Lithotripsy Versus Balloon Angioplasty for Optimal Treatment of CAlcified Lesions With and Without Optical Coherence Tomography evaluatION

NCT07388030 | Not Yet Recruiting DMC

• 1 other identifier: LFBY-202504
• Study Type: interventional
• Target: 3,060
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Artery Disease; Severe Coronary Artery Disease; Coronary Artery Calcification

Keywords

severe coronary calcified lesions; intravascular lithotripsy (IVL); balloon angioplasty (BA); optical coherence tomography (OCT)-guided; angiography-guided; target vessel failure (TVF); percutaneous coronary intervention (PCI)

Outcome Measures

Primary Outcomes (1)

• Target Vessel Failure (TVF) at 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

  3 years

Secondary Outcomes (27)

• TVF （Target Vessel Failure ）(at 1 and 2 years)

  1 and 2 years

• 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

Study Arms (4)

IVL pre-treatment plus OCT-guided group

EXPERIMENTAL

(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.

Device: IVL Pretreatment + OCT-Guided Stent Implantation

IVL pre-treatment plus angiography-guided group

ACTIVE COMPARATOR

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.

Device: IVL Pretreatment + Angiography-Guided Stent Implantation

balloon angioplasty pre-treatment plus OCT-guided group

ACTIVE COMPARATOR

(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).

Device: Balloon Angioplasty (BA) Pretreatment + OCT-Guided Stent Implantation

balloon angioplasty pre-treatment plus angiography-guided group

ACTIVE COMPARATOR

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;

Device: Balloon Angioplasty (BA) Pretreatment + Angiography-Guided Stent Implantation

Interventions

IVL Pretreatment + OCT-Guided Stent Implantation DEVICE

Subjects who have signed ICF and have met all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 to IVL vessel preparation strategy or balloon angioplasty vessel preparation strategy. Concurrently, subjects will randomly be assigned in a 1:1 ratio to receive OCT-guidance or angiographic-guidance of the PCI procedure. Subject randomization in each of the 4 groups will be stratified by site and diabetes in varying block sizes of 2, 4 or 6. Randomization will be conducted with the use of an interactive web response system (IWRS).

IVL pre-treatment plus OCT-guided group

IVL Pretreatment + Angiography-Guided Stent Implantation DEVICE

Subjects who have signed ICF and have met all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 to IVL vessel preparation strategy or balloon angioplasty vessel preparation strategy. Concurrently, subjects will randomly be assigned in a 1:1 ratio to receive OCT-guidance or angiographic-guidance of the PCI procedure. Subject randomization in each of the 4 groups will be stratified by site and diabetes in varying block sizes of 2, 4 or 6. Randomization will be conducted with the use of an interactive web response system (IWRS).

IVL pre-treatment plus angiography-guided group

Balloon Angioplasty (BA) Pretreatment + OCT-Guided Stent Implantation DEVICE

Subjects who have signed ICF and have met all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 to IVL vessel preparation strategy or balloon angioplasty vessel preparation strategy. Concurrently, subjects will randomly be assigned in a 1:1 ratio to receive OCT-guidance or angiographic-guidance of the PCI procedure. Subject randomization in each of the 4 groups will be stratified by site and diabetes in varying block sizes of 2, 4 or 6. Randomization will be conducted with the use of an interactive web response system (IWRS).

balloon angioplasty pre-treatment plus OCT-guided group

Balloon Angioplasty (BA) Pretreatment + Angiography-Guided Stent Implantation DEVICE

Subjects who have signed ICF and have met all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 to IVL vessel preparation strategy or balloon angioplasty vessel preparation strategy. Concurrently, subjects will randomly be assigned in a 1:1 ratio to receive OCT-guidance or angiographic-guidance of the PCI procedure. Subject randomization in each of the 4 groups will be stratified by site and diabetes in varying block sizes of 2, 4 or 6. Randomization will be conducted with the use of an interactive web response system (IWRS).

balloon angioplasty pre-treatment plus angiography-guided group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:
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• 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;
• 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 ≤0.89.
• 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.

You may not qualify if:

• 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.
• 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);

Sponsors & Collaborators

• Shanghai Bluesail Boyuan Medical Technology Co., Ltd.: lead

Study Sites (1)

General Hospital of Northern Theater Command

Shenyang, Liaoning, 110011, China

Location

Related Publications (16)

• [16] Han Y, Jing Q, Liu H, et al. A novel coronary intravascular Lithotripsy device in patients with severely calcified lesions: LEAD-FIM study. Presented at EuroPCR 2024.

  RESULT

• [15] Kirtane AJ, Généreux P, Lewis B, Shlofmitz RA, Dohad S, Choudary J, Dahle T, Pineda AM, Shunk K, Maehara A, Popma A, Redfors B, Ali ZA, Krucoff M, Armstrong E, Kandzari DE, O'Neill W, Kraemer C, Stiefel KM, Jones DE, Chambers J, Stone GW; ECLIPSE Investigators. Orbital atherectomy versus balloon angioplasty before drug-eluting stent implantation in severely calcified lesions eligible for both treatment strategies (ECLIPSE): a multicentre, open-label, randomised trial. Lancet. 2025 Apr 12;405(10486):1240-1251.

  RESULT

• [14] Moussa ID, Klein LW, Shah B et al. Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Journal Pre-proof Society for Cardiovascular Angiography and Interventions (SCAI). J Am Coll Cardiol. 2013; 62:1563-70

  RESULT

• [13] Blachutzik F, Meier S, Weissner M, et al. Comparison of coronary intravascular lithotripsy and rotational atherectomy in the modification of severely calcified stenosis[J]. Am J Cardiol,2023,197: 93-100. DOI: 10.1016/j.amjcard.2023.02.028.

  RESULT

• [12] Mousa MAA, Bingen BO, Al Amri I, et al. Efficacy and safety of intravascular lithotripsy versus rotational atherectomy in balloon-crossable heavily calcified coronary lesions [J]. Cardiovasc Revasc Med, 2023,48: 1-6.

  RESULT

• [11] Cubero-Gallego H, Calvo-Fernandez A, Tizon-Marcos H, et al. Real-world multicenter coronary lithotripsy registry: long-term clinical follow-up[J]. J Invasive Cardiol, 2022, 34(10)：E701-E708.

  RESULT

• [10] Wong B， El-Jack S， Newcombe R， et al. Shockwave intravascular lithotripsy for calcified coronary lesions： first real-world experience[J]. J Invasive Cardiol, 2019, 31(3):46-48.

  RESULT

• [9] Rodriguez-Leor, O, Cid-Alvarez, A, Lopez-Benito, M. et al. A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries: The REPLICA-EPIC18 Study. J Am Coll Cardiol Intv. 2024 Mar, 17 (6) 756-767.

  RESULT

• [8] Tian F， Zhou SS， Liu JH， et al. Treatment of severely calcified coronary artery disease by intravascular lithotripsy primary outcomes and 180-day follow-up from the Chinese SOLSTICE Trial [J]. J Geriatr Cardiol， 2023, 20(1)： 32-39. DOI：10.26599/1671-5411.2023.01.005.

  RESULT

• [7] Hill JM, Kereiakes DJ, Shlofmitz RA, Klein AJ, Riley RF, Price MJ, Herrmann HC, Bachinsky W, Waksman R, Stone GW; Disrupt CAD III Investigators. Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease. J Am Coll Cardiol. 2020 Dec 1;76(22):2635-2646.

  RESULT

• [6] Saito S, Yamazaki S, Takahashi A, et al. Intravascular Lithotripsy for Vessel Preparation in Severely Calcified Coronary Arteries Prior to Stent Placement - Primary Outcomes from the Japanese Disrupt CAD IV Study. Circ J.2021 May 25;85(6):826-833.

  RESULT

• Kereiakes DJ, Hill JM, Ben-Yehuda O, Maehara A, Alexander B, Stone GW. Evaluation of safety and efficacy of coronary intravascular lithotripsy for treatment of severely calcified coronary stenoses: Design and rationale for the Disrupt CAD III trial. Am Heart J. 2020 Jul; 225:10-18. doi: 10.1016/j.ahj.2020.04.005.

  RESULT

• Hill JM, Kereiakes DJ, et al. Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease. J Am Coll Cardiol. 2020 Dec 1;76(22):2635-2646. doi: 10.1016/j.jacc.2020.09.603.

  RESULT

• Ali ZA, Nef H, et al. Safety and Effectiveness of Coronary Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Stenoses: The Disrupt CAD II Study. Circ Cardiovasc Interv. 2019 Oct;12(10): e008434.

  RESULT

• Brinton TJ, et al. Feasibility of Shockwave Coronary Intravascular Lithotripsy for the Treatment of Calcified Coronary Stenoses. Circulation. 2019 Feb 5;139(6):834-836.

  RESULT

• Chinese Society of Cardiology, Chinese Medical Association; Editorial Board of Chinese Journal of Cardiology. Guidelines for percutaneous coronary intervention (2025). Zhonghua Xin Xue Guan Bing Za Zhi. 2025 Jun 12; 53:16-44. Chinese. doi: 10.3760/cma.j.cn112148-20250422-00302. Epub ahead of print.

  RESULT

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Angioplasty, Balloon

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Angioplasty; Catheterization; Therapeutics; Endovascular Procedures; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Investigative Techniques

Study Officials

• Yaling Han

  The General Hospital of Northern Theater Command

  PRINCIPAL INVESTIGATOR

• Gregg W. Stone

  Icahn School of Medicine at Mount Sinai, USA

  STUDY CHAIR

Central Study Contacts

Yuanchun Sun

CONTACT

+8613683382436; yuc.sun@jwmsgrp.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The LOCATION study adopts a \*\*prospective, multicenter, 2×2 factorial randomized controlled model\*\* for severe coronary calcified lesions. Key details: 1. \*\*Randomization\*\*: 3,060 patients are 1:1 randomized to IVL/BA pretreatment and 1:1 to OCT/angiography guidance (4 parallel groups), stratified by site and diabetes with block sizes 2/4/6 via IWRS. 2. \*\*Interventions\*\*: IVL (SoniCracker™) vs standard BA for lesion prep; OCT (Nanjing Forssmann) vs angiography for stent guidance. 3. \*\*Crossover Rules\*\*: BA→IVL prohibited; IVL→other devices allowed only for specific criteria (recorded as failure). 4. \*\*Blinding\*\*: Open-label for investigators/subjects; core lab and CEC adjudicate outcomes blindly. 5. \*\*Follow-up\*\*: 30 days, 6 months, 1/2/3 years + sweep visit; primary endpoint is 3-year TVF. 6. \*\*Analysis Sets\*\*: ITT (efficacy), PP (sensitivity), SS (safety).

Study Record Dates

• First Submitted: January 15, 2026
• First Posted: February 4, 2026
• Study Start: March 20, 2026
• Primary Completion (Estimated): January 20, 2030
• Study Completion (Estimated): June 30, 2030
• Last Updated: March 12, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)