- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02351050
Sonolysis in Risk Reduction of Symptomatic and Silent Brain Infarctions During Coronary Stenting
Sonolysis in Risk Reduction of Symptomatic and Silent Brain Infarctions During Coronary Stenting Due to Ultrasound Activation of Endogenous Fibrinolytic System Using Transcranial Doppler Monitoring
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Nitra, Slovakia, 70852
- University Hospital Nitra
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- age 35-90 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
- coronary angioplasty and stenting will be performed as an elective procedure
Exclusion Criteria:
- contra-indication for MRI examination (pace-maker, implanted metal material, claustrophobia)
- emergent coronary angioplasty and stenting
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Sonolysis
continual transcranial Doppler monitoring with maximal intensity during endovascular procedure
|
continual transcranial Doppler monitoring of middle cerebral artery
Other Names:
|
Placebo Comparator: placebo
sham transcranial Doppler monitoring during endovascular procedure
|
sham transcranial Doppler monitoring of middle cerebral artery
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
New infarction
Time Frame: 24 hours after intervention
|
New brain infarction detected using magnetic resonance diffusion weighted images (MRI-DWI)
|
24 hours after intervention
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cognitive functions changes, measured by ADAS, MMSE, Clock Drawing Test and Verbal Fluency Test
Time Frame: 7 and 30 days after interventions
|
Cognitive decline measured by ADAS, MMSE, Clock Drawing Test and Verbal Fluency Test
|
7 and 30 days after interventions
|
Large new infarction, infarction ≥0.5 mL detected using magnetic resonance diffusion weighted images (MRI-DWI)
Time Frame: 24 hours after intervention
|
New brain infarction ≥0.5 mL detected using magnetic resonance diffusion weighted images (MRI-DWI)
|
24 hours after intervention
|
Volume of new brain infarction, detected using magnetic resonance diffusion weighted images (MRI-DWI)
Time Frame: 24 hours after intervention
|
Volume of new brain infarctions detected using magnetic resonance diffusion weighted images (MRI-DWI)
|
24 hours after intervention
|
30-days morbidity and mortality
Time Frame: 30 days after intervention
|
stroke, TIA, myocardial infarctions and death during 30 days after intervention
|
30 days after intervention
|
Symptomatic intracerebral hemorrhage, detected using magnetic resonance (MRI)
Time Frame: 24 hours after intervention
|
Intracerebral hemorrhage with worsening of neurological status (≥ 4 points in NIHSS scale) detected using magnetic resonance (MRI)
|
24 hours after intervention
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: David Skoloudík, MD, Prof, University Hospital Ostrava
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Ischemia
- Pathologic Processes
- Necrosis
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Brain Ischemia
- Coronary Disease
- Stroke
- Infarction
- Coronary Artery Disease
- Brain Infarction
Other Study ID Numbers
- 13595
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Coronary Artery Disease
-
Elixir Medical CorporationIstituto Clinico HumanitasActive, not recruitingCoronary Artery Disease | Chronic Total Occlusion of Coronary Artery | Multi Vessel Coronary Artery Disease | Bifurcation of Coronary Artery | Long Lesions Coronary Artery DiseaseItaly
-
Fundación EPICActive, not recruitingCoronary Artery Disease | Left Main Coronary Artery Disease | Left Main Coronary Artery Stenosis | Restenosis, CoronarySpain
-
Peking Union Medical College HospitalNot yet recruitingCoronary Artery Disease | Inflammation | Coronary Artery Disease Progression | Coronary Artery Stenosis | Coronary Artery Restenosis | Inflammatory Disease | Inflammation VascularChina
-
Peking Union Medical College HospitalRecruitingCoronary Artery Disease | Inflammation | Coronary Artery Disease Progression | Coronary Artery Stenosis | Coronary Artery Restenosis | Inflammatory Disease | Inflammation VascularChina
-
IGLESIAS Juan FernandoUniversity of BernNot yet recruiting
-
National Institutes of Health Clinical Center (CC)National Heart, Lung, and Blood Institute (NHLBI)CompletedCoronary Arteriosclerosis | Coronary Artery Disease (CAD) | Obstructive Coronary Artery DiseaseUnited States
-
Barts & The London NHS TrustImperial College London; Brunel UniversityNot yet recruitingCORONARY ARTERY DISEASE
-
Fundación EPICRecruitingCoronary Artery Disease | Coronary Disease | Coronary Occlusion | Left Main Coronary Artery Disease | Coronary Artery StenosisSpain
-
Abbott Medical DevicesCompletedCoronary Artery Disease | Coronary Disease | Coronary Occlusion | Chronic Total Occlusion of Coronary Artery | Coronary Restenosis | Coronary Artery Stenosis | Coronary Artery RestenosisBelgium
-
China National Center for Cardiovascular DiseasesRecruitingLeft Main Coronary Artery DiseaseChina
Clinical Trials on Sonolysis
-
Charite University, Berlin, GermanyBerlin Institute of HealthRecruitingMitral Valve InsufficiencyGermany
-
University Hospital OstravaÚstřední fakultní vojenská nemocnice, Praha, Czechia; Vítkovická nemocnice,... and other collaboratorsCompletedInternal Carotid Artery StenosisCzechia
-
University Hospital OstravaPalacky University; Ministry of Health, Czech RepublicCompletedHeart Valve Diseases | Coronary Artery Bypass Graft RedoCzechia
-
University Hospital OstravaPalacky UniversityCompletedInternal Carotid Artery StenosisCzech Republic
-
Cerevast Medical, Inc.UnknownAcute Ischemic StrokeUnited States