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

NCT ID: NCT02339454

Last Updated: 2018-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2017-12-31

Brief Summary

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.

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.

Conditions

Stable Angina Pectoris

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Active treatment group

Intervention Type: DEVICE

Energy Density - 0.09 mJ/mm2 Device: Active Applicator

Placebo group

This group of patients undergoes the same procedure as the treatment group; however shockwaves are not delivered to the heart.

Group Type: PLACEBO_COMPARATOR

Placebo group

Intervention Type: DEVICE

Placebo Applicator

Interventions

Active treatment group

Energy Density - 0.09 mJ/mm2 Device: Active Applicator

Intervention Type: DEVICE

Placebo group

Placebo Applicator

Intervention Type: DEVICE

Other Intervention Names

Cardiospec; Extracorporeal Shockwave Myocardial Revascularization (ESMR); Extracorporeal Cardiac Shock wave therapy (CSWT)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vilnius University

OTHER

Sponsor Role: collaborator

Medispec

INDUSTRY

Sponsor Role: collaborator

Evgeny Shkolnik, MD

OTHER

Sponsor Role: lead

Responsible Party

Evgeny Shkolnik, MD

Professor, department of functional methods in internal medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jelena Celutkiene, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vilnius University Hospital, Santariskiu klinikos

Evgeny Shkolnik, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Moscow State University of Medicine&Dentistry

Locations

Vilnius University Hospital, Santariskiu klinkos

Vilnius, , Lithuania

Moscow state university of medicine&dentistry

Moscow, , Russia

Countries

Lithuania; Russia

References

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.

Reference Type: DERIVED

PMID: 31272465 (View on PubMed)

Other Identifiers

ESMR-RCT-UP

Identifier Type: -

Identifier Source: org_study_id