Ischemic StrokePhase 3CE-5SNCT03290053
Contrast Enhanced Sonothrombolysis and Sonolysis in Stroke - a Swedish Study (CE-5S)
A Phase 3 study testing SonoVue, Sodium chloride and Transcranial Ultrasound in people with Ischemic Stroke, run by Umeå University at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- SonoVue, Sodium chloride and Transcranial Ultrasound
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteSweden
- Study dates
- 28 Nov 2017to 18 Apr 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
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- 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);
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- SonoVue, Sodium chloride, Transcranial Ultrasound, Sham Transcranial Ultrasound
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SonoVueDrug
SonoVue-infusion over 1 hour
Sodium chlorideDrug
Placebo
Transcranial UltrasoundProcedure or surgery
Transcranial ultrasound aimed at the blockage
Sham Transcranial UltrasoundProcedure or surgery
Placebo - machine is attached, but not active
| Study group | Role | What they receive |
|---|---|---|
| CE-5S A: Treatment arm | Experimental | Gets thrombolysis, transcranial ultrasound on the flow limitation and SonoVue infusion Receives: Drug: SonoVue; Procedure: Transcranial Ultrasound |
| CE-5S A: Control arm | Sham comparator | Gets thrombolysis, sham transcranial ultrasound and placebo (NaCl) infusion Receives: 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 Receives: 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 Receives: Drug: Sodium chloride; Procedure: Sham Transcranial Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours
Secondary outcomes (2)
Safety: Symptomatic Cerebral Hemorrhage (sICH)
Assessed with routine post-treatment CT head and requires an accompanied >=4 Points worsening on NIHSS.
Measured: 24-36 hours
Long term outcome defined as residual handicap at Three months
90-days modified Rankin Scale (mRS) reaching 0-1.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2017
- Study start28 Nov 2017
- Primary completion18 Apr 2018
- Study completion18 Apr 2018
Why it stopped: Poor inclusion rate \& lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Umeå UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Umeå University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elias Johansson, MD, PhD, Principal investigator, Umeå University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03290053
- Sponsor's protocol ID
- CE-5S
- Acronym
- CE-5S
- Status last verified
- Nov 2017
- First submitted
- 14 Sep 2017
- Last updated
- 11 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Contrast Enhanced Sonothrombolysis and Sonolysis in Stroke - a Swedish Study (CE-5S)
- ClinicalTrials.gov ID
- NCT03290053
- Acronym / sponsor ID
- CE-5S / CE-5S
- Conditions
- Ischemic Stroke
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor inclusion rate \& lack of funding
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Umeå UniversityUniversity, hospital or other
- Study start
- 28 Nov 2017 (actual)
- Primary completion
- 18 Apr 2018 (actual)
- Study completion
- 18 Apr 2018 (actual)
- First posted
- 21 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CE-5S A: Treatment arm | Experimental | Drug: SonoVue, Procedure: Transcranial UltrasoundGets thrombolysis, transcranial ultrasound on the flow limitation and SonoVue infusion |
| CE-5S A: Control arm | Sham comparator | Drug: Sodium chloride, Procedure: Sham Transcranial UltrasoundGets thrombolysis, sham transcranial ultrasound and placebo (NaCl) infusion |
| CE-5S B: Treatment arm | Experimental | Drug: SonoVue, Procedure: Transcranial UltrasoundGets NO thrombolysis (due to contraindications), transcranial ultrasound on the flow limitation and SonoVue infusion |
| CE-5S B: Control arm | Sham comparator | Drug: Sodium chloride, Procedure: Sham Transcranial UltrasoundGets NO thrombolysis (due to contraindications), sham transcranial ultrasound and placebo (NaCl) infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SonoVueSonoVue-infusion over 1 hour | Drug | CE-5S A: Treatment arm, CE-5S B: Treatment arm |
| Sodium chloridePlacebo | Drug | CE-5S A: Control arm, CE-5S B: Control arm |
| Transcranial UltrasoundTranscranial ultrasound aimed at the blockage | Procedure or surgery | CE-5S A: Treatment arm, CE-5S B: Treatment arm |
| Sham Transcranial UltrasoundPlacebo - machine is attached, but not active | Procedure or surgery | CE-5S A: Control arm, CE-5S B: Control arm |
Primary outcome
Early clinical Outcome defined as change in NIHSS at 24 hours.
Time frame: 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.
2 secondary outcomes
Safety: Symptomatic Cerebral Hemorrhage (sICH)
Time frame: 24-36 hours
Long term outcome defined as residual handicap at Three months
Time frame: 90 days
Results and safety
The study was stopped early (reason given: Poor inclusion rate \& lack of funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elias Johansson, MD, PhD principal investigator
Umeå University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SonoVue, Sodium chloride and Transcranial Ultrasound in people with Ischemic Stroke, run by Umeå University at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor inclusion rate \& lack of funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early clinical Outcome defined as change in NIHSS at 24 hours. (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2018.