Coronary Artery Disease
Conditions
Keywords
Coronary Artery Disease, Calcified Coronary Lesions, Coronary Arterial Stenosis
Brief summary
Prospective, multi-center, single arm study designed to evaluate the safety and performance of the Shockwave Coronary Rx Lithoplasty® System to treat calcified lesions in the coronary arteries for the purpose of enhancing the placement of stents and reducing the ultimate residual stenosis. Patients will be followed through discharge and at 30 and 180 days.
Detailed description
Prospective, multi-center, single arm study designed to evaluate the safety and performance of the Shockwave Coronary Rx Lithoplasty® System to treat calcified lesions in the coronary arteries for the purpose of enhancing the placement of stents and reducing the ultimate residual stenosis. Patients will be enrolled and consented in the study based on history and in some instances an angiogram obtained prior to the study. The study is designed to demonstrate that the Shockwave device can safely and effectively deliver localized shockwave energy for balloon dilatation of calcified, stenotic, coronary arteries. Subjects will be prepared for PCI per the institution's standard protocol. Medications will be administered per the treatment protocol. Femoral access will be obtained using a 6F access sheath, and guiding catheter placed at the ostia of the right or left coronary artery. Baseline angiography of the culprit lesion will be performed prior to placement of a 0.014 guide wire. Baseline and either IVUS or OCT will be performed to determine the Maximum Lumen Area (MLA), percent stenosis, and volumetric lesion assessment. Baseline angiography will be performed to determine lesion length, % stenosis and reference vessel diameter. The investigational device will be prepped per the IFU and positioned at the target lesion. The distal end of the balloon catheter will be connected to the patient cable. The balloon catheter will be inflated to 4 atm and the investigator will deliver 10 pulses for 20 seconds. The balloon will then be inflated to reference vessel diameter and then deflated to reestablish flow and complete one treatment cycle. The treatment cycle will then be repeated. Angiography and either IVUS or OCT will be repeated for the treated lesion.. A coronary stent will be deployed at the site of treatment. Angiography and either IVUS or OCT will be performed following stent placement. Patients will be followed through discharge and at 30 and 180 days. A subset of up to five (5) subjects will receive an angiographic assessment at the 180 day follow up visit, per the Sponsor's discretion.
Interventions
DEVICEShockwave Coronary Rx Lithoplasty® System
The Shockwave Coronary Rx Lithoplasty® System is a proprietary balloon catheter system designed to deliver localized, lithotripsy-enhanced, balloon dilatation of calcified, stenotic, de novo coronary arteries. Energizing the lithotripsy electrodes will generate pulsatile mechanical energy within the target treatment site and will disrupt calcium within the lesion and allow subsequent dilatation of a coronary artery stenosis using low balloon pressure. The system consists of a rapid exchange balloon catheter with integrated, internal lithotripsy electrodes and a Shockwave generator.
Sponsors
Shockwave Medical, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 12 hours prior to the procedure 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 lesions 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 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 elevated Troponin-I or T (with concomitant elevation of CPK) at the time of enrollment. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Frequency of Major Adverse Cardiac Events (MACE) Within 30 Days of the Procedure. | 30 days | MACE defined as: * 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 the target lesion) after the completion of the index procedure |
| Performance | Post-procedure (within 24 hours following procedure and prior to discharge) | The ability of the Shockwave System to produce acceptable residual stenosis (\<50%) after stenting with no evidence of in-hospital MACE. Clinical success measured by each patient that achieves both these requirements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative Assessment of the Residual Stenosis in Treated Lesions | Post-procedure (within 24 hours following procedure and prior to discharge) | Angiographic success defined as success in facilitating stent deliver 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 |
| 180 Day MACE | 180 days post-procedure | MACE defined as: * 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 the target lesion) after the completion of the index procedure |
Countries
Australia, France, Netherlands, Sweden, United Kingdom
Participant flow
Recruitment details
Study recruitment and enrollment took place at seven clinical sites in Australia and Europe between December 2015 and September 2016. A total of 60 subjects with calcified, stenotic de novo coronary arteries were enrolled and treated with the investigational device.
Participants by arm
| Arm | Count |
|---|---|
| Shockwave Coronary Rx Lithoplasty System Shockwave Coronary Rx Lithoplasty® System is a lithotripsy-enhanced, low-pressure balloon dilation of calcified, stenotic de novo coronary arteries prior to stent placement
Shockwave Coronary Rx Lithoplasty® System: The Shockwave Coronary Rx Lithoplasty® System is a proprietary balloon catheter system designed to deliver localized, lithotripsy-enhanced, balloon dilatation of calcified, stenotic, de novo coronary arteries. Energizing the lithotripsy electrodes will generate pulsatile mechanical energy within the target treatment site and will disrupt calcium within the lesion and allow subsequent dilatation of a coronary artery stenosis using low balloon pressure. The system consists of a rapid exchange balloon catheter with integrated, internal lithotripsy electrodes and a Shockwave generator. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | Shockwave Coronary Rx Lithoplasty System |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 47 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Region of Enrollment Australia | 16 Participants |
| Region of Enrollment France | 10 Participants |
| Region of Enrollment Netherlands | 4 Participants |
| Region of Enrollment Sweden | 1 Participants |
| Region of Enrollment United Kingdom | 29 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 60 |
| other Total, other adverse events | 37 / 60 |
| serious Total, serious adverse events | 10 / 60 |
Outcome results
Primary
Performance
The ability of the Shockwave System to produce acceptable residual stenosis (\<50%) after stenting with no evidence of in-hospital MACE. Clinical success measured by each patient that achieves both these requirements.
Time frame: Post-procedure (within 24 hours following procedure and prior to discharge)
Population: No imputation of or adjustments for missing data were performed for the primary analyses. The population for all analysis was the Intent-To-Treat (ITT) analysis set. ITT was defined as the subjects who had insertion of the Lithoplasty catheter attempted, defined as the point of enrollment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Coronary Rx Lithoplasty System | Performance | 57 Participants |
Primary
Safety - Frequency of Major Adverse Cardiac Events (MACE) Within 30 Days of the Procedure.
MACE defined as: * 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 the target lesion) after the completion of the index procedure
Time frame: 30 days
Population: No imputation of or adjustments for missing data were performed for the primary analyses. The population for all analysis was the Intent-To-Treat (ITT) analysis set. ITT was defined as those subjects who had insertion of the Lithoplasty catheter attempted, defined as the point of enrollment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Shockwave Coronary Rx Lithoplasty System | Safety - Frequency of Major Adverse Cardiac Events (MACE) Within 30 Days of the Procedure. | 57 events |
Secondary
180 Day MACE
MACE defined as: * 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 the target lesion) after the completion of the index procedure
Time frame: 180 days post-procedure
Population: No imputation of or adjustments for missing data were performed for the primary analyses. The population for all analysis was the Intent-To-Treat (ITT) analysis set. ITT was defined as those subjects who had insertion of the Lithoplasty catheter attempted, defined as the point of enrollment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Shockwave Coronary Rx Lithoplasty System | 180 Day MACE | 58 events |
Secondary
Quantitative Assessment of the Residual Stenosis in Treated Lesions
Angiographic success defined as success in facilitating stent deliver 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: Post-procedure (within 24 hours following procedure and prior to discharge)
Population: No imputation of or adjustments for missing data were performed for the primary analyses. The population for all analysis was the Intent-To-Treat (ITT) analysis set. ITT was defined as those subjects who had insertion of the Lithoplasty catheter attempted, defined as the point of enrollment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Coronary Rx Lithoplasty System | Quantitative Assessment of the Residual Stenosis in Treated Lesions | 58 Participants |