Efficacy of Extracorporeal Shockwave Myocardial Revascularization Therapy in Patients With Stable Angina Pectoris

Efficacy of Extracorporeal Shockwave Myocardial Revascularization Therapy in Patients With Stable Angina Pectoris - A Randomized, Double Blind, Placebo Controlled, Multicenter Study

Low intensity shockwaves have been proven in animal and pilot clinical studies to induce local growth of new blood vessels. Small single-center clinical trials with shockwave therapy showed promising results in reducing angina symptoms, improving perfusion and contractility in patients with refractory angina and stress-induced ischemia on imaging test.

The hypothesis of this study is that shockwave therapy could improve angina symptoms and exercise tolerance in broader population of patients with stable angina regardless of imaging test results Study aims to demonstrate anti-anginal efficacy of Extracorporeal Shockwave Myocardial Revascularization Therapy (ESMR), on top of stable optimal medical treatment in patients with stable angina.

Study Overview

• Status: Completed
• Conditions: Stable Angina Pectoris
• Intervention / Treatment: Device: Active treatment group; Device: Placebo group

Detailed Description

Low intensity shockwaves (0.09 millijoule/mm2) are delivered to myocardial tissue. Shockwaves are created by a special generator and are focused using a shockwave applicator device. The treatment is guided by standard echocardiography equipment. The shockwaves are delivered in synchronization with Patient R-wave (ECG) to avoid arrhythmias. The treatment is painless.

At first, the patient undergoes modified Bruce treadmill test, to assess exercise induced ischemia.

Exercise induced ECG ischemia is defined as the new development of horizontal or down - sloping ST segment depression (≥1 mm at 60 ms after J point) versus baseline tracing.

Study treatment consists of 9 sessions, with 3 sessions per week 1, 5 and 9. 100 shocks are delivered per spot, 1200 shocks per session.

During 1st treatment week ESMR will be delivered 3 times (every other day) to basal segments (2 spots in each wall in apical 4-, 2-, 3- chamber positions).

During 2nd treatment week ESMR will be delivered 3 times (every other day) to middle segments (2 spots in each wall in apical 4-, 2-, 3- chamber positions).

During 3rd treatment week ESMR will be delivered 3 times (every other day) to apical segments (2 spots in each wall in apical 4-, 2-, 3- chamber positions).

The spots are localized by the ultra-sound device and the shockwaves are focused to this area. Several treatments are required for optimal results.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 3

Contacts and Locations

Study Locations

• Lithuania
  • Vilnius, Lithuania
    • Vilnius University Hospital, Santariskiu klinkos
• Russian Federation
  • Moscow, Russian Federation, 127473
    • Moscow state university of medicine&dentistry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients (females of childbearing potential must be using adequate contraceptive precautions such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or vasectomized partner).
• Patients aged ≥ 18 years.
• Patients with coronary artery disease confirmed by angiography, prior MI, prior revascularization (PCI, CABG) and with exercise angina not controlled by the optimal medical therapy.
• Patient should be on a stable dosage of medication used to treat angina for at least 4 weeks prior to enrollment.
• ST-segment depression ≥ 1mm during exercise ECG.
• Able and willing to sign informed consent and to comply with study procedures.
• Written informed consent prior to enrolment into the study.

Exclusion Criteria:

• Angina at rest.
• ECG abnormalities at rest (left bundle-branch block, resting ST-segment depression ≥ 1mm, digoxin therapy, WPW-syndrome).
• Planned coronary intervention or CABG within 6 months.
• Heart failure (class III or IV NYHA).
• Moderate-severe hypertension (SBP>160 mmHg and/or DBP>100 mmHg).
• Hypotension (SBP<100 mmHg).
• Acute coronary syndrome or coronary revascularization procedure within the prior 3 months before enrolment.
• Females who are pregnant or nursing.
• Any clinically relevant hematological or biochemical abnormality on routine screening, according to Investigator's judgment.
• Severe concurrent pathology, including terminal illness (cancer, AIDS, etc.).
• Renal impairment defined as Creatinine >150 mcmol/l.
• Mild, moderate or severe hepatic impairment or hepatic insufficiency defined as: SGOT or SGPT > 3 times greater than normal upper limit or total serum bilirubin > 1.5 times greater than normal upper limit
• Existing contraindications for exercise testing (e.g. acute myocarditis or pericarditis, DVT, severe aortic stenosis)
• Dementia, psychosis, alcoholism (>350 g ethanol/week) or chronic abuse of medicines, drugs or psychoactive substances.
• Conditions which in the Investigator's opinion may interfere with the study's execution or due to which the patient should not participate for safety reasons.
• Risk of low patient cooperation.
• Inability or unwillingness to issue the informed consent.
• Patient is simultaneously participating in another device or drug study, or has participated in any clinical trial involving an experimental device or drug, including other drugs or devices enhancing cardiac neovascularization, or any cardiac shock wave therapy machine of a competitor company within 3 months of entry into the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active treatment group; Patients in this group receive actual shockwave therapy. Study treatment consists of 9 sessions, with 3 sessions per week 1, 5 and 9. 100 shocks are delivered per spot, 1200 shocks per session. During 1st treatment week ESMR will be delivered 3 times (every other day) to basal segments (2 spots in each wall in apical 4-, 2-, 3- chamber positions). During 2nd treatment week ESMR will be delivered 3 times (every other day) to middle segments (2 spots in each wall in apical 4-, 2-, 3- chamber positions). During 3rd treatment week ESMR will be delivered 3 times (every other day) to apical segments (2 spots in each wall in apical 4-, 2-, 3- chamber positions).	Device: Active treatment group; Energy Density - 0.09 mJ/mm2 Device: Active Applicator; Other Names: Cardiospec; Extracorporeal Shockwave Myocardial Revascularization (ESMR); Extracorporeal Cardiac Shock wave therapy (CSWT)
Placebo Comparator: Placebo group; This group of patients undergoes the same procedure as the treatment group; however shockwaves are not delivered to the heart.	Device: Placebo group; Placebo Applicator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Exercise duration	To evaluate if ESMR able to improve total exercise duration in modified Bruce treadmill test. Patients will be assessed at baseline visit (screening) and 6 months after the first treatment.	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to 1 mm ST-segment depression in modified Bruce treadmill test	6 months
Time to angina in modified Bruce treadmill test	6 months
Number of angina attacks per week	6 months
Number of sublingual nitroglycerin consumption per week	6 months
CCS angina functional class	6 months
Seattle angina questionnaire score	6 months

Collaborators and Investigators

• Sponsor: Evgeny Shkolnik, MD
• Collaborators: Vilnius University; Medispec
• Investigators: Principal Investigator: Jelena Celutkiene, MD, PhD, Vilnius University Hospital, Santariskiu klinikos; Principal Investigator: Evgeny Shkolnik, MD, PhD, Moscow state university of medicine&dentistry

Publications and helpful links

General Publications

• Celutkiene J, Burneikaite G, Shkolnik E, Jakutis G, Vajauskas D, Cerlinskaite K, Zuoziene G, Petrauskiene B, Puronaite R, Komiagiene R, Butkuviene I, Steponeniene R, Misiura J, Laucevicius A. The effect of cardiac shock wave therapy on myocardial function and perfusion in the randomized, triple-blind, sham-procedure controlled study. Cardiovasc Ultrasound. 2019 Jul 4;17(1):13. doi: 10.1186/s12947-019-0163-1.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: January 12, 2015
• First Submitted That Met QC Criteria: January 14, 2015
• First Posted (Estimate): January 15, 2015

Study Record Updates

• Last Update Posted (Actual): April 10, 2018
• Last Update Submitted That Met QC Criteria: April 7, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: stable angina; exercise tolerance; Cardiac Shock wave therapy
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Angina, Stable
• Other Study ID Numbers: ESMR-RCT-UP