The Norwegian Sonothrombolysis in Acute Stroke Study Part 2

NCT01949961 | Terminated DMC

• 2 other identifiers: REK 2011/24482012-000323-41
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief 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. 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).

Conditions

Ischemic Stroke

Keywords

intervention; sonothrombolysis; Ultrasound treatment

Outcome Measures

Primary Outcomes (2)

• 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

  90 days

• Proof of concept: Early neurological improvement

  NIHSS=0 or reduction of ≥4 NIHSS points compared with baseline

  22-36 hours

Secondary Outcomes (4)

• Symptomatic intracerebral hemorrhage

  24-36 hours

• Hemorrhagic transformation

  24-36 hours

• Short term functional outcome

  7 days

• Brain infarct size and location

  22-36 hours

Study Arms (2)

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.

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.

Other: Sham ultrasound

Interventions

Ultrasound OTHER

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.

Ultrasound

Sham ultrasound OTHER

Mounting the ultrasound headframe but connecting this to a non-operative channel

Sham ultrasound

Eligibility Criteria

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

You may qualify if:

• Ischemic stroke in the anterior circulation
• Treatment within 4.5 hours after stroke onset
• Informed consent

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Haukeland University Hospital: lead
• University of Bergen: collaborator
• Sykehuset Telemark: collaborator

Study Sites (1)

Dept. of Neurology, Telemark Hospital

Skien, 3710, Norway

Location

Related Publications (2)

• 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.

  PMID: 26162826 BACKGROUND

• Nacu 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.

  PMID: 27980128 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke

Interventions

High-Energy Shock Waves

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Lars Thomassen, MD PhD Prof.

  Dept. Neurology, Haukeland University Hospital, Bergen, Norway

  STUDY DIRECTOR

• Christopher E Kvistad, MD

  Dept. Neurology, Haukeland University Hospital, Bergen, Norway

  STUDY CHAIR

• Haakon Tobro, MD

  Dept. Neurology, Sykehuset Telemark, Skien

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: PROBE: Prospective randomized open-label blinded-endpoint

Study Record Dates

• First Submitted: September 21, 2013
• First Posted: September 25, 2013
• Study Start: January 1, 2016
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: April 15, 2020

Record last verified: 2018-08

Locations

NO (1)