Shockwave Coronary Lithoplasty® Study (Disrupt CAD II)

• ClinicalTrials.gov Identifier: NCT03328949
• Recruitment Status: Completed
• First Posted: November 1, 2017
• Last Update Posted: June 20, 2019
• Sponsor: Shockwave Medical, Inc.
• Information provided by (Responsible Party): Shockwave Medical, Inc.

Tracking Information

• First Submitted Date: October 27, 2017
• First Posted Date: November 1, 2017
• Last Update Posted Date: June 20, 2019
• Actual Study Start Date: May 18, 2018
• Actual Primary Completion Date: March 26, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 30, 2017)

In-hospital major adverse cardiac events (MACE) [ Time Frame: 1 day post-procedure ]

The primary safety endpoint is the frequency of in-hospital major adverse cardiac events (MACE). MACE is defined as the following:

• Cardiac death
• MI - defined as a CK-MB level > 3 times the upper limit of lab normal (ULN) value with or without new pathologic Q wave
• TVR - defined as revascularization at the target vessel (inclusive of the target lesion) after the completion of the index procedure

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03328949 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: April 26, 2018)

• Residual stenosis (<50%) after stenting [ Time Frame: Procedural ]
  Performance will be assessed by the ability of the Lithotripsy System to produce acceptable residual stenosis (<50%) after stenting with no evidence of in-hospital MACE. Each patient that achieves both of these requirements will be considered a "clinical success", and the rate of clinical success among subjects will be evaluated.
• Angiographic success [ Time Frame: Procedural ]
  Angiographic success defined as success in facilitating stent delivery with <50% residual stenosis and without serious angiographic complications. Serious angiographic complications defined as severe dissection (Type D to F), perforation, abrupt closure, and persistent slow flow or persistent no reflow.
• Cardiac Death [ Time Frame: 30 days ]
  Cardiac death at 30 days.

Original Secondary Outcome Measures (submitted: October 30, 2017)

• Residual stenosis (<50%) after stenting [ Time Frame: Procedural ]
  Performance will be assessed by the ability of the Lithoplasty System to produce acceptable residual stenosis (<50%) after stenting with no evidence of in-hospital MACE. Each patient that achieves both of these requirements will be considered a "clinical success", and the rate of clinical success among subjects will be evaluated.
• Angiographic success [ Time Frame: Procedural ]
  Angiographic success defined as success in facilitating stent delivery with <50% residual stenosis and without serious angiographic complications. Serious angiographic complications defined as severe dissection (Type D to F), perforation, abrupt closure, and persistent slow flow or persistent no reflow.
• Cardiac Death [ Time Frame: 30 days ]
  Cardiac death at 30 days.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Shockwave Coronary Lithoplasty® Study (Disrupt CAD II)
• Official Title: Prospective Multi-Center, Single Arm Post-Market Study (PMS) of the Shockwave Medical, Inc. Coronary Lithoplasty® System in Coronary Arteries
• Brief Summary: The objective of this post market study is to examine the safety and performance of the Shockwave Coronary Intravascular Lithotripsy System for the treatment of narrowed coronary arteries before the doctor places a stent.

Detailed Description

The study will be conducted at 15 sites in Europe and up to 120 participants will be followed for 30 days post procedure.

Patients ≥18 years of age scheduled for stent procedure with evidence of significant calcified stenosis of left main, or left anterior descending, right coronary artery or left circumflex will be eligible to enroll in the study. The primary endpoint of the study will evaluate major adverse cardiac events post procedure including 1) cardiac related death, 2) heart attack, and 3) intervention to treat the coronary artery that was previously treated at the procedure visit.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Intervention Model: Single Group Assignment
Intervention Model Description:

Intravascular Coronary Lithotripsy System

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Coronary Artery Disease

Intervention

Device: IVL Coronary Lithotripsy System

The coronary intravascular lithotripsy catheter is similar to other balloon devices that are routinely used during angioplasty procedures; however, it has electrodes inside the balloon which are designed to deliver energy to crack the calcified blockage using lithotripsy (acoustic energy).

Study Arms

Experimental: IVL Coronary Lithotripsy System

All enrolled patients will receive treatment from the IVL coronary lithotripsy system prior to coronary stent placement.

Intervention: Device: IVL Coronary Lithotripsy System

• Publications *: Ali ZA, Nef H, Escaned J, Werner N, Banning AP, Hill JM, De Bruyne B, Montorfano M, Lefevre T, Stone GW, Crowley A, Matsumura M, Maehara A, Lansky AJ, Fajadet J, Di Mario C. 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. doi: 10.1161/CIRCINTERVENTIONS.119.008434. Epub 2019 Sep 25.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 30, 2017): 120
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 25, 2019
• Actual Primary Completion Date: March 26, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patient is ≥ 18 years of age
2. Troponin must be less than or equal to the upper limit of lab normal value within 24 hours prior to the procedure OR if troponin is elevated, concomitant CK must be normal
3. The target vessel must have a TIMI flow 3 at baseline
4. Patients with significant (≥ 50% diameter stenosis) native coronary artery disease including stable or unstable angina and silent ischemia, suitable for PCI
5. Ability to tolerate dual antiplatelet agent (i.e. aspirin, clopidogrel, prasugrel, or ticagrelor) for 1 year and single antiplatelet therapy for life
6. Single lesion stenosis of protected LMCA, or LAD, RCA or LCX artery ≥50% in a reference vessel of 2.5 mm - 4.0 mm diameter and ≤ 32 mm length
7. Presence of calcification within the lesion on both sides of the vessel as assessed by angiography
8. Planned treatment of single lesion in one vessel
9. Ability to pass a 0.014" guide wire across the lesion
10. Patient, or authorized representative, signs a written Informed Consent form to participate in the study, prior to any study-mandated procedures
11. Patient is able and willing to comply with all assessments in the study

Exclusion Criteria:

1. Concomitant use of Atherectomy, Specialty balloon, or investigational coronary devices
2. Prior PCI procedure within the last 30 days of the index procedure
3. Patient has planned cardiovascular interventions within 30 days post index procedure
4. Second lesion with ≥50% stenosis in the same target vessel
5. Left ventricular ejection fraction < 40%
6. Patient refusing or not a candidate for emergency coronary artery bypass grafting (CABG) surgery
7. Uncontrolled severe hypertension (systolic BP >180 mm Hg or diastolic BP >110 mm Hg)
8. Severe renal failure with serum creatinine >2.5 mg/dL, unless on chronic dialysis
9. Untreated pre-procedural hemoglobin <10 g/dL
10. Coagulopathy manifested by platelet count <100,000 or International Normalized ratio (INR) >1.7 (INR is only required in patients who have taken warfarin within 2 weeks of enrollment)
11. Patients in cardiogenic shock
12. Acute myocardial infarction (MI) within the past one (1) month, and/or signs of active myocardial ischemia at the time of enrollment including elevated Troponin-I or T (with concomitant elevation of CK), ischemic ECG changes or chest pain
13. History of a stroke or transient ischemic attack (TIA) within 3 months
14. NYHA class III or IV heart failure
15. Active peptic ulcer or upper gastrointestinal (GI) bleeding within 6 months
16. Patients with a life expectancy of less than 1 year
17. Target vessel < 2.4 mm in diameter
18. Target lesion > 32 mm in length
19. Chronic Total Occlusion (CTO)
20. Previous stent procedure within 5 mm of target lesion
21. Angiographic evidence of a target lesion severe dissection prior to Coronary Lithoplasty treatment
22. Unprotected Left Main diameter stenosis ≥ 50%
23. Visible thrombus (by angiography) at target lesion site
24. Target lesion is located in a native vessel distal to anastomosis with a saphenous vein graft or LIMA/RIMA bypass
25. Patient has active systemic infection
26. Patient has connective tissue disease (e.g., Marfan's syndrome)
27. Patient has a hypercoagulable disorder
28. Uncontrolled insulin dependent diabetes
29. Patient has allergy to imaging contrast media for which they cannot be pre-medicated
30. Evidence of aneurysm in target vessel
31. Patient is pregnant or nursing

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom

Administrative Information

• NCT Number: NCT03328949
• Other Study ID Numbers: CP61774
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Shockwave Medical, Inc.
• Study Sponsor: Shockwave Medical, Inc.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jean Fajadet, MD; Clinic Pasteur
• Principal Investigator: Carlo DiMario, MD; University of Florence

• PRS Account: Shockwave Medical, Inc.
• Verification Date: June 2019