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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01591018
Recruitment Status : Completed
First Posted : May 3, 2012
Results First Posted : September 8, 2016
Last Update Posted : September 8, 2016
Sponsor:
Collaborators:
Palacky University
Ministry of Health, Czech Republic
Information provided by (Responsible Party):
University Hospital Ostrava

Tracking Information
First Submitted Date  ICMJE April 23, 2012
First Posted Date  ICMJE May 3, 2012
Results First Submitted Date  ICMJE July 24, 2016
Results First Posted Date  ICMJE September 8, 2016
Last Update Posted Date September 8, 2016
Study Start Date  ICMJE September 2012
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2016)
Number od Participants With New Brain Infarction in the Monitored MCA Territory Detected Using MRI [ Time Frame: 24 hours after intervention ]
to demonstrate a twenty-percent risk reduction of number and volume of brain infarctions and brain infarctions > 0.5 cm3 in the monitored MCA territory in sonolysis group detected using MRI examination 24 hours after cardiac surgery in 5% level of statistical significance
Original Primary Outcome Measures  ICMJE
 (submitted: May 2, 2012)
New brain infarction detected using MRI [ Time Frame: 24 hours after intervention ]
to demonstrate a twenty-percent risk reduction of number and volume of brain infarctions and brain infarctions > 0.5 cm3 in sonolysis group detected using MRI examination 24 hours after cardiac surgery in 5% level of statistical significance
Change History Complete list of historical versions of study NCT01591018 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2016)
  • Cognitive Decline [ Time Frame: 30 days after intervention ]
    To demonstrate an effect of sonolysis on the reduction of cognitive decline after cardiac surgery measured by ACE-R. Adenbook´s cognitive examination - revised (ACE-R) can aquire value 0 to 100. Higher value represents better cognitive functions.
  • Number of Participants With Clinical Manifested Brain Infarction [ Time Frame: 30 days after intervention ]
    to demonstrate an effect of sonolysis on the reduction of risk of clinically stroke due to the activation of endogenous fibrinolytic system during cardiac surgery
Original Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2012)
  • Cognitive Decline [ Time Frame: 7 and 30 days after intervention ]
    to demonstrate an effect of sonolysis on the reduction of cognitive decline after cardiac surgery measured by ADAS, MMSE, Clock Drawing Test and Verbal Fluency Test
  • Clinical manifested brain infarction [ Time Frame: 24 hours and 30 days after intervention ]
    to demonstrate an effect of sonolysis on the reduction of risk of clinically stroke due to the activation of endogenous fibrinolytic system during cardiac surgery
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SONOlysis in Risk REduction of Symptomatic and Silent Brain infarCtions dUring Cardiac surgEry
Official Title  ICMJE Risk Reduction of Symptomatic and Silent Brain Infarctions During Cardiac Surgery Due to Ultrasound Activation of Endogenous Fibrinolytic System Using Transcranial Doppler Monitoring
Brief Summary

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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Coronary Artery Bypass Graft Redo
  • Heart Valve Diseases
Intervention  ICMJE
  • Procedure: sonolysis
    continual transcranial Doppler monitoring with max. diagnostic intensity for min. 60 minutes
    Other Names:
    • sonothrombolysis
    • sonothrombotripsy
  • Procedure: cardiac surgery
    coronary artery bypass graft (CABG) heart valve replacement
    Other Names:
    • coronary artery bypass graft (CABG)
    • heart valve replacement
Study Arms  ICMJE
  • Experimental: cardiac surgery with sonolysis
    cardiac surgery (CABG or heart valve surgery) with sonolysis (continual transcranial Doppler monitoring)
    Interventions:
    • Procedure: sonolysis
    • Procedure: cardiac surgery
  • Placebo Comparator: cardiac surgery without sonolysis
    cardiac surgery (CABG or heart valve surgery) without sonolysis (continual transcranial Doppler monitoring)
    Intervention: Procedure: cardiac surgery
Publications * Školoudík D, Hurtíková E, Brát 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 2, 2012)
120
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2015
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czech Republic
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01591018
Other Study ID Numbers  ICMJE NT13498-4/2012
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party University Hospital Ostrava
Study Sponsor  ICMJE University Hospital Ostrava
Collaborators  ICMJE
  • Palacky University
  • Ministry of Health, Czech Republic
Investigators  ICMJE
Principal Investigator: David Skoloudik, MD, PhD University Hospital Ostrava
PRS Account University Hospital Ostrava
Verification Date August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP