Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01591018 |
| Other study ID # |
NT13498-4/2012 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
September 2012 |
| Est. completion date |
July 2015 |
Study information
| Verified date |
October 2020 |
| Source |
University Hospital Ostrava |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
