initiation of the trial is defined as the time of randomization. After study subjects' enrollment and randomization, the study intervention will take place immediately. The follow-up visits for the primary TVF endpoint are scheduled at 1, 4, 6, and 12 months after the index procedure. Patients will undergo 1:1 randomization (second randomization) to either SAPT which will be the treatment group or DAPT which will be the control group based on an online Clinical Research Data Management Platform. The follow-up visits for the primary superiority bleeding endpoint and non-inferiority ischemic endpoint are scheduled at 3, 5, and 11 months after the second randomization.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IVUS-guidance<br>In the IVUS-guided DES implantation group, optimal stent deployment criteria included: 1) the MLA in the stented segment is >5.0 mm^2, or 90% of the MLA at the distal reference segments; 2) plaque burden 5-mm proximal or distal to the stent edge is <55%; and 3) absence of >=Type B edge dissection. Further treatment will be required if any of those 3 criteria was not met. | Drug: AntiPlatelet therapy<br>* AntiPlatelet therapy with ticagrelor + aspirin or ticagrelor alone.<br>* Other names: ticagrelor, aspirin;Procedure: Percutaneous coronary intervention<br>* PCI with DES implantation<br>* Other names: PCI;|
| Active Comparator: Angiography-guidance<br>In the Angiography-guided DES implantation group, stent diameter and length will be selected by visual estimation with a stent/artery ratio of 1.1:1.0. Post-dilation with a noncompliant balloon (balloon/stent diameter=1.0:1.0) inflated at >18 atm will be performed for all lesions. Angiographic success is defined as Thrombolysis In Myocardial Infarction (TIMI) grade 3, residual stenosis <20%, and the absence of >Type B dissection. | Drug: AntiPlatelet therapy<br>* AntiPlatelet therapy with ticagrelor + aspirin or ticagrelor alone.<br>* Other names: ticagrelor, aspirin;Procedure: Percutaneous coronary intervention<br>* PCI with DES implantation<br>* Other names: PCI;|
| Experimental: SAPT group<br>Ticagrelor + aspirin for 1 month followed by ticagrelor plus matching placebo for an additional 11 months. | Drug: AntiPlatelet therapy<br>* AntiPlatelet therapy with ticagrelor + aspirin or ticagrelor alone.<br>* Other names: ticagrelor, aspirin;Procedure: Percutaneous coronary intervention<br>* PCI with DES implantation<br>* Other names: PCI;|
| Active Comparator: DAPT group<br>Ticagrelor + aspirin for 12 month. | Drug: AntiPlatelet therapy<br>* AntiPlatelet therapy with ticagrelor + aspirin or ticagrelor alone.<br>* Other names: ticagrelor, aspirin;Procedure: Percutaneous coronary intervention<br>* PCI with DES implantation<br>* Other names: PCI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target vessel failure (TVF) | The difference in TVF will be calculated from 0 month to 12 months between IVUS- and Angiography guidance groups. | 12 months | 
| Clinically-relevant bleeding | The difference in clinically-relevant bleeding (BARC ≥2) will be calculated from 1 month to 12 months between SAPT and DAPT groups. | 11 months | 
| Major adverse cardiovascular and cerebrovascular events (MACCE) | The difference in MACCE will be calculated from 1 month to 12 months between SAPT and DAPT groups. | 11 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net adverse clinical events (NACE) | The difference in NACE between IVUS- and Angiography guidance groups, or SAPT and DAPT groups. | 12 months |