SONOlysis in Risk REduction of Symptomatic and Silent Brain infarCtions dUring Cardiac surgEry

NCT ID: NCT01591018

Last Updated: 2020-10-30

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2015-07-31

Brief Summary

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The aim of the project is to demonstrate a fibrinolytic effect of sonothrombolysis (continual transcranial Doppler monitoring) using 2 MHz diagnostic probe on the reduction of risk of brain infarctions due to the activation of endogenous fibrinolytic system during cardiac surgery (CS). 120 patients indicated for CS (CABG or valve replacement) will be enrolled into the study in order to demonstrate a twenty-percent risk reduction of number and volume of brain infarctions detected using MRI examination 24 hours after CEA or CS in 5% level of significance. Patients will be randomized - subgroup 1 will undergo a 40-240minute non-diagnostic TCD monitoring during CS, subgroup 2 will undergo interventions without TCD monitoring.

The aim of the project is a concordance with the aim No 1 of the Resort Program of a Research and Development: "Improvement of quality of life of patients using the modern therapeutic methods but with relative small positive effect of quality of life". The aim of the project is in concordance with a priority of announced public grant competition: "Development of the new therapeutic methods of cardiovascular disorders, especially coronary heart disease and stroke". Confirmation of our hypothesis that sonothrombolysis is able to activate endogenous fibrinolytic system during CS with consecutive reduction of the number and volume of brain infarcts, can lead to the increase of the safety of CS in patients. We can presume that up to 50% of patients indicated for CS can be treated using these methods in the future.

Detailed Description

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AIM OF THE PROJECT The aim of the project is to demonstrate an effect of continual TCD monitoring using 2 MHz diagnostic probe with maximal diagnostic energy on the reduction of risk of brain microinfarctions due to the activation of endogenous fibrinolytic system and mechanical effect on emboli during CS.

The aim of the project is a concordance with the aim No 1 of the Resort program of a research and development in the years 2010-2015: "Improvement of quality of life of patients using the modern therapeutic methods but with relative small positive effect of quality of life". The aim of the project is in concordance with a priority of announced public grant competition: "Development of the new therapeutic methods of cardiovascular disorders, especially coronary heart disease and stroke".

HYPOTHESIS Sonothrombolysis lead to activation of fibrinolytic system in both healthy volunteers and acute stroke patients. In acute stroke patients, mechanical effect of sonothrombolysis is the second effect leading to acceleration of occluded artery recanalization. We hypothesize that combination of mechanical effect and activation of fibrinolytic system durin sonothrombolysis (TCD monitoring) during CS will lead to recanalization of small arterial occlusions caused by microembolization during intervention. The result will be reduction of volume and the number of brain infarctions in the territory of the monitored MCA.

120 patients indicated for CS will be enrolled into the study in order to demonstrate a twenty-percent risk reduction of number and volume of brain infarctions in the territory of athe monitored MCA detected using MRI examination 24 hours after CS in 5% level of statistical significance. Patients will be randomized into 2 subgroups. Subgroup 1 will undergo non-diagnostic TCD monitoring during CS. Subgroup 2 will undergo CS without TCD monitoring.

PATIENTS AND METHODS Patients: 120 patients indicated for CS (isolated coronary artery bypass surgery or isolated heart valve surgery) will be enrolled into the study during a 3-year period. All 120 patients will be randomized for standard CS and TCD monitored CS.

Clinical examinations: Physical and neurological examinations including evaluating of neurological impairment of neurological deficit in NIHSS scale, modified Rankin scale and cognitive testing (Mini Mental State Examination, Clock drawing test) will be performed before and 24 - 72 hours after CS.

Randomization: Randomization using computer generated random allocation will be used, separately for coronary artery bypass surgery and valve surgery patients.

Sonothrombolysis: In patients randomized into sonothrombolysis subgroup, MCA segment in depth 55 mm will be monitored for 40 - 240 minutes using a diagnostic 2 MHz probe with maximal diagnostic energy. Non-diagnostic TCD monitoring will be performed without detection of microembolic signals or detection of changes in blood flow. The second (control) subgroup will undergo a standard CS without sonothrombolysis.

MRI protocol will consists of 4 sequences: 1. Localizer; 2. T2TSE; 3. FLAIR; 4. DWI. Sequences 1-3 will be applied in the same level, they will have the same slice thickness and the same cut number. The slice thickness comprises its own cut thickness (5 mm) + distant factor (30%). Standard number of slices is 19. Standard slice level is considered to be a modified level of skull base due to the minimalization of distant artifacts EPI sequence. T2TSE: TR=4000/TE=99/ETL=9, FOV 230, FOV ph. 75%, matrix 256x256. FLAIR: 8050/112/ETL=21/2 conc., FOV 230, FOV ph. 76,6%, matrix 256x151. EPI-DWI: 4200/139/EPI f.=96/6 av., FOV 230, FOV ph. 100%, phase enc. direction A-P, matrix 128x96 with interpolation, phase partial Fourier 6/8, Bw 1346 Hz/Px, echo spacing 0.83 ms, TA. Sequence called "trace" with three types of MR pictures in every slice: (a) T2\*EPI b=0; (b) DWI b=500; (c) DWI b=1000. The fourth type of images automatically created an ADC map (in-line postprocessing). DWI show a middle (average) diffusivity of every point of examined brain tissue when b value is 500 and 1000. This sequence is applied in order to assess hemorrhage (T2\*EPI) and monitor sites of reduced diffusion (DWI, b=500 and 1000). New infarctions will be evaluated only in the territory of treated ICA.

Adverse effects: All adverse effects during 1 month after UM will be registered, especially all causes for new admissions to the hospital, worsening of neurological symptoms (\>4 points in NIH stroke scale), brain edema, symptomatic and asymptomatic intracranial bleeding detected in control brain MRI.

Study protocol has been approved by the Ethics Committees in accordance with the principles and guidelines of the Declaration of Helsinki, 1975.

Conditions

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Coronary Artery Bypass Graft Redo Heart Valve Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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cardiac surgery with sonolysis

cardiac surgery (CABG or heart valve surgery) with sonolysis (continual transcranial Doppler monitoring)

Group Type EXPERIMENTAL

sonolysis

Intervention Type PROCEDURE

continual transcranial Doppler monitoring with max. diagnostic intensity for min. 60 minutes

cardiac surgery

Intervention Type PROCEDURE

coronary artery bypass graft (CABG) heart valve replacement

cardiac surgery without sonolysis

cardiac surgery (CABG or heart valve surgery) without sonolysis (continual transcranial Doppler monitoring)

Group Type PLACEBO_COMPARATOR

cardiac surgery

Intervention Type PROCEDURE

coronary artery bypass graft (CABG) heart valve replacement

Interventions

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sonolysis

continual transcranial Doppler monitoring with max. diagnostic intensity for min. 60 minutes

Intervention Type PROCEDURE

cardiac surgery

coronary artery bypass graft (CABG) heart valve replacement

Intervention Type PROCEDURE

Other Intervention Names

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sonothrombolysis sonothrombotripsy coronary artery bypass graft (CABG) heart valve replacement

Eligibility Criteria

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Inclusion Criteria

* age 40-90 years,
* sufficient temporal bone window for TCD with detectable blood flow in MCA,
* independent patient (modified Rankin score 0-2),
* informed consent signed by the patient,
* CS will be performed as an elective surgery with an extracorporeal circulation

Exclusion Criteria

* contra-indication for MRI examination (pace-maker, implanted metal material, claustrophobia),
* emergent surgery,
* acute myocardial infarction,
* combined cardiac surgery,
* combined cardiac and carotid surgery
Minimum Eligible Age

40 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Palacky University

OTHER

Sponsor Role collaborator

Ministry of Health, Czech Republic

OTHER_GOV

Sponsor Role collaborator

University Hospital Ostrava

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Skoloudik, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Ostrava

Locations

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University Hospital Ostrava

Ostrava, Czech Republic, Czechia

Site Status

Countries

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Czechia

References

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Skoloudik D, Hurtikova E, Brat R, Herzig R; SONORESCUE Trial Group. Sonolysis in Prevention of Brain Infarction During Cardiac Surgery (SONORESCUE): Randomized, Controlled Trial. Medicine (Baltimore). 2016 May;95(20):e3615. doi: 10.1097/MD.0000000000003615.

Reference Type DERIVED
PMID: 27196464 (View on PubMed)

Related Links

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http://fno.cz

University Hospital Ostrava

http://mzcr.cz

Ministry of Health of Czech Republic

Other Identifiers

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NT13498-4/2012

Identifier Type: -

Identifier Source: org_study_id