Shockwave C2+ 2Hz Coronary IVL Catheter in Calcified Coronary Arteries (Disrupt CAD DUO)

• Sponsor: Shockwave Medical, Inc. (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05966662
• Collaborator: (none)
• Enrollment: 145
• Arm: 1
• Anticipated Duration (Months): 23

Study Details

Study Description

Brief Summary

This investigational device exemption (IDE) study is to assess the safety and effectiveness of the Shockwave Coronary Intravascular Lithotripsy (IVL) System with the Shockwave C2+ 2Hz Coronary IVL Catheter to treat de novo, calcified, stenotic, coronary lesions prior to stenting.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease; Myocardial Infarction	Device: IVL with Shockwave C2+ 2Hz Coronary IVL Catheter	N/A

Detailed Description

The Shockwave Coronary Intravascular Lithotripsy (IVL) System with the Shockwave C2+ 2Hz Coronary IVL Catheter is indicated for lithotripsy-enabled, low-pressure balloon dilatation of severely calcified, stenotic de novo coronary arteries prior to stenting.

Up to 145 subjects (138 evaluable) subjects with de novo, calcified coronary artery lesions presenting with stable, unstable, or silent ischemia that are suitable for percutaneous coronary intervention (PCI) will be enrolled at up to 20 US sites.

Enrollment duration will be approximately 10-12 months and study duration will be approximately 2 years.

Each subject will be followed through discharge, 30 days, 6, and 12 months.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 145 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Shockwave C2+ 2Hz Coronary IVL Catheter with Shockwave Intravascular Lithotripsy (IVL) SystemShockwave C2+ 2Hz Coronary IVL Catheter with Shockwave Intravascular Lithotripsy (IVL) System
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective, Multicenter, Single-Arm IDE Study of the Shockwave Coronary Intravascular Lithotripsy (IVL) System With the Shockwave C2+ 2Hz Coronary IVL Catheter in Calcified Coronary Arteries (Disrupt CAD Duo Study)
• Anticipated Study Start Date: Oct 1, 2023
• Anticipated Primary Completion Date: Oct 1, 2024
• Anticipated Study Completion Date: Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single-Arm Subjects with de novo, calcified coronary artery lesions presenting with stable, unstable, or silent ischemia that are suitable for percutaneous coronary intervention (PCI).	Device: IVL with Shockwave C2+ 2Hz Coronary IVL Catheter; Lithotripsy-enabled, low-pressure balloon dilatation of severely calcified, stenotic de novo coronary arteries prior to stenting.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced Freedom From Major Adverse Cardiac Events (MACE) Within 30 Days Post-procedure [30 days of the index procedure]

   The primary safety endpoint was freedom from MACE within 30 days of the index procedure. MACE is defined as a composite occurrence of: 1) Cardiac death; or 2) Myocardial Infarction (MI) (using the SCAI definition for peri-procedural MI; using the 4th Universal Definition for spontaneous MI beyond discharge); or 3) Target Vessel Revascularization (TVR) defined as revascularization at the target vessel (inclusive of the target lesion) after the completion of the index procedure

2. Number of Participants With Procedural Success (Residual Stenosis <30%) [12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure]

   The primary effectiveness endpoint will be evaluated as the following: Procedural Success defined as stent delivery with a residual stenosis ≤30% (core laboratory assessed) and without in-hospital MACE.

Secondary Outcome Measures

1. Number of Participants with Device Crossing Success [at the end of procedure]

   Device Crossing Success is defined as the ability to deliver the IVL catheter across the target lesion, and delivery of lithotripsy without serious angiographic complications immediately after IVL.

2. Number of Participants With Angiographic Success (Residual Stenosis <50%) [at the end of procedure]

   Angiographic Success defined as stent delivery with <50% residual stenosis and without serious angiographic complications.

3. Number of Participants With Procedural Success (Residual Stenosis <=30%) [12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure]]

   Procedural Success defined as stent delivery with a residual stenosis <50% (core laboratory assessed) and without in-hospital MACE.

4. Number of Participants With Angiographic Success (Residual Stenosis <=30%) [at end of procedure]

   Angiographic Success defined as stent delivery with ≤30% residual stenosis and without serious angiographic complications.

5. Number of Participants With Serious Angiographic Complications [at end of procedure]

   Serious angiographic complications defined as severe dissection (Type D to F), perforation, abrupt closure, and persistent slow flow or persistent no reflow.

6. MACE Rate at 6 Months [within 6 months of index procedure]

   MACE at 6 months - a composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR) - is presented as a Kaplan-Meier estimated event rate.

7. MACE Rate at 12 Months [within 12 months of index procedure]

   MACE at 12 months - a composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR) - is presented as a Kaplan-Meier estimated event rate.

8. Target Lesion Failure (TLF) Rate at 30 Days [within 30 days of index procedure]

   Target lesion failure (TLF) is defined as cardiac death, target vessel myocardial infarction (Q wave and non-Q wave), or ischemia-driven target lesion revascularization (ID-TLR) by percutaneous or surgical methods. 30 day rates are presented as proportions.

9. Target Lesion Failure (TLF) Rate at 6 Months [within 6 months of index procedure]

   TLF is defined as cardiac death, target vessel myocardial infarction (Q wave and non-Q wave), or ischemia-driven target lesion revascularization (ID-TLR) by percutaneous or surgical methods. For 6 months, rates are presented as Kaplan-Meier estimated event rates.

10. Target Lesion Failure (TLF) Rate at 12 Months [within 12 months of index procedure]

    TLF is defined as cardiac death, target vessel myocardial infarction (Q wave and non-Q wave), or ischemia-driven target lesion revascularization (ID-TLR) by percutaneous or surgical methods. For 12 months, rates are presented as Kaplan-Meier estimated event rates

11. All-Cause Death Rate at 30 Days [within 30 days of index procedure]

    30-day rates are presented as proportions.

12. All-Cause Death Rate at 6 Months [within 6 months of index procedure]

    All-cause death at 6 months is presented as a Kaplan-Meier estimated event rate.

13. All-Cause Death Rate at 12 Months [within 12 months of index procedure]

    All-cause death at 12 months is presented as a Kaplan-Meier estimated event rate.

14. Cardiac Death Rate at 30 Days [within 30 days of index procedure]

    30-day rates are presented as proportions

15. Cardiac Death Rate at 6 Months [within 6 months of index procedure]

    Cardiac death at 6 months is presented as a Kaplan-Meier estimated event rate.

16. Cardiac Death Rate at 12 Months [within 12 months of index procedure]

    Cardiac death at 12 months is presented as a Kaplan-Meier estimated event rate.

17. MI Rate at 30 Days [within 30 days of index procedure]

    30-day rates are presented as proportions.

18. MI Rate at 6 Months [within 6 months of index procedure]

    MI is presented as a Kaplan-Meier estimated event rate at 6 months.

19. MI Rate at 12 Months [within 12 months of index procedure]

    MI is presented as a Kaplan-Meier estimated event rate at 12 months.

20. Target Vessel-Myocardial Infarction (TV-MI) Rate at 30 Days [within 30 days of index procedure]

    30-day rates are presented as proportions.

21. TV-MI Rate at 6 Months [within 6 months of index procedure]

    TV-MI is presented as a Kaplan-Meier estimated event rate at 6 months.

22. TV-MI Rate at 12 Months [within 12 months of index procedure]

    TV-MI is presented as a Kaplan-Meier estimated event rate at 12 months.

23. Procedural MI Rate at 30 Days [within 30 days of index procedure]

    Periprocedural MI defined as fourth universal definition and CK-MB > 3x upper limit of lab normal (ULN). 30-day rates are presented as proportions.

24. Procedural MI Rate at 6 Months [within 6 months of index procedure]

    Periprocedural MI defined as fourth universal definition and CK-MB > 3x upper limit of lab normal (ULN). For 6 months, rates are presented as Kaplan-Meier estimated event rates.

25. Procedural MI Rate at 12 Months [within 12 months of index procedure]

    Periprocedural MI defined as fourth universal definition and CK-MB > 3x upper limit of lab normal (ULN). For 12 months, rates are presented as Kaplan-Meier estimated event rates.

26. Non-Procedural MI Rate at 30 Days [within 30 days of index procedure]

    Non-Procedural MI defined as spontaneous MI beyond discharge (4th Universal Definition). 30-day rates are presented as proportions.

27. Non-Procedural MI Rate at 6 Months [within 6 months of index procedure]

    Non-Procedural MI defined as spontaneous MI beyond discharge (4th Universal Definition). For 6 months, rates are presented as Kaplan-Meier estimated event rates.

28. Non-Procedural MI Rate at 12 Months [within 12 months of index procedure]

    Non-Procedural MI defined as spontaneous MI beyond discharge (4th Universal Definition). For 12 months, rates are presented as Kaplan-Meier estimated event rates.

29. Ischemia-Driven Target Vessel Revascularization (ID-TVR) Rate at 30 Days [within 30 days of index procedure]

    30-day rates are presented as proportions.

30. ID-TVR Rate at 6 Months [within 6 months of index procedure]

    For 6 months, rates are presented as Kaplan-Meier estimated event rates.

31. ID-TVR Rate at 12 Month [within 12 months of index procedure]

    For 12 months, rates are presented as Kaplan-Meier estimated event rates.

32. Ischemia-Driven Target Lesion Revascularization (ID-TLR) Rate at 30 Days [within 30 days of index procedure]

    30-day rates are presented as proportions.

33. ID-TLR Rate at 6 Months [within 6 months of index procedure]

    For 6 months, rates are presented as Kaplan-Meier estimated event rates.

34. ID-TLR Rate at 12 Months [within 12 months of index procedure]

    For 12 months, rates are presented as Kaplan-Meier estimated event rates.

35. Non-ID-TVR Rate at 30 Days [within 30 days of index procedure]

    30-day rates are presented as proportions

36. Non-ID-TVR Rate at 6 Months [within 6 months of index procedure]

    For 6 months, rates are presented as Kaplan-Meier estimated event rates.

37. Non-ID-TVR Rate at 12 Months [within 12 months of index procedure]

    For 12 months, rates are presented as Kaplan-Meier estimated event rates.

38. Non-ID-TLR Rate at 30 Days [within 30 days of index procedure]

    30-day rates are presented as proportions

39. Non-ID-TLR Rate at 6 Months [within 6 months of index procedure]

    For 6 months, rates are presented as Kaplan-Meier estimated event rates.

40. Non-ID-TLR Rate at 12 Months [within 12 months of index procedure]

    For 12 months, rates are presented as Kaplan-Meier estimated event rates.

41. Any Revascularizations Rate at 30 Days [within 30 days of index procedure]

    Any revascularizations (ID and non-ID) at 30 days. 30-day rates are presented as proportions.

42. Any Revascularizations Rate at 6 months [within 6 months of index procedure]

    Any revascularizations (ID and non-ID) at 6 months, presented as a Kaplan-Meier estimated event rate.

43. Any Revascularizations Rate at 12 months [within 12 months of index procedure]

    Any revascularizations (ID and non-ID) at 12 months, presented as a Kaplan-Meier estimated event rate

44. Stent Thrombosis Rate at 30 Days [within 30 days of index procedure]

    Any stent thrombosis (definite, probable, definite or probable) according to Academic Research Consortium (ARC) criteria, as referenced from Cutlip, D.E. et al. Clinical End Points in Coronary Stent Trials. Circ. 2007.115.2344-51. 30-day rates are presented as proportions.

45. Stent Thrombosis Rate at 6 Months [within 6 months of index procedure]

    Any stent thrombosis (definite, probable, definite or probable) according to Academic Research Consortium (ARC) criteria, as referenced from Cutlip, D.E. et al. Clinical End Points in Coronary Stent Trials. Circ. 2007.115.2344-51. For 6 months, rates are presented as Kaplan-Meier estimated event rates.

46. Stent Thrombosis Rate at 12 Months [within 12 months of index procedure]

    Any stent thrombosis (definite, probable, definite or probable) according to Academic Research Consortium (ARC) criteria, as referenced from Cutlip, D.E. et al. Clinical End Points in Coronary Stent Trials. Circ. 2007.115.2344-51. For 12 months, rates are presented as Kaplan-Meier estimated event rates.

47. Rate of MI Using the 4th Universal Definition at 30 Days [within 30 days of index procedure]

    30-day rates are presented as proportions.

48. Rate of MI Using the 4th Universal Definition at 6 months [within 6 months of index procedure]

    For 6 months, rates are presented as Kaplan-Meier estimated event rates.

49. Rate of MI Using the 4th Universal Definition at 12 months [within 12 months of index procedure]

    For 12 months, rates are presented as Kaplan-Meier estimated event rates.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:Subjects are required to meet all of the following inclusion criteria in order to be enrolled in the clinical study.

General 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 subjects with unstable ischemic heart disease, biomarkers (CK-MB and troponin) must be less than or equal to the upper limit of the laboratory normal within 12 hours prior to the procedure (note: both must be normal)

4. For subjects 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

5. If drawn prior to the procedure, biomarkers (CK-MB and troponin) must be less than or equal to the upper limit of the laboratory normal within 12 hours of the procedure (note: both must be normal)

6. If 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

7. 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 criterion; may be assessed at time of index procedure)

8. Subject or legally authorized representative, signs a written Informed Consent form to participate in the study, prior to any study-mandated procedures

9. Non-target lesions requiring PCI may be treated either

10. 30 days prior to the study procedure if the procedure was unsuccessful or complicated; or

11. 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

12. 30 days after the study procedure

Angiographic Inclusion Criteria

1. The target lesion must be a de novo coronary lesion that has not been previously treated with any interventional procedure

2. Single de novo target lesion stenosis of protected LMCA, or LAD, RCA or LCX (or of their branches) with

3. Stenosis of ≥70% and <100%, or

4. 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

5. The target vessel reference diameter must be ≥2.5 mm and ≤4.0 mm

6. The lesion length must not exceed 40 mm

7. The target vessel must have TIMI flow 3 at baseline (visually assessed; may be assessed after pre- dilatation)

8. 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

9. Ability to pass a 0.014" guide wire across the lesion

Exclusion Criteria: Subjects who meet any of the following exclusion criteria may not be enrolled in the study:

General Exclusion Criteria

1. Any comorbidity or condition which may reduce compliance with this protocol, including follow-up visits

2. Subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached the primary endpoint

3. Subject is pregnant or nursing (a negative pregnancy test is required for women of child-bearing potential within 7 days prior to enrollment)

4. Unable to tolerate antiplatelet/anticoagulation therapy per society guidelines

5. Subject has an allergy to imaging contrast media which cannot be adequately pre-medicated

6. 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 greater than 1 times the local laboratory's upper limit of normal

7. New York Heart Association (NYHA) class III or IV heart failure

8. Subject has acute or chronic renal disease with eGFR <30 ml/min/1.73m2 (using CKD-EPI formula)

9. History of a stroke or transient ischemic attack (TIA) within 60 days, or any prior intracranial hemorrhage or permanent neurologic deficit

10. Active peptic ulcer or upper gastrointestinal (GI) bleeding within 3 months

11. Untreated pre-procedural hemoglobin <10 g/dL or intention to refuse blood transfusions if one should become necessary

12. 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)

13. Subject has a hypercoagulable disorder such as polycythemia vera, platelet count

750,000 or other related blood disorders

1. Subject has an active systemic infection on the day of the index procedure with either fever, leukocytosis or requiring intravenous antibiotics

2. Subjects with clinical evidence of cardiogenic shock

3. Uncontrolled severe hypertension (systolic BP >180 mm Hg or diastolic BP >110 mm Hg)

4. Subjects with a life expectancy of less than 1 year

5. Non-coronary interventional or surgical structural heart procedures (e.g., TAVR, MitraClip, LAA or PFO occlusion, etc.) within 30 days prior to the index procedure

6. Planned non-coronary interventional or surgical structural heart procedures (e.g., TAVR, MitraClip, LAA or PFO occlusion, etc.) within 30 days after the index procedure

7. Subject refusing or not a candidate for emergency coronary artery bypass grafting (CABG) surgery

8. Planned use of atherectomy, scoring or cutting balloon, or any investigational device other than lithotripsy

Angiographic Exclusion Criteria

1. Unprotected left main diameter stenosis >30%

2. Definite or possible thrombus (by angiography or intravascular imaging) in the target vessel

3. Evidence of aneurysm in target vessel within 10 mm of the target lesion

4. Target lesion is located in a native vessel that can only be reached by going through a saphenous vein or arterial bypass graft

5. Previous stent within 5 mm of the target lesion regardless of the timing of its implantation

6. Angiographic evidence of a dissection or perforation in the target vessel at baseline or after guidewire passage

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Shockwave Medical, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shockwave Medical, Inc.
• ClinicalTrials.gov Identifier: NCT05966662
• Other Study ID Numbers: CP 68277
• First Posted: Aug 1, 2023
• Last Update Posted: Aug 1, 2023
• Last Verified: Jul 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Shockwave Medical, Inc.: Intravasular Lithotripsy; PCI
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Infarction; Infarction

Study Results

No Results Posted as of Aug 1, 2023