An Interventional Strategy for Non-culprit Lesions With Major Vulnerability Criteria Identified by Optical Coherence Tomography in Patients With Acute Coronary Syndrome (the INTER-CLIMA Trial)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 1,425
- 试验地点
- 34
- 主要终点
- Number of patients with cardiac death or non-fatal spontaneous target-vessel myocardial infarction
研究概览
简要总结
The INTERCLIMA (Interventional Strategy for Non-culprit Lesions With Major Vulnerability Criteria Identified by Optical Coherence Tomography in Patients With Acute Coronary Syndrome) is a multi-center, prospective, randomized trial of optical coherence tomography (OCT)-based versus physiology-based (i.e. fractional flow reserve[FFR]/instantaneous Wave-Free Ratio[iFR]/resting full-cycle ratio[RFR]) treatment of intermediate (40-70% diameter stenosis), non-culprit coronary lesions in acute coronary syndrome (ACS) patients undergoing coronary angiography. About 1420 patients with ACS will be randomized into the study at approximately 40 sites worldwide.
详细描述
The optimal strategy in patients with intermediate stenosis (40-70% diameter stenosis) at coronary angiography is currently under debate. Pure angiographic stenosis evaluation is often inadequate and alternative assessments of coronary plaques entered the clinical practice, such as functional assessment (FFR/iFR/RFR) and intravascular imaging (OCT and intravascular ultrasound [IVUS]). Based on preliminary data, current American College of Cardiology (ACC) and American Heart Association (AHA) revascularization guidelines recommend the use of flow fractional reserve (FFR, class IIa of evidence) to assess angiographic intermediate coronary lesions in patients with stable ischemic heart disease and guide intervention. However, controversial data has recently emerged on the role of functional assessment of intermediate coronary lesions in both acute and chronic settings. On the other hand, in recent studies, the presence of coronary plaques with vulnerability criteria at OCT identified patients at high risk of cardiac mortality and target vessel MI. This study aims to assess the clinical effectiveness of an OCT-based strategy to guide revascularization in non-culprit intermediate coronary stenosis in patients with acute coronary syndrome (ACS), on the basis of the presence of morphological markers of plaque vulnerability. Patients with intermediate coronary lesions in non-culprit intervention-naïve major coronary segments (diameter ≥2.5 mm) and fulfilling all inclusion/exclusion criteria will be eligible. Enrolled patients will be randomized 1:1 to either OCT or FFR/RFR/iFR based treatment. In the OCT-guided arm, non-culprit intermediate lesions will be treated with PCI with implantation of a second-generation drug eluting stent (DES) when a FCT <75 µm plus at least 2 of 3 other OCT criteria of plaque vulnerability (i.e., MLA <3.5 mm2, lipid arc with circumferential extension >180°, and the presence of clusters of macrophages) and/or an MLA <2 mm2 are detected by OCT. In the absence of the above-mentioned 4 vulnerability criteria, interventional procedures will be performed at discretion of the operator if a luminal thrombus is detected by OCT. In the physiology-guided arm, non-culprit intermediate lesions will be treated with PCI with implantation of a second-generation DES when an iFR or RFR ≤0.89 or an FFR ≤0.80 are measured, otherwise interventional procedures will be deferred. The primary endpoint, a composite of cardiac death and target vessel spontaneous myocardial infarction, will be assessed after 3 and 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
All events included in the study endpoints will be adjudicated by a blinded Clinical Event Adjudication Committee.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age of at least 18 years.
- •Diagnosis of acute coronary syndrome.
- •Single or multiple intermediate lesions in intervention-naïve major coronary segments (diameter ≥2.5 mm) determining a 40-70% diameter stenosis by visual assessment with no other significant stenosis (>70%) in the same vessel.
- •Patient informed of the nature of the study, agreeing to it, and providing written informed consent as approved by the Ethics Committee of the respective clinical study site.
- •Life expectancy >3 years.
排除标准
- •Female with childbearing potential or lactating.
- •Acute or chronic renal dysfunction (defined as creatinine greater than 2.0 mg/dl).
- •Advanced heart failure (NYHA III-IV)
- •Stroke within the previous 6 months or spontaneous intracranial hemorrhage at any time.
- •Severe valvular disease or valvular disease likely to require surgery or percutaneous valve replacement during the trial.
- •Coronary anatomy preventing complete imaging of the segment of interest (including at least 5 mm at both stenosis edges).
- •Lesions located in the left main coronary artery
- •Diffusely diseased coronary artery segment or presence of ≥1 significant untreated non-culprit lesions (preventing correct adverse event attribution) in the coronary arteries.
- •Prior myocardial infarction or coronary artery bypass graft [CABG] or PCI revascularization in the target coronary vessel.
- •Coronary anatomy unsuitable for PCI.
- •Comorbidities that might interfere with completion of the study procedures.
- •Planned major surgery necessitating interruption of dual antiplatelet.
- •Participating in another investigational drug or device trial that has not completed the primary endpoint or would interfere with the endpoints of this study.
研究组 & 干预措施
Intermediate lesion OCT-based management
At OCT analysis, lesion features prompting intervention instead of conservative approach will be the following:
- FCT <75 µm, plus at least 2 of 3 other OCT criteria of plaque vulnerability (i.e., MLA <3.5 mm2, lipid arc with circumferential extension >180°, and the presence of macrophages).
- The presence of intracoronary thrombus at a non-culprit site, irrespective of the presence of other vulnerability criteria, may prompt treatment with DES, at the operator's discretion.
All lesions fulfilling these interventional criteria will be treated with an OCT guided DES implantation in order to achieve an optimal stent implantation.
In presence of a MLA <2.0 mm2, best cut-off showing correlation with fractional-flow reserve positive functional (FFR) assessment, clinical decision whether to treat the lesion will be based on FFR assessment irrespective of the presence of other criteria of vulnerability. Alternatively authors will have the option to treat the lesion with a DES.
干预措施: Optical coherence tomography (Device)
Intermediate lesion physiology-based management
The iFR/FFR/RFR measurements will be obtained using a coronary-pressure guidewire. For FFR, hyperemia will be induced with the administration of intravenous adenosine, in accordance with the clinical practice at each participating center. Lesion features prompting intervention instead of conservative medical approach will be the following: iFR ≤0.89, or FFR ≤0.80.(32) All lesions fulfilling these interventional criteria will be treated with an FFR guided DES implantation. PCI will be performed with the aim of achieving a post-stenting FFR ≥0.90 (i.e. optimal FFR result). If post-stenting FFR was <0.90 a further post-dilation of the stent could be performed and if FFR remained at <0.90, a pullback of the wire to identify another possible pressure drop and/or a subsequent stent implantation at least 5 mm from the stent will be performed according to physician's preference.
干预措施: iFR/FFR/RFR (Device)
结局指标
主要结局
Number of patients with cardiac death or non-fatal spontaneous target-vessel myocardial infarction
时间窗: 3 years
Composite outcome. Cardiac death will be defined as any death due to heart disease, including heart failure, myocardial infarction, arrhythmia, and sudden unexpected death. Any spontaneous myocardial infarction will be attributed to the randomized intermediate lesion if not clearly attributable to the non-target vessels.
次要结局
- Number of patients with cardiac death(3 years)
- Number of patients with non-fatal spontaneous target-vessel Myocardial infarction (excluding peri-procedural MI)(3 years)
- Number of patients with target lesion revascularization (either percutaneous or surgical)(3 years)
- Number of patients with composite of cardiac death and any myocardial infarction(3 years)
- Number of patients with target vessel failure(3 years)
- Number of patients with composite endpoint of peri-procedural complications(Peri-procedural)
研究者
Francesco Prati
President of Centro per la Lotta Contro l'Infarto - Fondazione Onlus
Centro per la Lotta Contro l'Infarto - Fondazione Onlus