Shockwave Coronary Lithoplasty® Study (Disrupt CAD II)

• Sponsor: Shockwave Medical, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03328949
• Collaborator: (none)
• Enrollment: 120
• Locations: 15
• Arm: 1
• Actual Duration (Months): 11.2
• Patients Per Site: 8
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Device: IVL Coronary Lithotripsy System	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Intravascular Coronary Lithotripsy SystemIntravascular Coronary Lithotripsy System
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Multi-Center, Single Arm Post-Market Study (PMS) of the Shockwave Medical, Inc. Coronary Lithoplasty® System in Coronary Arteries
• Actual Study Start Date: May 18, 2018
• Actual Primary Completion Date: Mar 26, 2019
• Actual Study Completion Date: Apr 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IVL Coronary Lithotripsy System All enrolled patients will receive treatment from the IVL coronary lithotripsy system prior to coronary stent placement.	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).

Outcome Measures

Primary Outcome Measures

1. Number of Participants With In-hospital Major Adverse Cardiac Events (MACE) [Post-procedure through hospital discharge]

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

Secondary Outcome Measures

1. Number of Participants With Clinical Success [During procedure through hospital discharge]

   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.

2. Number of Participants With Angiographic Success [During procedure]

   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.

3. Number of Participants Which Experienced Cardiac Death [30 days post-procedure]

   Number of patients who experienced a cardiac death at 30 days post-procedure.

Eligibility Criteria

Criteria

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Onze-Lieve-Vrouwziekenhuis	Aalst		Belgium
2	Aarhus Universitetshospital	Aarhus		Denmark
3	Institut Hospitalier Jacques Cartier	Massy		France
4	Clinique Pasteur	Toulouse		France
5	Universitaets-Herzzentrum Freiburg- Bad Krozingen	Bad Krozingen		Germany
6	Universitaetsklinikum Bonn	Bonn		Germany
7	UKGM Universitaetsklinikum Giessen	Gießen		Germany
8	AOU Careggi SOD Interventistica	Firenze		Italy
9	San Raffaelle Hospital	Milan		Italy
10	Thorax Center, Erasmus MC	Rotterdam		Netherlands
11	Isala Zeikenhuis- Hartecentrum	Zwolle		Netherlands
12	Hospital Universitario San Carlos	Madrid		Spain
13	Uppsala University Hospital	Uppsala		Sweden
14	King's College Hospital	London		United Kingdom
15	Oxford University Hospitals, John Radcliffe Hospital	Oxford		United Kingdom

Sponsors and Collaborators

• Shockwave Medical, Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 18, 2019

More Information

Publications

None provided.

• Responsible Party: Shockwave Medical, Inc.
• ClinicalTrials.gov Identifier: NCT03328949
• Other Study ID Numbers: CP61774
• First Posted: Nov 1, 2017
• Last Update Posted: Nov 19, 2019
• Last Verified: Nov 1, 2019

• 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: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Coronary Artery Disease

Study Results

Participant Flow

Recruitment Details	Study recruitment and enrollment took place at 15 clinical sites in 9 European countries between May 2018 and March 2019. A total of 120 subjects with calcified, stenotic de novo coronary arteries were enrolled and treated with the Coronary Intravascular Lithotripsy (IVL) System.

Arm/Group Title	Coronary Intravascular Lithotripsy (IVL) System
Arm/Group Description	All enrolled patients will receive treatment from the coronary intravascular lithotripsy (IVL) system prior to coronary stent placement. Coronary Intravascular Lithotripsy (IVL) 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).
Period Title: Overall Study
STARTED	120
COMPLETED	120
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Coronary Intravascular Lithotripsy (IVL) System
Arm/Group Description	All enrolled patients will receive treatment from the coronary intravascular lithotripsy (IVL) system prior to coronary stent placement. Coronary Intravascular Lithotripsy (IVL) 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).
Overall Participants	120
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	31 25.8%
>=65 years	89 74.2%
Sex: Female, Male (Count of Participants)
Female	26 21.7%
Male	94 78.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 2.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	94 78.3%
More than one race	2 1.7%
Unknown or Not Reported	21 17.5%
Region of Enrollment (participants) [Number]
Netherlands	4 3.3%
Sweden	1 0.8%
Belgium	9 7.5%
Denmark	1 0.8%
Italy	25 20.8%
United Kingdom	19 15.8%
France	19 15.8%
Germany	29 24.2%
Spain	13 10.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With In-hospital Major Adverse Cardiac Events (MACE)
Description	The primary endpoint is the frequency of in-hospital major adverse cardiac events (MACE). MACE is defined as the following: Cardiac death Myocardial Infarction - 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
Time Frame	Post-procedure through hospital discharge

Outcome Measure Data

Analysis Population Description

No imputation of or adjustments for missing data were performed for the primary analysis. The population for all analysis was the Intent-To-Treat (ITT) analysis set. ITT was defined as those subjects who had insertion of the IVL catheter attempted, defined as the point of enrollment.

Arm/Group Title	Coronary Intravascular Lithotripsy (IVL) System
Arm/Group Description	All enrolled patients will receive treatment from the coronary intravascular lithotripsy (IVL) system prior to coronary stent placement. Coronary Intravascular Lithotripsy (IVL) 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).
Measure Participants	120
Count of Participants [Participants]	7 5.8%

2. Secondary Outcome

Title	Number of Participants With Clinical Success
Description	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.
Time Frame	During procedure through hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Coronary Intravascular Lithotripsy (IVL) System
Arm/Group Description	All enrolled patients will receive treatment from the coronary intravascular lithotripsy (IVL) system prior to coronary stent placement. Coronary Intravascular Lithotripsy (IVL) 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).
Measure Participants	120
Count of Participants [Participants]	120 100%

3. Secondary Outcome

Title	Number of Participants With Angiographic Success
Description	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.
Time Frame	During procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Coronary Intravascular Lithotripsy (IVL) System
Arm/Group Description	All enrolled patients will receive treatment from the coronary intravascular lithotripsy (IVL) system prior to coronary stent placement. Coronary Intravascular Lithotripsy (IVL) 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).
Measure Participants	120
Count of Participants [Participants]	120 100%

4. Secondary Outcome

Title	Number of Participants Which Experienced Cardiac Death
Description	Number of patients who experienced a cardiac death at 30 days post-procedure.
Time Frame	30 days post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Coronary Intravascular Lithotripsy (IVL) System
Arm/Group Description	All enrolled patients will receive treatment from the IVL coronary lithotripsy system prior to coronary stent placement. Coronary Intravascular Lithotripsy (IVL) 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).
Measure Participants	120
Count of Participants [Participants]	1 0.8%

Adverse Events

Time Frame	From time of enrollment through 30 days
Arm/Group Title	Coronary Intravascular Lithotripsy (IVL) System
Arm/Group Description	All enrolled patients will receive treatment from the IVL coronary lithotripsy system prior to coronary stent placement. Coronary Intravascular Lithotripsy (IVL) 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).
All Cause Mortality
	Coronary Intravascular Lithotripsy (IVL) System
	Affected / at Risk (%)	# Events
Total	1/120 (0.8%)
Serious Adverse Events
	Coronary Intravascular Lithotripsy (IVL) System
	Affected / at Risk (%)	# Events
Total	13/120 (10.8%)
Cardiac disorders
Acute myocardial infarction	1/120 (0.8%)	1
Angina pectoris	2/120 (1.7%)	2
Arrhythmia	2/120 (1.7%)	2
Atrial fibrillation	1/120 (0.8%)	1
Coronary artery dissection	3/120 (2.5%)	3
Mitral valve incompetence	1/120 (0.8%)	1
Paroxysmal atrioventricular block	1/120 (0.8%)	1
Tricuspid valve incompetence	1/120 (0.8%)	1
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/120 (0.8%)	1
General disorders
Death	1/120 (0.8%)	1
Infections and infestations
Pneumonia	1/120 (0.8%)	1
Investigations
Myocardial necrosis marker increased	1/120 (0.8%)	1
Psychiatric disorders
Delirium	1/120 (0.8%)	1
Vascular disorders
Aortic stenosis	1/120 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Coronary Intravascular Lithotripsy (IVL) System
	Affected / at Risk (%)	# Events
Total	29/120 (24.2%)
Cardiac disorders
Angina pectoris	2/120 (1.7%)	2
Coronary artery dissection	4/120 (3.3%)	4
Ear and labyrinth disorders
Vertigo	1/120 (0.8%)	1
Gastrointestinal disorders
Abdominal pain	1/120 (0.8%)	1
General disorders
Malaise	1/120 (0.8%)	1
Infections and infestations
Fungal skin infection	1/120 (0.8%)	1
Injury, poisoning and procedural complications
Fall	1/120 (0.8%)	1
Vascular access site haematoma	3/120 (2.5%)	3
Vascular access site pain	2/120 (1.7%)	2
Investigations
Myocardial necrosis marker increased	2/120 (1.7%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/120 (0.8%)	1
Musculoskeletal pain	1/120 (0.8%)	1
Pain in extremity	1/120 (0.8%)	1
Pain in jaw	1/120 (0.8%)	1
Nervous system disorders
Sciatica	1/120 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/120 (1.7%)	2
Skin and subcutaneous tissue disorders
Macule	1/120 (0.8%)	1
Vascular disorders
Haemodynamic instability	1/120 (0.8%)	1
Hypertension	1/120 (0.8%)	1
Orthostatic hypotension	1/120 (0.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After publication of the multi-center Study, or earlier with Sponsor's prior written consent, the Institution may publish the results of its subjects enrolled in the Study after first complying with this Section 9 of the contract. The Institution agrees to submit any proposed publications to Sponsor for review and comment at least forty-five (45) days in advance of submitting such proposed publications to a publisher or other third party.