Clinical trial NCT04151628: Disrupt CAD IV With the Shockwave Coronary IVL System
Official title: Prospective, Multicenter, Single-Arm Study of the SWM-1234 in Calcified Coronary Arteries (Disrupt CAD IV Study - Japan)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Myocardial Infarction
Keywords: Intravascular Lithotripsy
Percutaneous Coronary Intervention
Lead sponsor: Shockwave Medical, Inc.
Sponsor class: INDUSTRY
First posted: 2019-11-05
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The Coronary IVL System is a proprietary balloon catheter system designed to enhance stent outcomes by enabling delivering of the calcium disrupting capability of lithotripsy prior to balloon dilatation at low pressures. The Coronary IVL System consists of an IVL Balloon Catheter with 2 integrated emitters, a Lithotripsy Generator, and a Connector Cable.
Primary purpose: TREATMENT

Brief summary: The study design is a prospective, multicenter, single-arm study to evaluate the safety and effectiveness of the Shockwave Medical Coronary Intravascular Lithotripsy (IVL) System in de novo, calcified, stenotic coronary arteries prior to stenting.

Detailed description: Subject Population: Subjects ≥ 18 years of age with de novo, calcified coronary artery lesions presenting with stable, unstable or silent ischemia that are suitable for percutaneous coronary intervention. Approximately 72 subjects at 8 sites in Japan will be enrolled. Subjects will be followed through discharge, 30 days, 6, 12 and 24 months.

Eligibility criteria: Inclusion Criteria:

1. Subject is ≥18 years of age
2. Subjects with native coronary artery disease (including stable or unstable angina and silent ischemia) suitable for PCI
3. For patients with unstable ischemic heart disease, biomarkers (troponin or CK-MB) must be less than or equal to the upper limit of lab normal within 12 hours prior to the procedure (note: if both labs are drawn both must be normal)
4. For patients with stable ischemic heart disease, biomarkers may be drawn prior to the procedure or at the time of the procedure from the side port of the sheath.

   1. If drawn prior to the procedure, biomarkers (troponin or CK- MB) must be less than or equal to the upper limit of lab normal within 12 hours prior to the index procedure (note: if both labs are drawn, both must be normal)
   2. If biomarkers are drawn at the time of the procedure from the side port of the sheath prior to any intervention, biomarker results do not need to be analyzed prior to enrollment.
5. Left ventricular ejection fraction \> 25% within 6 months (note: in the case of multiple assessments of LVEF, the measurement closest to enrollment will be used for this criteria; may be assessed at time of index procedure)
6. Subject or legally authorized representative, signs a written Informed Consent form to participate in the study, prior to any study-mandated procedures
7. Lesions in non-target vessels requiring PCI may be treated either:

   1. \>30 days prior to the study procedure if the procedure was unsuccessful or complicated; or
   2. \>24 hours prior to the study procedure if the procedure was successful and uncomplicated (defined as a final lesion angiographic diameter stenosis \<30% and TIMI 3 flow (visually assessed) for all non-target lesions and vessels without perforation, cardiac arrest or need for defibrillation or cardioversion or hypotension/heart failure requiring mechanical or intravenous hemodynamic support or intubation, and with no post-procedure biomarker elevation

      \>normal; or
   3. \>30 days after the study procedure

   Angiographic Inclusion Criteria
8. The target lesion must be a de novo coronary lesion that has not been previously treated with any interventional procedure
9. Single de novo target lesion stenosis of protected LMCA, or LAD, RCA or LCX (or of their branches) with:

   1. Stenosis of ≥70% and \<100% or
   2. Stenosis ≥50% and \<70% (visually assessed) with evidence of ischemia via positive stress test, or fractional flow reserve value ≤0.80, or iFR \<0.90 or IVUS or OCT minimum lumen area ≤4.0 mm²
10. The target vessel reference diameter must be ≥2.5 mm and ≤4.0 mm
11. The lesion length must not exceed 40 mm
12. The target vessel must have TIMI flow 3 at baseline (visually assessed, may be assessed after pre-dilatation)
13. Evidence of calcification at the lesion site by, a) angiography, with fluoroscopic radio-opacities noted without cardiac motion prior to contrast injection involving both sides of the arterial wall in at least one location and total length of calcium of at least 15 mm and extending partially into the target lesion, OR by b) IVUS or OCT, with presence of ≥270 degrees of calcium on at least 1 cross section
14. Ability to pass a 0.014" guide wire across the lesion

Exclusion Criteria:

1. Any comorbidity or condition which may reduce compliance with this protocol, including follow-up visits
2. Subject is a member of a vulnerable population including individuals with mental disability, persons in nursing homes, children, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those incapable of giving informed consent.
3. Subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached the primary endpoint
4. Subject is pregnant or nursing (a negative pregnancy test is required for women of child-bearing potential within 7 days prior to enrollment)
5. Unable to tolerate dual antiplatelet therapy (i.e., aspirin, and either clopidogrel, prasugrel, or ticagrelor) for at least 6 months
6. Subject has an allergy to imaging contrast media which cannot be adequately pre-medicated
7. Subject experienced an acute MI (STEMI or non-STEMI) within 30 days prior to index procedure, defined as a clinical syndrome consistent with an acute coronary syndrome with troponin or CK- MB greater than 1 times the local laboratory's upper limit of normal
8. New York Heart Association (NYHA) class III or IV heart failure
9. Renal failure with serum creatinine \>2.5 mg/dL, or chronic dialysis
10. History of a stroke or transient ischemic attack (TIA) within 6 months, or any prior intracranial hemorrhage or permanent neurologic deficit
11. Active peptic ulcer or upper gastrointestinal (GI) b≥leeding within 6 months
12. Untreated pre-procedural hemoglobin \<10 g/dL or intention to refuse blood transfusions if one should become necessary
13. Coagulopathy, including but not limited to platelet count \<100,000 or International Normalized ratio (INR) \>1.7 (INR is only required in subjects who have taken warfarin within 2 weeks of enrollment)
14. Subject has a hypercoagulable disorder such as polycythemia vera, platelet count \>750,000 or other disorders
15. Uncontrolled diabetes defined as a HbA1c ≥10%
16. Subject has an active systemic infection on the day of the index procedure with either fever, leukocytosis or requiring intravenous antibiotics
17. Subjects in cardiogenic shock or with clinical evidence of left-sided heart failure (S3 gallop, pulmonary rales, oliguria, or hypoxemia)
18. Uncontrolled severe hypertension (systolic BP \>180 mm Hg or diastolic BP \>110 mm Hg)
19. Subjects with a life expectancy of less than 1 year
20. Non-coronary interventional (e.g., TAVR, MitraClip, or PFO occlusion, etc.) or surgical structural heart procedures within 30 days prior to the index procedure
21. Planned non-coronary interventional (e.g., TAVR, MitraClip, or PFO occlusion, etc.) or surgical structural heart procedures within 30 days after the index procedure
22. Subject refusing or not a candidate for emergency coronary artery bypass grafting (CABG) surgery
23. Planned use of atherectomy, scoring or cutting balloon, or any investigational device other than lithotripsy
24. Unprotected left main diameter stenosis \>30%
25. Target vessel is excessively tortuous defined as the presence of two or more bends \>90º or three or more bends \>75º
26. Definite or possible thrombus (by angiography or intravascular imaging) in the target vessel
27. Evidence of aneurysm in target vessel within 10 mm of the target lesion
28. Target lesion is an ostial location (LAD, LCX, or RCA, within 5 mm of ostium) or an unprotected left main lesion
29. Target lesion is a bifurcation with ostial diameter stenosis ≥30%
30. Second lesion with \>50% stenosis in the same target vessel as the target lesion including its side branches
31. Target lesion is located in a native vessel that can only be reached by going through a saphenous vein or arterial bypass graft
32. Previous stent within the target vessel implanted within the last year
33. Previous stent within 10 mm of the target lesion regardless of the timing of its implantation
34. Angiographic evidence of a dissection in the target vessel at baseline or after guidewire passage

Primary outcomes:
measure: Percentage of Participants Who Experienced Freedom From MACE Within 30 Days Post-procedure
timeFrame: Within 30 days of index procedure
measure: Percentage of Subjects With Procedural Success
timeFrame: 12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure
Secondary outcomes:
measure: Number of Participants With Device Crossing Success
timeFrame: At end of procedure, with a mean total procedure time of 62.5 minutes
measure: Number of Participants With Angiographic Success (Residual Stenosis <50%)
timeFrame: At end of procedure, with a mean total procedure time of 62.5 minutes
measure: Number of Participants With Procedural Success (Residual Stenosis <=30%)
timeFrame: 12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure
measure: Number of Participants With Angiographic Success (Residual Stenosis <=30%)
timeFrame: At end of procedure, with a mean total procedure time of 62.5 minutes
measure: Number of Participants With Serious Angiographic Complications
timeFrame: At end of procedure, with a mean total procedure time of 62.5 minutes
measure: MACE Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: MACE Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: MACE Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Target Lesion Failure (TLF) at 30 Days
timeFrame: Within 30 days of index procedure
measure: Target Lesion Failure (TLF) at 6 Months
timeFrame: Within 6 months of index procedure
measure: Target Lesion Failure (TLF) at 12 Months
timeFrame: Within 12 months of index procedure
measure: Target Lesion Failure (TLF) at 24 Months
timeFrame: Within 24 months of index procedure
measure: All-Cause Death at 30 Days
timeFrame: Within 30 days from index procedure
measure: All-Cause Death at 6 Months
timeFrame: within 6 months of index procedure
measure: All-Cause Death at 12 Months
timeFrame: within 12 months of procedure
measure: All-Cause Death at 24 Months
timeFrame: within 24 months of procedure
measure: Myocardial Infarction (MI) at 30 Days
timeFrame: within 30 days of index procedure
measure: Myocardial Infarction (MI) at 6 Months
timeFrame: Within 6 months of index procedure
measure: Myocardial Infarction (MI) at 12 Months
timeFrame: Within 12 months of index procedure
measure: Myocardial Infarction (MI) at 24 Months
timeFrame: Within 24 months of index procedure
measure: Myocardial Infarction Attributable to Target Vessel (TV-MI) at 30 Days
timeFrame: within 30 days of index procedure
measure: Myocardial Infarction Attributable to Target Vessel (TV-MI) at 6 Months
timeFrame: Within 6 month of index procedure
measure: Myocardial Infarction Attributable to Target Vessel (TV-MI) at 12 Months
timeFrame: Within 12 months of index procedure
measure: Myocardial Infarction Attributable to Target Vessel (TV-MI) at 24 Months
timeFrame: Within 24 months of index procedure
measure: Stent Thrombosis at 30 Days
timeFrame: Within 30 days of index procedure
measure: Stent Thrombosis at 6 Months
timeFrame: within 6 months of index procedure
measure: Stent Thrombosis at 12 Months
timeFrame: within 12 months of index procedure
measure: Stent Thrombosis at 24 Months
timeFrame: within 24 months of index procedure
measure: All Revascularizations at 30 Days
timeFrame: within 30 days of index procedure
measure: All Revascularizations at 6 Months
timeFrame: within 6 months of index procedure
measure: All Revascularizations at 12 Months
timeFrame: within 12 months of index procedure
measure: All Revascularizations at 24 Months
timeFrame: within 24 months of index procedure
measure: Ischemia-Driven Target Vessel Revascularization (ID-TVR) at 30 Days
timeFrame: within 30 days of index procedure
measure: Ischemia-Driven Target Vessel Revascularization (ID-TVR) at 6 Months
timeFrame: within 6 months of index procedure
measure: Ischemia-driven Target Vessel Revascularization (ID-TVR) at 12 Months
timeFrame: within 12 months of index procedure
measure: Ischemia-driven Target Vessel Revascularization (ID-TVR) at 24 Months
timeFrame: within 24 months of index procedure
measure: Ischemia-Driven Target Lesion Revascularization (ID-TLR) at 30 Days
timeFrame: within 30 days of index procedure
measure: Ischemia-Driven Target Lesion Revascularization (ID-TLR) at 6 Months
timeFrame: within 6 months of index procedure
measure: Ischemia-Driven Target Lesion Revascularization (ID-TLR) at 12 Months
timeFrame: within 12 months of index procedure
measure: Ischemia-Driven Target Lesion Revascularization (ID-TLR) at 24 Months
timeFrame: within 24 months of index procedure
measure: Non-Ischemia-Driven Target Vessel Revascularization (Non-ID-TVR) at 30 Days
timeFrame: within 30 days of index procedure
measure: Non-Ischemia-Driven Target Vessel Revascularization (Non-ID-TVR) at 6 Months
timeFrame: within 6 months of index procedure
measure: Non-Ischemia-Driven Target Vessel Revascularization (Non-ID-TVR) at 12 Months
timeFrame: within 12 months of index procedure
measure: Non-Ischemia-Driven Target Vessel Revascularization (Non-ID-TVR) at 24 Months
timeFrame: within 24 months of index procedure
measure: Non-Ischemia-Driven Target Lesion Revascularization (Non-ID-TLR) at 30 Days
timeFrame: within 30 days of index procedure
measure: Non-Ischemia-Driven Target Lesion Revascularization (Non-ID-TLR) at 6 Months
timeFrame: within 6 months of index procedure
measure: Non-Ischemia-Driven Target Lesion Revascularization (Non-ID-TLR) at 12 Months
timeFrame: within 12 months of index procedure
measure: Non-Ischemia-Driven Target Lesion Revascularization (Non-ID-TLR) at 24 Months
timeFrame: within 24 months of index procedure
measure: Procedural MI at 30 Days
timeFrame: within 30 days of index procedure
measure: Procedural MI at 6 Months
timeFrame: within 6 months of index procedure
measure: Procedural MI at 12 Months
timeFrame: within 12 months of index procedure
measure: Procedural MI at 24 Months
timeFrame: within 24 months of index procedure
measure: Non-Procedural MI at 30 Days
timeFrame: within 30 days of index procedure
measure: Non-Procedural MI at 6 Months
timeFrame: within 6 months of index procedure
measure: Non-Procedural MI at 12 Months
timeFrame: within 12 months of index procedure
measure: Non-Procedural MI at 24 Months
timeFrame: within 24 months of index procedure
measure: Myocardial Infarction (MI) Using the Fourth Universal Definition of MI, at 30 Days
timeFrame: within 30 days of index procedure
measure: Myocardial Infarction (MI) Using the Fourth Universal Definition of MI, at 6 Months
timeFrame: within 6 months of index procedure
measure: Myocardial Infarction (MI) Using the Fourth Universal Definition of MI, at 12 Months
timeFrame: within 12 months of index procedure
measure: Myocardial Infarction (MI) Using the Fourth Universal Definition of MI, at 24 Months
timeFrame: within 24 months of index procedure
measure: Myocardial Infarction (MI) Using the Society for Cardiovascular Angiography and Interventions (SCAI) Definition, at 30 Days
timeFrame: within 30 days of index procedure
measure: Myocardial Infarction (MI) Using the Society for Cardiovascular Angiography and Interventions (SCAI) Definition, at 6 Months
timeFrame: within 6 months of index procedure
measure: Myocardial Infarction (MI) Using the Society for Cardiovascular Angiography and Interventions (SCAI) Definition, at 12 Months
timeFrame: within 12 months of index procedure
measure: Myocardial Infarction (MI) Using the Society for Cardiovascular Angiography and Interventions (SCAI) Definition, at 24 Months
timeFrame: within 24 months of index procedure
Other outcomes:
Locations:
city: Kurume
country: Japan
facility: Tenjinkai Shin-Koga Hospital
state: Fukuoka-Ken
city: Sapporo
country: Japan
facility: Sapporo Higashi Tokushukai Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Sakurakai Takahashi Hospital
state: Hyogo-Ken
city: Takarazuka
country: Japan
facility: Higashi-Takarazuka Satoh Hospital
state: Hyogo-Ken
city: Kawasaki
country: Japan
facility: Johas Kanto Rosai Hospital
state: Kanagawa-Ken
city: Kamakura
country: Japan
facility: Shonan-Kamakura General Hospital
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: Kyoto-Katsura Hospital
state: Kyoto-Fu
city: Miyazaki
country: Japan
facility: Miyazaki Medical Association Hospital
state: Miyazaki-Ken
Study officials:
affiliation: Columbia University
name: Gregg W Stone, MD
role: STUDY_CHAIR
affiliation: Shonan Kamakura General Hospital
name: Shigeru Saito, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Saito S, Yamazaki S, Takahashi A, Namiki A, Kawasaki T, Otsuji S, Nakamura S, Shibata Y; Disrupt CAD IV Investigators. 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. doi: 10.1253/circj.CJ-20-1174. Epub 2021 Feb 5.
citation: Kereiakes DJ, Di Mario C, Riley RF, Fajadet J, Shlofmitz RA, Saito S, Ali ZA, Klein AJ, Price MJ, Hill JM, Stone GW. Intravascular Lithotripsy for Treatment of Calcified Coronary Lesions: Patient-Level Pooled Analysis of the Disrupt CAD Studies. JACC Cardiovasc Interv. 2021 Jun 28;14(12):1337-1348. doi: 10.1016/j.jcin.2021.04.015. Epub 2021 May 3.