The Norwegian Sonothrombolysis in Acute Stroke Study (NOR-SASS)

This study is currently recruiting participants.
Verified September 2013 by Haukeland University Hospital
Sponsor:
Collaborator:
University of Bergen
Information provided by (Responsible Party):
Haukeland University Hospital
ClinicalTrials.gov Identifier:
NCT01949961
First received: September 21, 2013
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

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 endpoint is excellent clinical outcome at 3 months (effect). Secondary endpoints are early clinical improvement (effect) and bleeding complications (safety).


Condition Intervention Phase
Ischemic Stroke
Other: Ultrasound
Other: Sham ultrasound
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomised Trial of Contrast-enhanced Sonothrombolysis in Acute Ischaemic Stroke

Resource links provided by NLM:


Further study details as provided by Haukeland University Hospital:

Primary Outcome Measures:
  • Functional handicap [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    modified Rankin Scale score (mRS) 0-1


Secondary Outcome Measures:
  • Symptomatic intracerebral hemorrhage [ Time Frame: 24-36 hours ] [ Designated as safety issue: Yes ]
    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).

  • Hemorrhagic transformation [ Time Frame: 24-36 hours ] [ Designated as safety issue: Yes ]
    Any hemorrhagic changes (infarct or parenchymal hematoma)

  • Early clinical outcome [ Time Frame: 2 and 24 hours ] [ Designated as safety issue: No ]
    1. NIHSS=0 or reduction of ≥4 NIHSS points compared with baseline
    2. Absolute reduction in NIHSS

  • Short term functional outcome [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 250
Study Start Date: September 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ultrasound
Patients eligible (NOR-SASS 1) and ineligible (NOR-SASS 2) for intravenous thrombolysis all receive intravenous ultrasound contrast (microbubbles). The two groups are separately randomised to 2 MHz transcranial ultrasound treatment for one hour.
Other: Ultrasound
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 VueJet infusion pump. If no infusion pump is available, a bolus of ~2 ml every 5 minutes is given.
Placebo Comparator: Sham ultrasound
Patients eligible (NOR-SASS 1) and ineligible (NOR-SASS 2) 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
Mounting the ultrasound headframe but connecting this to a non-operative channel

Detailed Description:

NOR-SASS aims at testing contrast enhanced sonothrombolysis in all patients with acute ischemic stroke. Patients eligible for thrombolysis are therefore included in NOR-SASS-I sub-study, patients not eligible for thrombolysis are included in NOR-SASS-II 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-I (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-II, randomisation is 1:1 to either CES or no CES.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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;
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01949961

Contacts
Contact: Lars Thomassen, MD PhD Prof. +47 55 97 50 00 ltho@haukeland.no
Contact: Christopher E Kvistad, MD +47 55 97 50 00 echr@helse-bergen.no

Locations
Norway
Dept. of Neurology, Haukeland University Hospital Recruiting
Bergen, Norway, 5021
Sub-Investigator: Christopher E Kvistad, MD         
Sub-Investigator: Aliona Nacu, MD         
Sponsors and Collaborators
Haukeland University Hospital
University of Bergen
Investigators
Study Director: Lars Thomassen, MD PhD Prof. Dept. Neurology, Haukeland University Hospital, Bergen, Norway
Study Chair: Christopher E Kvistad, MD Dept. Neurology, Haukeland University Hospital, Bergen, Norway
Principal Investigator: Aliona Nacu, MD Dept. Neurology, Haukeland University Hospital, Bergen, Norway
  More Information

No publications provided

Responsible Party: Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT01949961     History of Changes
Other Study ID Numbers: REK 2011/2448, 2012-000323-41
Study First Received: September 21, 2013
Last Updated: September 24, 2013
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by Haukeland University Hospital:
intervention
sonothrombolysis
Ultrasound treatment

Additional relevant MeSH terms:
Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia

ClinicalTrials.gov processed this record on April 16, 2014