NCT02398734

Brief Summary

SONOBIRDIE Trial is a randomized, single-blind, sham-controlled study designed for a demonstration of the safety and effectiveness of sonolysis (continual transcranial Doppler (TCD) monitoring) in reduction of risk of stroke or transient ischemic attack (TIA), brain infarctions and cognitive decline using a 2-MHz diagnostic probe with a maximal diagnostic energy on the reduction of risk of brain infarctions by the activation of endogenous fibrinolytic system during carotid endarterectomy (CEA) in patients with ≥ 70% symptomatic or asymptomatic internal carotid artery stenosis. The sample size is based on an expected 2.5% reduction of ischemic stroke, TIA, and death during the 30-day postoperative period in the sonolysis group (estimated prevalence, 1.5 %) compared to the control group (estimated prevalence, 4 %). Pre-study calculations showed that a minimum of 746 patients in each group is needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a beta value of 0.8 assuming that 10 % would be lost to follow-up or refuse to participate in the study. Consecutive patients will be assigned to the sonolysis or control group by a computer-generated 1:1 randomization. In patients randomized into sonolysis group, middle cerebral artery segment in a depth of 55 mm will be continuously monitored during intervention using a diagnostic 2-MHz TCD probe with a maximal diagnostic energy. In patients randomized into control group, the TCD probe will be fixed in a required position using a special helmet as in sonolysis group patients, but middle cerebral artery segment in a depth of 55 mm will be only localized using a diagnostic 2-MHz TCD probe with a maximal diagnostic energy and the TCD monitoring will be stopped afterwards. Confirmation of the investigators hypothesis that sonothrombolysis is able to activate endogenous fibrinolytic system during CEA with consecutive reduction of ischemic stroke, TIA or death, and the number and volume of brain infarcts, can lead to the increase of the safety of CEA in patients with internal carotid artery stenosis. The investigators can presume that up to 50% of patients indicated for CEA can be treated using these methods in the future.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,492

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Oct 2015

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 20, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 25, 2015

Completed
6 months until next milestone

Study Start

First participant enrolled

October 1, 2015

Completed
7.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2022

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2022

Completed
Last Updated

December 6, 2022

Status Verified

December 1, 2022

Enrollment Period

7.1 years

First QC Date

March 20, 2015

Last Update Submit

December 5, 2022

Conditions

Internal Carotid Artery Stenosis

Keywords

sonolysiscarotid endarterectomystroke preventionbrain infarction

Outcome Measures

Primary Outcomes (1)

  • Occurence of ischemic stroke, transient ischemic attack and death within 30 days

    The incidence of ischemic stroke, transient ischemic attack and death within 30 days in sonolysis and control groups

    30 days after randomization

Secondary Outcomes (13)

  • Occurrence of death within 30 days

    30 days after randomization

  • Occurrence of death within 1 year

    30 year after randomization

  • Occurrence of any stroke within 30 days

    30 days after randomization

  • Occurrence of myocardial infarction within 30 days

    30 days after randomization

  • Changes in cognitive functions within 1 year

    1 year after randomization

  • +8 more secondary outcomes

Other Outcomes (12)

  • Occurence of new ischemic lesions on brain DWI-MRI (Substudy)

    24 hours after intervention

  • Occurence of new ischemic lesions on brain DWI-MRI in local anesthesia and general anesthesia (Substudy)

    24 hours after intervention

  • Cosmetic outcome in patients after carotid endarterectomy using short longitudinal and transverse skin incision (Substudy)

    3 months after intervention

  • +9 more other outcomes

Study Arms (2)

Sonolysis

EXPERIMENTAL

In patients randomized into sonolysis group, middle cerebral artery segment in a depth of 55 mm will be continuously monitored during intervention using a diagnostic 2-MHz transcranial Doppler probe with a maximal diagnostic energy. The probe will be fixed in a required position using a special helmet and sonolysis will start before the carotid intervention and will be stopped after the intervention, but at latest after 120 minutes. Transcranial Doppler machine with a 2-MHz diagnostic transcranial Doppler probe will be used. This non-diagnostic transcranial Doppler monitoring will be performed without detection of microembolic signals or detection of changes in blood flow. Device sound and Doppler wave imaging will be switched off. Only sonographer will be unblinded to the procedure.

Device: sonolysis

Shame sonolysis

SHAM COMPARATOR

In patients randomized into control group, the transcranial Doppler probe will be fixed in a required position using a special helmet as in sonolysis group patients, but middle cerebral artery segment in a depth of 55 mm will be only localized using a diagnostic 2-MHz transcranial Doppler probe with a maximal diagnostic energy and the transcranial Doppler monitoring will be stopped afterwards. Patients in the control group will undergo a sham procedure in which further sonolysis (transcranial Doppler monitoring) will not be conducted.

Device: sonolysis

Interventions

sonolysisDEVICE

Continual transcranial Doppler monitoring of ipsilateral middle cerebral artery using a transcranial Doppler systems (e.g. DWL Multi-Dop T1, DWL, Sipplingen, Germany) with a diagnostic 2-MHz probe.

Also known as: sonothrombolysis
Shame sonolysisSonolysis

Eligibility Criteria

Age40 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subject has a symptomatic or asymptomatic ICA stenosis ≥ 70 % (NASCET criteria) as detected by a duplex sonography (see Appendix) and confirmed using the computed tomography angiography (CTA), magnetic resonance angiography (MRA) or digital subtraction angiography (DSA).
  • Subject is indicated for CEA according to the criteria set by the American Heart Association.
  • Subject is aged 40 - 85 years.
  • Subject has a sufficient temporal bone window for TCD with detectable blood flow in the MCA.
  • Subject is functionally independent with a modified Rankin score value of 0 - 2 points.
  • Informed consent is signed by the subject.

You may not qualify if:

  • Subject has been participating in another clinical trial within last 6 weeks.
  • Subject has any other medical condition that would make him/her inappropriate for study participation, in the Investigator opinion.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Ostrava

Ostrava, Czech Republic, 70852, Czechia

Location

Related Publications (3)

  • Hrbac T, Netuka D, Benes V, Nosal V, Kesnerova P, Tomek A, Fadrna T, Benes V Jr, Fiedler J, Priban V, Brozman M, Langova K, Herzig R, Skoloudik D. SONOlysis in prevention of Brain InfaRctions During Internal carotid Endarterectomy (SONOBIRDIE) trial - study protocol for a randomized controlled trial. Trials. 2017 Jan 17;18(1):25. doi: 10.1186/s13063-016-1754-x.

    PMID: 28095924BACKGROUND

  • Skoloudik D, Hrbac T, Kovar M, Benes V 3rd, Fiedler J, Branca M, Rossel JB, Netuka D; SONOBIRDIE Trial Investigators. Sonolysis during carotid endarterectomy: randomised controlled trial. BMJ. 2025 Mar 19;388:e082750. doi: 10.1136/bmj-2024-082750.

    PMID: 40107675DERIVED

  • Orlicky M, Hrbac T, Sames M, Vachata P, Hejcl A, Otahal D, Havelka J, Netuka D, Herzig R, Langova K, Skoloudik D. Anesthesia type determines risk of cerebral infarction after carotid endarterectomy. J Vasc Surg. 2019 Jul;70(1):138-147. doi: 10.1016/j.jvs.2018.10.066. Epub 2019 Feb 18.

    PMID: 30792052DERIVED

MeSH Terms

Conditions

Carotid StenosisBrain Infarction

Condition Hierarchy (Ancestors)

Carotid Artery DiseasesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesArterial Occlusive DiseasesVascular DiseasesCardiovascular DiseasesBrain IschemiaStrokeInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosis

Study Officials

  • David Skoloudik, MD,PhD,FESO

    Department of Neurology, University Hospital Ostrava

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 20, 2015

First Posted

March 25, 2015

Study Start

October 1, 2015

Primary Completion

November 1, 2022

Study Completion

December 1, 2022

Last Updated

December 6, 2022

Record last verified: 2022-12

Data Sharing

IPD Sharing
Will share

The IPD sharing plan will be created prior to publication of study results.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
The data will become available after publication for 10 years.
Access Criteria
The IPD sharing access criteria will be created prior to publication of study results.

Locations

CZ(1)