Safety and Efficacy of Cardiac Shockwave Therapy in Patients Undergoing Coronary Artery Bypass Grafting

Study Overview
=================
Brief Summary
-----------------
This randomised, controlled clinical trial aims to evaluate the safety and efficacy of Cardiac Shockwave Therapy (CAST-HF) in patients with ischaemic heart failure requiring surgical revascularization. The main questions to answer are: Does cardiac shockwave therapy, in addition to CABG surgery, improve left ventricular ejection fraction? Is cardiac shockwave therapy in addition to CAGB surgery safe? Participants will be randomised into intervention (cardiac shockwave therapy) and control (sham treatment with an inactive applicator) groups.

Detailed Description
-----------------
This study investigates the safety and performance characteristics of the Direct Epicardial Shockwave Therapy System (DESWT) as applied with the Cardiac Shockwave Probe (CSP).

Official Title
-----------------
Safety and Efficacy of Cardiac Shockwave Therapy in Patients Undergoing Coronary Artery Bypass Grafting

Conditions
-----------------
Heart Failure Patients, Cardiac Ischemia

Intervention / Treatment
-----------------
* Device: Shockwave Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Male or female patients between 21 and 90 years of age undergoing primary coronary artery bypass grafting Presentation with reduced left ventricular function, defined as LVEF ≤ 40% measured by cardiac MRI Presentation with regional left ventricular wall motion abnormalities Written informed consent from the patient for participation in the study Exclusion criteria Significant concomitant aortic valve disease requiring surgical treatment (other than significant aortic valve disease not detected in preoperative cardiac ultrasound but detected during surgery) Serious radiographic contrast allergy Patient in cardiogenic shock or presenting with acute myocardial infarction (STEMI or NSTEMI) Patient with a contraindication for cardiac MRI History of significant ventricular arrhythmia, other than MI-associated arrhythmia Comorbidity reducing life expectancy to less than one year Presence of a ventricular thrombus Presence of a cardiac tumour Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study investigates the safety and performance characteristics of the Direct Epicardial Shockwave Therapy System (DESWT) as applied with the Cardiac Shockwave Probe (CSP) vs. Sham treatment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Arm<br>In the intervention arm, 300 shockwave impulses per coronary supply territory, at an energy flux density of 0.38mJ/mm2 and a frequency 3Hz, are applied in direct contact with the ischaemic myocardium of the left ventricle. The intervention is performed during CABG surgery after bypasses are fully established while still on cardiopulmonary bypass. | Device: Shockwave Therapy<br>* The cardiac shockwave system consists of a table-top device (Nonvasiv Medical GmbH, Konstanz, Germany) and a sterile single-use applicator releasing electrohydraulic shockwaves (Heart Regeneration Technologies GmbH, Innsbruck, Austria). Prior to use, the applicator is inserted into a sterile cover containing ultrasound gel. In order to ensure acoustic coupling between the applicator and the myocardium, continuous saline rinsing is applied throughout the procedure.<br>|
| No Intervention: Sham Control Arm<br>In the sham control arm, the same manipulations are performed with an inactive shockwave applicator in direct contact with the ischaemic myocardium of the left ventricle as in the intervention arm. The sham treatment is performed during CABG surgery after bypasses are fully established while still on cardiopulmonary bypass. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy endpoint is the improvement in LVEF measured by cardiac MRI from baseline to 360 days. | The primary efficacy objective is to assess the efficacy of cardiac shock wave therapy in patients undergoing primary coronary artery bypass grafting and suffering from reduced left ventricular function ≤ 40% | 360 days | 
| The primary safety endpoint is the occurrence of device-related complications (adverse device effects or serious adverse device effects) within 360 days. | The primary safety objective is to assess the safety profile of the cardiac shock wave therapy device. | 360 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary efficacy-related endpoints include patient-reported outcomes. | Change in: 6- Minute Walk Test Distance NYHA functional class Serum nt-proBNP levels Renal function (GFR) Seattle Angina Pectoris Questionnaire (SAQ) 36-item short-form survey (SF36) Minnesota Living with Heart Failure Questionnaire (MLHFQ) | 360 days | 
| Secondary safety-related endpoints include patient-reported outcomes. | Occurance of ventricular arrhythmia during hospital stay Occurrence of device-related peri-operative myocardial damage detected by rise of cardiac biomarkers (CK-MB, TropT) Occurrence of signs of device-related infection (CRP, leucocytosis) during hospital stay | 6 Days |