Sonolysis in Risk Reduction of Symptomatic and Silent Brain Infarctions During Coronary Stenting
Condition: Coronary Artery Disease
MeSH terms: Brain Infarction; Coronary Artery Disease; Infarction
Study type: Interventional

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 angioplasty
      and stenting of coronary arteries. 120 patients indicated for coronary angioplasty and
      stenting 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 cardiac endovascular treatment in 5% level of significance. Patients will be randomized
      - subgroup 1 will undergo a 40-240 minute non-diagnostic TCD monitoring during endovascular
      procedure, subgroup 2 will undergo interventions without TCD monitoring.

      Confirmation of our hypothesis that sonothrombolysis is able to activate endogenous
      fibrinolytic system during coronary angioplasty and stenting with consecutive reduction of
      the number and volume of brain infarcts, can lead to the increase of the safety these
      patients. We can presume that up to 50% of patients indicated for endovasular heart treatment
      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 coronary stenting.

      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 during sonothrombolysis (TCD monitoring) during coronary stenting 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.

      120 patients indicated for coronary stenting 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 procedure in 5% level of statistical
      significance. Patients will be randomized into 2 subgroups. Subgroup 1 will undergo
      non-diagnostic bilateral TCD monitoring during coronary stenting. Subgroup 2 will undergo
      coronary stenting without TCD monitoring.

      PATIENTS AND METHODS Patients: 120 patients indicated for coronary angioplasty and stenting
      will be enrolled into the study during a 3-year period. All 120 patients will be randomized
      for standard coronary angioplasty and stenting and TCD monitored.

      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 coronary angioplasty and stenting.

      Randomization: Randomization using computer generated random allocation will be used.

      Sonothrombolysis: In patients randomized into sonothrombolysis subgroup, bilateral 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 coronary angioplasty and stenting 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 in the all of
      brain territories.

      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.
    

Intervention name(s): Sonolysis; Sham procedure
Intervention type(s): Device; Other
Intervention description(s): continual transcranial Doppler monitoring of middle cerebral artery; sham transcranial Doppler monitoring of middle cerebral artery
Other intervention name(s): sonothrombolysis, sonothrombotripsy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention
Keywords: sonolysis, brain infarction, coronary angioplasty