Ischemic StrokeNOR-SASS 2NCT01949961
The Norwegian Sonothrombolysis in Acute Stroke Study Part 2
A study testing Ultrasound in people with Ischemic Stroke, run by Haukeland University Hospital at 1 site in Norway.
Trial summary
BACKGROUND: Thrombolytic drugs may dissolve blood vessel clots in acute ischemic stroke. The overall benefit of intravenous thrombolysis is substantial, but up to 2/3 of patients with large clots may not achieve re-opening of the vessel and up to 40% of the patients may remain severely disabled or die. 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?
- Ultrasound
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 1 siteNorway
- Study dates
- Jan 2016to 31 Dec 2019
- Phase
- Interventional
- 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
- Ischemic stroke in the anterior circulation
- Treatment within 4.5 hours after stroke onset
- Informed consent
Who cannot join
- Patients with premorbid modified Rankin Scale (mRS) score ≥3;
- Patients for whom a complete NIH Stroke Score cannot be obtained;
- Hemiplegic migraine with no arterial occlusion on baseline CT;
- Seizure at stroke onset and no visible occlusion on baseline CT;
- Intracranial haemorrhage on baseline CT;
- Clinical subarachnoid haemorrhage even if baseline CT is normal;
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- Large areas of hypodense ischaemic changes on baseline CT;
- Patients with primary endovascular treatment;
- Female, pregnant 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;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomised Trial of Contrast-enhanced Sonothrombolysis in Acute Ischaemic Stroke
BACKGROUND: Thrombolytic drugs may dissolve blood vessel clots in acute ischemic stroke. The overall benefit of intravenous thrombolysis is substantial, but up to 2/3 of patients with large clots may not achieve re-opening of the vessel and up to 40% of the patients may remain severely disabled or die. Ultrasound accelerates clot break-up (lysis) when combined with thrombolysis (sonothrombolysis) and increases the likelihood of functional independence at 3 months. Adding intravenous ultrasound contrast (gaseous microspheres) further enhances the thrombolytic effect (contrast enhanced sonothrombolysis = CEST). Contrast enhanced ultrasound may also accelerate clot break-up in the absence of thrombolytic drugs (contrast enhanced sonolysis = CES).
HYPOTHESIS: Contrast enhanced ultrasound treatment administered within 4 1/2 hours after symptom onset may be given safely to patients with acute ischemic stroke, both to those receiving intravenous thrombolysis and those not receiving intravenous thrombolysis, and will improve clinical outcome.
Read more
AIMS: To compare efficacy and safety of contrast enhanced ultrasound treatment vs. no ultrasound treatment in patients with acute ischemic stroke receiving or not receiving intravenous thrombolysis.
STUDY ENDPOINTS: The primary endpoints are 1) neurological improvement at 24 hours (proof of concept) and 2) excellent clinical outcome at 3 months (effect). Secondary endpoints are bleeding complications (safety), brain damage (infarct size/location) and early clinical improvement (effect).
Read the detailed description
NOR-SASS aims at testing contrast enhanced sonothrombolysis in all patients with acute ischemic stroke. Patients eligible for thrombolysis (randomized tenecteplase or alteplase) are included in the NOR-SASS A sub-study, patients receiving standard (non-trial) thrombolysis with alteplase are included in the NOR-SASS B sub-study, and patients not eligible for thrombolysis are included in the NOR-SASS C sub-study.
DESIGN: NOR-SASS is a PROBE (prospective randomised, open-label, blinded endpoint) trial, designed to establish the superiority of contrast-enhanced ultrasound treatment given within 4½ hours after stroke onset in consecutively admitted patients with acute ischaemic stroke, as compared with 1) standard iv thrombolysis with tenecteplase (TNK) or alteplase (tPA) in patients eligible for thrombolytic treatment, and 2) no specific treatment in patients not eligible for thrombolytic treatment.
HYPOTHESIS: 1.) In patients eligible for intravenous thrombolysis, contrast enhanced sonothrombolysis (CEST) has superior effect as compared with standard intravenous thrombolysis and may be given safely. 2.) In patients not eligible for thrombolysis, contrast enhanced sonolysis (CES) has superior effect as compared with no specific treatment and may be given safely.
RANDOMISATION: In NOR-SASS-A (two step randomisation), 1st randomisation is 1:1 to either tenecteplase (TNK) or alteplase (tPA); 2nd randomisation is 1:1 to either CEST or no CEST. In NOR-SASS-B, randomisation is 1:1 to either CEST or no CEST. In NOR-SASS-C, randomisation is 1:1 to either CES or no CES.
- Conditions
- Ischemic Stroke
- Being tested
- Ultrasound, Sham ultrasound
- Keywords
- intervention, sonothrombolysis, Ultrasound treatment
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UltrasoundOther
SonoVue solution 10 ml (2 vials / 80 µl microbubbles) is given as an infusion of 0,3 ml/min for ~30 minutes, using a Bracco infusion pump.
Sham ultrasoundOther
Mounting the ultrasound headframe but connecting this to a non-operative channel
| Study group | Role | What they receive |
|---|---|---|
| Ultrasound | Active comparator | Patients eligible (NOR-SASS A/B) and ineligible (NOR-SASS C) for intravenous thrombolysis all receive intravenous ultrasound contrast (microbubbles). The groups are separately randomised to 2 megahertz (MHz) transcranial ultrasound treatment for one hour. Receives: Other: Ultrasound |
| Sham ultrasound | Placebo comparator | Patients eligible (NOR-SASS A/B) and ineligible (NOR-SASS C) for intravenous thrombolysis all receive intravenous ultrasound contrast (microbubbles). The two groups are separately randomised to sham ultrasound treatment for one hour. Receives: Other: Sham ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical: Functional handicap
Sliding dichotomy/responder analysis: Excellent outcome is defined as modified Rankin Scale (mRS) 0 with baseline National Institutes of Health Stroke Scale (NIHSS), as mRS 0-1 with baseline NIHSS 8-14, as mRS 0-2 with baseline NIHSS ≥15
Measured: 90 days
Proof of concept: Early neurological improvement
NIHSS=0 or reduction of ≥4 NIHSS points compared with baseline
Measured: 22-36 hours
Secondary outcomes (4)
Symptomatic intracerebral hemorrhage
Local or remote parenchymal haemorrhage type 2 on the 22-36 h post-treatment imaging scan, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline or from the lowest NIHSS value between baseline and 24 h, or leading to death (SITS-MOST criteria).
Measured: 24-36 hours
Hemorrhagic transformation
Any hemorrhagic changes (infarct or parenchymal hematoma)
Measured: 24-36 hours
Short term functional outcome
Sliding dichotomy/responder analysis: Excellent outcome is defined as mRS 0 with baseline NIHSS ≤7, as mRS 0-1 with baseline NIHSS 8-14, as mRS 0-2 with baseline NIHSS ≥15
Measured: 7 days
Brain infarct size and location
MRI infarct volume and ASPECTS score
Measured: 22-36 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2013 (estimated)
- Study startJan 2016
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Why it stopped: Lack of funding for researchers
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- PROBE: Prospective randomized open-label blinded-endpoint
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bergen, Sykehuset Telemark
- Responsible party
- Sponsor
- Investigators
- Lars Thomassen, MD PhD Prof., Study director, Dept. Neurology, Haukeland University Hospital, Bergen, NorwayChristopher E Kvistad, MD, Study chair, Dept. Neurology, Haukeland University Hospital, Bergen, NorwayHaakon Tobro, MD, Principal investigator, Dept. Neurology, Sykehuset Telemark, Skien
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01949961
- Sponsor's protocol ID
- REK 2011/2448
- Other IDs
- 2012-000323-41
- Acronym
- NOR-SASS 2
- Status last verified
- Aug 2018
- First submitted
- 21 Sep 2013
- Last updated
- 15 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nacu A, Kvistad CE, Logallo N, Naess H, Waje-Andreassen U, Aamodt AH, Solhoff R, Lund C, Tobro H, Ronning OM, Salvesen R, Idicula TT, Thomassen L. A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS). BMC Neurol. 2015 Jul 11;15:110. doi: 10.1186/s12883-015-0359-4.
PubMed 26162826Nacu A, Kvistad CE, Naess H, Oygarden H, Logallo N, Assmus J, Waje-Andreassen U, Kurz KD, Neckelmann G, Thomassen L. NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): Randomized Controlled Contrast-Enhanced Sonothrombolysis in an Unselected Acute Ischemic Stroke Population. Stroke. 2017 Feb;48(2):335-341. doi: 10.1161/STROKEAHA.116.014644. Epub 2016 Dec 15.
PubMed 27980128
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Trial of Contrast-enhanced Sonothrombolysis in Acute Ischaemic Stroke
- ClinicalTrials.gov ID
- NCT01949961
- Acronym / sponsor ID
- NOR-SASS 2 / REK 2011/2448
- Conditions
- Ischemic Stroke
- Keywords
- intervention, sonothrombolysis, Ultrasound treatment
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding for researchers
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Collaborators
- University of Bergen, Sykehuset Telemark
- Study start
- Jan 2016 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 25 Sep 2013 (estimated)
- 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.
BACKGROUND: Thrombolytic drugs may dissolve blood vessel clots in acute ischemic stroke. The overall benefit of intravenous thrombolysis is substantial, but up to 2/3 of patients with large clots may not achieve re-opening of the vessel and up to 40% of the patients may remain severely disabled or die. Ultrasound accelerates clot break-up (lysis) when combined with thrombolysis (sonothrombolysis) and increases the likelihood of functional independence at 3 months. Adding intravenous ultrasound contrast (gaseous microspheres) further enhances the thrombolytic effect (contrast enhanced sonothrombolysis = CEST). Contrast enhanced ultrasound may also accelerate clot break-up in the absence of thrombolytic drugs (contrast enhanced sonolysis = CES).
HYPOTHESIS: Contrast enhanced ultrasound treatment administered within 4 1/2 hours after symptom onset may be given safely to patients with acute ischemic stroke, both to those receiving intravenous thrombolysis and those not receiving intravenous thrombolysis, and will improve clinical outcome.
AIMS: To compare efficacy and safety of contrast enhanced ultrasound treatment vs. no ultrasound treatment in patients with acute ischemic stroke receiving or not receiving intravenous thrombolysis.
STUDY ENDPOINTS: The primary endpoints are 1) neurological improvement at 24 hours (proof of concept) and 2) excellent clinical outcome at 3 months (effect). Secondary endpoints are bleeding complications (safety), brain damage (infarct size/location) and early clinical improvement (effect).
Detailed description
NOR-SASS aims at testing contrast enhanced sonothrombolysis in all patients with acute ischemic stroke. Patients eligible for thrombolysis (randomized tenecteplase or alteplase) are included in the NOR-SASS A sub-study, patients receiving standard (non-trial) thrombolysis with alteplase are included in the NOR-SASS B sub-study, and patients not eligible for thrombolysis are included in the NOR-SASS C sub-study.
DESIGN: NOR-SASS is a PROBE (prospective randomised, open-label, blinded endpoint) trial, designed to establish the superiority of contrast-enhanced ultrasound treatment given within 4½ hours after stroke onset in consecutively admitted patients with acute ischaemic stroke, as compared with 1) standard iv thrombolysis with tenecteplase (TNK) or alteplase (tPA) in patients eligible for thrombolytic treatment, and 2) no specific treatment in patients not eligible for thrombolytic treatment.
HYPOTHESIS: 1.) In patients eligible for intravenous thrombolysis, contrast enhanced sonothrombolysis (CEST) has superior effect as compared with standard intravenous thrombolysis and may be given safely. 2.) In patients not eligible for thrombolysis, contrast enhanced sonolysis (CES) has superior effect as compared with no specific treatment and may be given safely.
RANDOMISATION: In NOR-SASS-A (two step randomisation), 1st randomisation is 1:1 to either tenecteplase (TNK) or alteplase (tPA); 2nd randomisation is 1:1 to either CEST or no CEST. In NOR-SASS-B, randomisation is 1:1 to either CEST or no CEST. In NOR-SASS-C, randomisation is 1:1 to either CES or no CES.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- PROBE: Prospective randomized open-label blinded-endpoint
| Arm | Type | Receives |
|---|---|---|
| Ultrasound | Active comparator | Other: UltrasoundPatients eligible (NOR-SASS A/B) and ineligible (NOR-SASS C) for intravenous thrombolysis all receive intravenous ultrasound contrast (microbubbles). The groups are separately randomised to 2 megahertz (MHz) transcranial ultrasound treatment for one hour. |
| Sham ultrasound | Placebo comparator | Other: Sham ultrasoundPatients eligible (NOR-SASS A/B) and ineligible (NOR-SASS C) for intravenous thrombolysis all receive intravenous ultrasound contrast (microbubbles). The two groups are separately randomised to sham ultrasound treatment for one hour. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Ischemic stroke in the anterior circulation
- Treatment within 4.5 hours after stroke onset
- Informed consent
Key exclusion criteria (9 listed)
- Patients with premorbid modified Rankin Scale (mRS) score ≥3;
- Patients for whom a complete NIH Stroke Score cannot be obtained;
- Hemiplegic migraine with no arterial occlusion on baseline 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 |
|---|---|---|
| UltrasoundSonoVue solution 10 ml (2 vials / 80 µl microbubbles) is given as an infusion of 0,3 ml/min for ~30 minutes, using a Bracco infusion pump. | Other | Ultrasound |
| Sham ultrasoundMounting the ultrasound headframe but connecting this to a non-operative channel | Other | Sham ultrasound |
Primary outcome
Clinical: Functional handicap
Time frame: 90 days
Sliding dichotomy/responder analysis: Excellent outcome is defined as modified Rankin Scale (mRS) 0 with baseline National Institutes of Health Stroke Scale (NIHSS), as mRS 0-1 with baseline NIHSS 8-14, as mRS 0-2 with baseline NIHSS ≥15
Proof of concept: Early neurological improvement
Time frame: 22-36 hours
NIHSS=0 or reduction of ≥4 NIHSS points compared with baseline
4 secondary outcomes
Symptomatic intracerebral hemorrhage
Time frame: 24-36 hours
Hemorrhagic transformation
Time frame: 24-36 hours
Short term functional outcome
Time frame: 7 days
Brain infarct size and location
Time frame: 22-36 hours
Results and safety
The study was stopped early (reason given: Lack of funding for researchers). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2020.
- Background: PubMed 26162826Nacu A, Kvistad CE, Logallo N, Naess H, Waje-Andreassen U, Aamodt AH, Solhoff R, Lund C, Tobro H, Ronning OM, Salvesen R, Idicula TT, Thomassen L. A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS). BMC Neurol. 2015 Jul 11;15:110. doi: 10.1186/s12883-015-0359-4.
- Background: PubMed 27980128Nacu A, Kvistad CE, Naess H, Oygarden H, Logallo N, Assmus J, Waje-Andreassen U, Kurz KD, Neckelmann G, Thomassen L. NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): Randomized Controlled Contrast-Enhanced Sonothrombolysis in an Unselected Acute Ischemic Stroke Population. Stroke. 2017 Feb;48(2):335-341. doi: 10.1161/STROKEAHA.116.014644. Epub 2016 Dec 15.
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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.
Lars Thomassen, MD PhD Prof. study director
Dept. Neurology, Haukeland University Hospital, Bergen, Norway
Christopher E Kvistad, MD study chair
Dept. Neurology, Haukeland University Hospital, Bergen, Norway
Haakon Tobro, MD principal investigator
Dept. Neurology, Sykehuset Telemark, Skien
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ultrasound in people with Ischemic Stroke, run by Haukeland University Hospital at 1 site in Norway.
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 3 inclusion and 9 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 15 Apr 2020. 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 Norway. 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.
Are results available for this study?
The study was stopped early (reason given: Lack of funding for researchers). 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?
Clinical: Functional handicap (time frame: 90 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01949961, which also lists 2 linked publications.
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 15 Apr 2020; AzTrials last refreshed its copy on 1 Nov 2026.