The Norwegian Sonothrombolysis in Acute Stroke Study Part 2

Ischemic Stroke Clinical Trial

— NOR-SASS 2  

Official title:

Randomised Trial of Contrast-enhanced Sonothrombolysis in Acute Ischaemic Stroke

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01949961
• Other study ID #: REK 2011/2448
• Secondary ID: 2012-000323-41
• Status: Terminated
• Phase: N/A
• Start date: January 2016
• Est. completion date: December 31, 2019

Study information

• Verified date: August 2018
• Source: Haukeland University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 59
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ischemic 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;

Related Conditions & MeSH terms

• Ischemia
• Ischemic Stroke
• Stroke

Intervention

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 infusion pump.
• Sham ultrasound
Mounting the ultrasound headframe but connecting this to a non-operative channel

Locations

Country	Name	City	State
Norway	Dept. of Neurology, Telemark Hospital	Skien

Sponsors (3)

Lead Sponsor	Collaborator
Haukeland University Hospital	Sykehuset Telemark, University of Bergen

Country where clinical trial is conducted

Norway, 

References & Publications (2)

Nacu A, Kvistad CE, Logallo N, Naess H, Waje-Andreassen U, Aamodt AH, Solhoff R, Lund C, Tobro H, Rønning 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. — View Citation

Nacu A, Kvistad CE, Naess H, Øygarden 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Proof of concept: Early neurological improvement	NIHSS=0 or reduction of =4 NIHSS points compared with baseline	22-36 hours
Secondary	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).	24-36 hours
Secondary	Hemorrhagic transformation	Any hemorrhagic changes (infarct or parenchymal hematoma)	24-36 hours
Secondary	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	7 days
Secondary	Brain infarct size and location	MRI infarct volume and ASPECTS score	22-36 hours