Lithotripsy Versus Balloon Angioplasty for Optimal Treatment of CAlcified Lesions With and Without Optical Coherence Tomography evaluatION
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 3,060
- 试验地点
- 1
- 主要终点
- Target Vessel Failure (TVF) at 3 years
研究概览
简要总结
Severely calcified coronary artery disease means that calcium has built up in the blood vessels that supply the heart. This makes coronary procedures more difficult and increases the risk of complications during and after treatment.
The LOCATION Study is a large clinical study designed to compare different commonly used treatment strategies for patients with severely calcified coronary arteries who need a coronary stent. The study aims to find safer and more effective ways to prepare the artery and place the stent in order to improve long-term outcomes.
In this study, participants will be randomly assigned (like flipping a coin) to one of four treatment groups during their coronary procedure. The treatments differ in two ways: (1) how the calcified artery is prepared before placing the stent, and (2) how imaging is used to guide stent placement.
One method uses a shockwave-based device to help break calcium in the artery, while the other uses standard balloon treatment. For imaging guidance, one approach uses a high-resolution imaging catheter inside the artery, and the other relies on standard X-ray imaging. All participants will receive a standard, approved drug-eluting stent as part of routine care.
The main goal of the study is to determine which treatment approach best reduces serious heart-related problems over three years. These problems include heart-related death, heart attack in the treated vessel, or the need for another procedure on the same vessel.
Adults aged 18 years or older with significant coronary artery narrowing and severe calcium buildup may be eligible to participate. All participants must provide written informed consent before joining the study.
Participants will be followed during their hospital stay and through regular follow-up visits or phone calls for up to three years after the procedure. Information collected during the study will help doctors better understand how to treat patients with severely calcified coronary arteries in the future.
Participation in this study is voluntary, and patients may withdraw at any time without affecting their medical care. All study devices used in this trial are approved for clinical use, and patient privacy will be protected according to applicable regulations.
详细描述
LOCATION Study is a prospective, multicenter, 2x2 factorial randomized controlled trial.
Number of Sites: Approximately 50 sites in China.
Trial Objectives:
Objective 1: To evaluate the efficacy and safety of coronary intravascular lithotripsy (IVL) compared with balloon angioplasty (BA) for pretreatment of severely coronary calcified lesions prior to implantation of stents.
Objective 2: To evaluate the efficacy of optical coherence tomography (OCT)-guided compared with angiography-guided stent implantation in severely coronary calcified lesions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
In addition to the Outcomes Assessor, the following parties are also masked in the clinical trial:
Imaging Core Laboratory Personnel: They perform blinded quantitative analysis on all baseline and post-procedural coronary angiography images, as well as blinded analysis on final OCT images. They are unaware of the subjects' randomized treatment groups to ensure the objectivity of imaging evaluation results.
Clinical Events Committee (CEC) Members: They conduct blinded adjudication of primary and secondary endpoint events (such as target vessel failure, myocardial infarction, etc.). Without knowing the subjects' treatment assignments, they assess the occurrence and severity of events to avoid bias in endpoint judgment.
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
- •Clinical Inclusion criteria:
- •Age ≥18 years;
- •Subject presents with:
- •stable ischemic heart disease or
- •acute coronary syndrome (non-ST-segment elevation myocardial infarction [NSTEMI] or unstable angina), or
- •stabilized recent ST-segment elevation myocardial infarction (STEMI) (>48 hours prior to enrollment);
- •Subject has been fully informed and signed the Institutional Review Board (IRB) approved LOCATION trial Informed Consent Form (ICF) prior to any trial related procedures.
- •Angiographic inclusion criteria：
- •The reference diameter of each target vessel is ≥2.25 mm and ≤4.0 mm at the lesion site (visual estimation);
- •The target lesion(s) have:
- •A stenosis ≥70% and <100% (visual estimation), or
- •A stenosis of the target lesion ≥50% and <70% (visual estimation) with evidence of ischemia via:
- •Positive stress testing (such as single-photon emission computed tomography, echocardiography, treadmill exercise test, etc.), or computed tomography-fractional flow reserve (CT-FFR) value ≤0.80, or;
- •24-hour Holter electrocardiogram: ST-segment elevation or depression of ≥1 mm in horizontal or down-sloping pattern lasting for at least 1 minute, with an interval of more than 1 minute between two episodes; combined with the patient presenting typical angina symptoms with Canadian Cardiovascular Society grading of angina pectoris II - IV;
- •Pressure wire FFR or angioFFR value ≤0.80 or instantaneous wave-free ratio (iFR) value ≤0.
- •3.The target lesion has fluoroscopic evidence of severe calcium at the lesion site, defined via angiogram as fluoroscopic radiopacities noted without cardiac motion before contrast injection involving both sides of the arterial wall in at least 1 location and total length of calcium of at least 15 mm; All lesions in the non-target vessel, if any, that require treatment are successfully treated without complications prior to randomization, defined as final diameter stenosis ≤20% with final TIMI-3 flow, with no residual dissection grade ≥type B, and no transient or sustained angiographic complications (e.g. distal embolization, side branch closure), no chest pain lasting >5 minutes, and no ST-segment elevation or depression lasting >5 minutes.
排除标准
- •Clinical exclusion criteria：
- •Subject has undergone PCI in the target vessel or its branches within 12 months prior to randomization or prior CABG any time;
- •Subject has undergone a PCI procedure in a non-target vessel that is unsuccessful or with complications within 30 days prior to randomization, including during the randomization procedure. Successful and uncomplicated PCI is defined as final diameter stenosis ≤20% with final TIMI-3 flow, no residual dissection grade≥ type B, no transient or sustained angiographic complications (e.g., distal embolization, side branch closure), no chest pain lasting >5 minutes, and no ST-segment elevation or depression lasting >5 minutes);
- •PCI is planned within 12 months post randomization aside from a potential planned staged PCI as part of the randomized treatment strategy;
- •Planned use in the randomized lesion(s) of a bare metal stent (BMS), bioresorbable scaffold (BRS), or non-stent treatment only;
- •The investigator believes that based on the angiographic appearance that 1) it is unlikely that an OCT catheter can be delivered; 2) if randomized to no IVL, it is unlikely that the lesion(s) can be crossed and pre-dilated by balloon angioplasty alone; 3) if randomized to IVL, it is unlikely that the IVL catheter can be delivered to the lesion (note: pre-dilatation is allowed if necessary for IVL delivery);
- •Subject has undergone a prior transcatheter or surgical intervention for a non-coronary cardiac condition (e.g. a TAVR or left atrial appendage occlusion) within the prior 6 months, or is anticipated to need such a procedure within 1 year;
- •Subject has severe stenosis or regurgitation of any heart valve, or moderate aortic stenosis or regurgitation;
- •Subject has evidence of heart failure by at least one of the following:
- •Left ventricular ejection fraction (LVEF) ≤30% within 1 month prior to enrollment, or
- •Current heart failure defined as dyspnea with minimal exertion or at rest (NYHA class III or IV within 1 month of the procedure), or
- •Killip class ≥2 for post STEMI patients; 9.Subject is hemodynamically unstable as evidenced by a SBP of >160 mmHg or <90 mmHg or a heart rate of <50 bpm or >100 bpm (>110 bpm if in atrial fibrillation) 10.Subjects with known allergy to heparin unless bivalirudin will be used as the procedural anticoagulant; 11.Subjects with known allergy to contrast media that cannot be effectively pre-medicated or any prior anaphylaxis to contrast; 12.Subjects with known allergy to aspirin or both clopidogrel and ticagrelor; 13.History of a stroke within 6 months prior to enrollment, excluding transient ischemic attack (TIA) or any prior intracranial bleed; 14.History of active peptic ulcer or upper gastrointestinal bleeding within 6 months prior to enrollment; 15.Inability to tolerate dual antiplatelet therapy for at least 6 months; 16.Known malignancy or any condition with a life expectancy of ≤12 months; 17.Chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m² or on dialysis; 18.Subject has a history of any cognitive or mental health condition that may interfere with the trial participation including all follow-up visits; 19.Subject is a female who is pregnant (women of child-bearing potential must have a negative pregnancy test within 15 days before the procedure); 20.Subject is participating in or has plans to participate in any other investigational drug or device trial that has not reached its primary endpoint.
- •Angiographic Exclusion Criteria:
- •There are no lesions in any target vessel (main epicardial coronary artery including its side branches) that requires treatment that do not meet all angiographic inclusion criteria;
- •A target lesion is an unprotected LM lesion or an ostial lesion (RCA within 3 mm of the aorta proximal LAD or LCX within 3 mm of the LM);
- •A target lesion is a true bifurcation with a severely calcified side branch that requires treatment but cannot be treated with IVL because of its size, angulation or other condition. A severely calcified side branch is defined via angiogram as fluoroscopic radiopacities noted without cardiac motion before contrast injection involving both sides of the arterial wall) Note: If a true bifurcation target lesion is included, the main branch must be severely calcified; the side branch may or may not be severely calcified. However, if the side branch is severely calcified, it must be eligible for IVL treatment. Otherwise, the final treatment for the side branch may be balloon angioplasty, a DCB or a DES as per the judgement of the operator. The main branch must be treated with a DES.
- •A target lesion is totally occluded (100% diameter stenosis with TIMI flow ≤1);
- •A target lesion contains giant thrombus (defined as angiographic length >2x the reference vessel diameter);
- •Presence of an aneurysm within 10 mm of the target lesion;
- •Angiographic evidence of severe dissection (type D - F defined by NHLBI classification) in the target lesion prior to device treatment;
- •A target vessel has severe or excessive tortuosity or is deemed unsuitable for angioplasty by investigator judgement; Any intent to perform intravascular imaging during the randomization procedure (unless randomized to OCT).
研究组 & 干预措施
IVL pre-treatment plus OCT-guided group
(1st OCT) perform OCT after the small balloon pre-dilatation but before the IVL; then IVL is performed* followed by the 1:1 high-pressure balloon pre-dilatation followed by the 2nd OCT; then implant the DES and perform post-dilatation with a high-pressure balloon at ≥18 atm (mandatory); then perform the final OCT (3rd OCT). Assess the stent to determine if further PCI is required to optimize stent implantation - either maximize stent expansion or treat malapposition, tissue protrusion, a major edge dissection or untreated reference segment disease. If further stent optimization is required, do so, after which a final OCT run must be performed again (4th OCT). Note: If IVL is unable to cross or dilate the lesion, rotational atherectomy, orbital atherectomy, or excimer laser should be performed followed by IVL. OCT must still be performed prior to stenting. Investigators should use IVL in accordance with the device's instructions for use.
干预措施: IVL Pretreatment + OCT-Guided Stent Implantation (Device)
IVL pre-treatment plus angiography-guided group
An attempt should be made to cross the target lesion with the IVL catheter after the 1.5 mm or 2.0 mm balloon dilation. If the IVL will not cross the lesion, a larger balloon or atherectomy may be used - then IVL must be performed*. Following successful IVL, pre-dilatation must be performed and be successful (complete balloon expansion) with a high-pressure balloon sized 1:1 to the distal reference segment prior to stenting (mandatory); then one or more stents are implanted (DES only); then post-dilatation must be performed with a high-pressure balloon at ≥18 atm (mandatory). A final OCT run blinded to the operator is then performed as the last procedure. NOTE: Investigators should use IVL in accordance with the device's instructions for use.
干预措施: IVL Pretreatment + Angiography-Guided Stent Implantation (Device)
balloon angioplasty pre-treatment plus OCT-guided group
(1st OCT) perform baseline OCT after the 1.5 or 2.0 mm balloon; then perform balloon pre-dilatation with a high-pressure balloon sized 1:1 to the distal RVD*; then perform OCT again (2nd OCT); then implant the DES and perform post-dilatation with a high-pressure balloon at ≥18 atm (mandatory); then perform the final OCT (3rd OCT). Assess the stent to determine if further PCI is required to optimize stent implantation - either maximize stent expansion or treat malapposition, tissue protrusion, a major edge dissection or untreated reference segment disease. If further stent optimization is required, do so, after which a final OCT run must be performed again (4th OCT).
干预措施: Balloon Angioplasty (BA) Pretreatment + OCT-Guided Stent Implantation (Device)
balloon angioplasty pre-treatment plus angiography-guided group
pre-dilatation must be successful (complete balloon expansion) with a high-pressure balloon (or scoring balloon, cutting balloon, etc.) sized 1:1 to the distal reference segment (mandatory)*; then one or more stents are implanted (DES only); then post-dilatation must be performed with a high-pressure balloon at ≥18 atm (mandatory). *Note: if the 1:1 pre-dilatation balloon is unable to be fully expanded, rotational atherectomy, orbital atherectomy, or excimer laser may be performed. Crossover to IVL is not allowed. After atherectomy or excimer laser, the lesion must again be successfully pre-dilated (complete balloon expansion) with a high-pressure balloon sized 1:1 to the distal reference segment (mandatory) prior to stenting. A final OCT run blinded to the operator is then performed as the last procedure;
干预措施: Balloon Angioplasty (BA) Pretreatment + Angiography-Guided Stent Implantation (Device)
结局指标
主要结局
Target Vessel Failure (TVF) at 3 years
时间窗: 3 years
Composite time-to-first event rate of cardiac death, target vessel myocardial infarction (TV-MI), or ischemia-driven target vessel revascularization (iTVR) at 3 years, assessed when the last enrolled patient reaches 1-year follow-up
次要结局
- Target Lesion Failure (TLF)(30 days, 6 months ,1 year, 2 years, and 3 years)
- Major Adverse Cardiovascular Events (MACE)(30 days, 6 months,1 year, 2 years, and 3 years)
- Major Adverse Cardiovascular and Cerebrovascular Events (MACCE)(30 days, 6 months,1 year, 2 years, and 3 years)
- Cardiac death(30 days, 6 months,1 year, 2 years, and 3 years)
- Incidence of stent thrombosis(30 days, 6 months,1 year, 2 years, and 3 years)
- Severe angiographic complications(Immediate post-procedure)
- Procedural strategy success(Immediate post-procedure)
- Post-procedural minimum stent area (MSA) at the site of maximum calcification and across the entire target lesion;(Immediate post-procedure)
- Post-procedural mean stent area(Immediate post-procedure)
- Post-procedural minimum lumen diameter (MLD)(Immediate post-procedure)
- Minimum stent expansion(Immediate post-procedure)
- Stent malposition(Immediate post-procedure)
- Number of calcification fractures(Immediate post-procedure)
- Major and minor edge dissection(Immediate post-procedure)
- Major and minor tissue protrusion(Immediate post-procedure)
- Incidence of Untreated reference segment disease(Immediate post-procedure)
- Target vessel myocardial infarction (TV-MI)(30 days, 6 months,1 year, 2 years, and 3 years)
- ischemia-driven target vessel revascularization (iTVR)(30 days, 6 months,1 year, 2 years, and 3 years)
- all-cause death(30 days, 6 months,1 year, 2 years, and 3 years)
- Stoke(30 days, 6 months,1 year, 2 years, and 3 years)
- any revascularization(30 days, 6 months,1 year, 2 years, and 3 years)
- Post-procedural mean lumen diameter(LD)(Immediate post-procedure)
- Mean stent expansion(Immediate post-procedure)
- Thickness (full-layer or partial) of calcification （mm)(Immediate post-procedure)
- Depth of calcification fractures(mm）(Immediate post-procedure)
- TVF （Target Vessel Failure ）(at 1 and 2 years)(1 and 2 years)
- MI （Myocardial Infarction）(30 days, 6 months,1 year, 2 years, and 3 years)