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

NCT03290053 | Terminated Phase 3 DMC

• 1 other identifier: CE-5S
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Early clinical Outcome defined as change in NIHSS at 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.

  24 hours

Secondary Outcomes (2)

• Safety: Symptomatic Cerebral Hemorrhage (sICH)

  24-36 hours

• Long term outcome defined as residual handicap at Three months

  90 days

Study Arms (4)

CE-5S A: Treatment arm

EXPERIMENTAL

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

Drug: SonoVue; Procedure: Transcranial Ultrasound

CE-5S A: Control arm

SHAM COMPARATOR

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

Drug: Sodium chloride; Procedure: Sham Transcranial Ultrasound

CE-5S B: Treatment arm

EXPERIMENTAL

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

Drug: SonoVue; Procedure: Transcranial Ultrasound

CE-5S B: Control arm

SHAM COMPARATOR

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

Drug: Sodium chloride; Procedure: Sham Transcranial Ultrasound

Interventions

SonoVue DRUG

SonoVue-infusion over 1 hour

CE-5S A: Treatment arm; CE-5S B: Treatment arm

Sodium chloride DRUG

Placebo

CE-5S A: Control arm; CE-5S B: Control arm

Transcranial Ultrasound PROCEDURE

Transcranial ultrasound aimed at the blockage

CE-5S A: Treatment arm; CE-5S B: Treatment arm

Sham Transcranial Ultrasound PROCEDURE

Placebo - machine is attached, but not active

CE-5S A: Control arm; CE-5S B: Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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);

Sponsors & Collaborators

• Umeå University: lead

Study Sites (1)

University Hospital

Umeå, Västerbotten County, 90821, Sweden

Location

MeSH Terms

Conditions

Ischemic Stroke

Interventions

contrast agent BR1; Sodium Chloride

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Elias Johansson, MD, PhD

  Umeå University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: September 21, 2017
• Study Start: November 28, 2017
• Primary Completion: April 18, 2018
• Study Completion: April 18, 2018
• Last Updated: May 11, 2018

Record last verified: 2017-11

Locations

SE (1)