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

Phase 3

Terminated

• Conditions: Ischemic Stroke
• Interventions: Drug: SonoVue; Drug: Sodium chloride; Procedure: Transcranial Ultrasound; Procedure: Sham Transcranial Ultrasound

• Registration Number: NCT03290053
• Lead Sponsor: Umeå University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-09-14
• Study First Submitted QC: 2017-09-20
• Study First Posted: 2017-09-21
• Status Verified: 2017-11
• Study Start: 2017-11-28
• Primary Completion: 2018-04-18
• Study Completion: 2018-04-18
• Last Update Submitted: 2018-05-04
• Last Update Posted: 2018-05-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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.

Specific sonothrombolysis exclusion criteria

• 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);

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CE-5S A: Treatment arm	SonoVue	Gets thrombolysis, transcranial ultrasound on the flow limitation and SonoVue infusion
CE-5S A: Control arm	Sodium chloride	Gets thrombolysis, sham transcranial ultrasound and placebo (NaCl) infusion
CE-5S A: Treatment arm	Transcranial Ultrasound	Gets thrombolysis, transcranial ultrasound on the flow limitation and SonoVue infusion
CE-5S B: Treatment arm	Transcranial Ultrasound	Gets NO thrombolysis (due to contraindications), transcranial ultrasound on the flow limitation and SonoVue infusion
CE-5S B: Control arm	Sham Transcranial Ultrasound	Gets NO thrombolysis (due to contraindications), sham transcranial ultrasound and placebo (NaCl) infusion
CE-5S A: Control arm	Sham Transcranial Ultrasound	Gets thrombolysis, sham transcranial ultrasound and placebo (NaCl) infusion
CE-5S B: Treatment arm	SonoVue	Gets NO thrombolysis (due to contraindications), transcranial ultrasound on the flow limitation and SonoVue infusion
CE-5S B: Control arm	Sodium chloride	Gets NO thrombolysis (due to contraindications), sham transcranial ultrasound and placebo (NaCl) infusion

Primary Outcome Measures

Name	Time	Method
Early clinical Outcome defined as change in NIHSS at 24 hours.	24 hours	Change in National NIHSS at 24 hours. Defined reaching of primary endpoint is post-treatment 0 Points and/or improves with \>=4 Points compared to pre-treatment.

Secondary Outcome Measures

Name	Time	Method
Safety: Symptomatic Cerebral Hemorrhage (sICH)	24-36 hours	Assessed with routine post-treatment CT head and requires an accompanied \>=4 Points worsening on NIHSS.
Long term outcome defined as residual handicap at Three months	90 days	90-days modified Rankin Scale (mRS) reaching 0-1.

Trial Locations

Locations (1)

University Hospital; 🇸🇪 Umeå, Västerbotten, Sweden