Contrast Enhanced Sonothrombolysis and Sonolysis in Stroke - a Swedish Study (CE-5S)

NCT ID: NCT03290053

Last Updated: 2018-05-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-28
• Study Completion Date: 2018-04-18

Brief Summary

Patients with acute ischemic stroke in anterior circulation within 4,5 hours of symptom onset, has a bone window and Trombolysis In Brain Ischemia (TIBI) <=4 in a relevant artery eligible. Both patients receiving thrombolysis and those who do not due to contraindications such as anticoagulation or recent surgery are enrolled, but into different study arms (CE-5S A for thrombolysis and B for non-thrombolysis); the decision to treat with thrombolysis or not is done according to clinical routine.

All included patients are randomized to receive transcranial ultrasound and SonoVue-infusion or sham-ultrasound and placebo; i.e. in CE-5S A, contrast enhanced sonothrombolysis is compared to thrombolysis and in CE-5S B, contrast enhanced sonolysis is compared with conservative management.

Main outcome is improvement in National Institute of Health Stroke Scale (NIHSS) at 24 hours compared to baseline. Main safety outcome is symptomatic intracerebral haemorrhage.

Conditions

Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

CE-5S A: Treatment arm

Gets thrombolysis, transcranial ultrasound on the flow limitation and SonoVue infusion

Group Type: EXPERIMENTAL

SonoVue

Intervention Type: DRUG

SonoVue-infusion over 1 hour

Transcranial Ultrasound

Intervention Type: PROCEDURE

Transcranial ultrasound aimed at the blockage

CE-5S A: Control arm

Gets thrombolysis, sham transcranial ultrasound and placebo (NaCl) infusion

Group Type: SHAM_COMPARATOR

Sodium chloride

Intervention Type: DRUG

Placebo

Sham Transcranial Ultrasound

Intervention Type: PROCEDURE

Placebo - machine is attached, but not active

CE-5S B: Treatment arm

Gets NO thrombolysis (due to contraindications), transcranial ultrasound on the flow limitation and SonoVue infusion

Group Type: EXPERIMENTAL

SonoVue

Intervention Type: DRUG

SonoVue-infusion over 1 hour

Transcranial Ultrasound

Intervention Type: PROCEDURE

Transcranial ultrasound aimed at the blockage

CE-5S B: Control arm

Gets NO thrombolysis (due to contraindications), sham transcranial ultrasound and placebo (NaCl) infusion

Group Type: SHAM_COMPARATOR

Sodium chloride

Intervention Type: DRUG

Placebo

Sham Transcranial Ultrasound

Intervention Type: PROCEDURE

Placebo - machine is attached, but not active

Interventions

SonoVue

SonoVue-infusion over 1 hour

Intervention Type: DRUG

Sodium chloride

Placebo

Intervention Type: DRUG

Transcranial Ultrasound

Transcranial ultrasound aimed at the blockage

Intervention Type: PROCEDURE

Sham Transcranial Ultrasound

Placebo - machine is attached, but not active

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Male or female patients ≥18 years with acute ischaemic stroke in the anterior circulation, who has given written consent for his/her participation to the study.
• Remaining neurological deficit that is ≥1 NIHSS points, sufficient to warrant treatment with tPA (not taking possible contraindications into account) and is severe enough that possible improvement is clearly analysable
• Treatment <4½ hours of symptom onset or of waking up in the morning with symptoms
• Sufficient bone window for acceptable or better acquisition of flow information with ultrasound with TIBI ≤ 4 in the symptomatic artery
• In cases with women of Childbearing Capacity (WOCBC): Only if willing to comply with effective contraception methods during the course of the trial. Acceptable methods are such as oral contraceptives, contraceptive patches, contraceptive implant, vaginal contraceptive, double-barrier methods (for example, condom and spermicide), intrauterine device (IUD), hormonal IUD

Exclusion Criteria

• Patients with premorbid modified Rankin Scale (mRS) score ≥3;
• Patients for whom a complete NIHSS cannot be obtained;
• Hemiplegic migraine with no arterial occlusion on baseline Computed Tomography of brain (CT);
• Seizure at stroke onset and no visible occlusion on baseline CT;
• Intracranial haemorrhage on baseline CT;
• Clinical presentation suggesting subarachnoid haemorrhage even if baseline CT is normal;
• Large areas of hypodense ischaemic changes on baseline CT;
• Pregnancy or breast-feeding, pericarditis; sepsis; any other serious medical illness likely to interact with treatment; confounding pre-existent neurological or psychiatric disease; unlikely to complete follow-up; any investigational drug <14 days;
• Inability to provide informed consent sufficiently clearly that the study physician can be convinced that informed consent has been given by the patient - such as severe aphasia or coma.

• known hypersensitivity/allergy to SonoVue;
• recent or unstable coronary ischemia or resting angina <7 days;
• acute cardiac insufficiency, cardiac insufficiency class III/IV; serious cardiac arrhythmias;
• any right-left-shunt; severe pulmonary hypertension; uncontrolled hypertension;
• moderate to severe Chronic Obstructive Pulmonary Disease (COPD; baseline O2 saturation <80%);
• acute respiratory distress syndrome (ARDS);

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Umeå University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elias Johansson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Umeå University

Locations

University Hospital

Umeå, Västerbotten County, Sweden

Countries

Sweden

Other Identifiers

CE-5S

Identifier Type: -

Identifier Source: org_study_id