Australasian Nanoparticle-mediated Magnetically Enhanced Diffusion for Ischemic Stroke (AusNanoMED)

Australasian Nanoparticle-mediated Magnetically Enhanced Diffusion for Ischemic Stroke (AusNanoMED)

Rapidly restoring blood flow to the brain in patients with stroke caused by a blocked blood vessel in the brain is the key to reducing disability. Current treatments often leave small blocked arteries that cannot be safely opened with mechanical clot removal devices. Furthermore, stagnant flow limits access of clot-dissolving medication to the clot. This trial tests iron nanoparticles (similar to iron infused to replace low body stores but injected directly into the brain artery upstream of the blockage) combined with an external rotating magnet that draws the nanoparticles towards the clot, overcoming stagnant blood flow. The aim is to bring fresh blood which contains naturally-occurring clot-dissolving substances, and any clot-dissolving medication that may be circulating, to the surface of the clot with the aim of restoring blood flow to the brain. The trial will recruit up to 30 patients. All will receive injection of nanoparticles via an angiogram (small tube inserted into a leg or arm artery and fed up into the brain artery under Xray control). The procedure takes 30min and the degree of success in opening the artery at the end of procedure is the primary outcome, combined with an absence of symptomatic brain bleeding at 24h.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke; Ischemic Stroke
• Intervention / Treatment: Device: Magnetically enhanced diffusion

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bruce Campbell, MBBS FRACP; Phone Number: 61393427000; Email: bruce.campbell@mh.org.au

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2305
      • John Hunter Hospital
      • Contact: Michelle Russell, RN; Phone Number: +61 2 4921 3481; Email: michelle.russell@health.nsw.gov.au
      • Principal Investigator: Ferdi Miteff
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
      • Contact: Alice Ma, MBBS FRACP; Phone Number: 61 2 9926 7111
      • Principal Investigator: Alice Ma, MBBS FRACP
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
      • Contact: Tim Kleinig, MBBS FRACP; Phone Number: 61 8 7074 0000; Email: tim.kleinig@sa.gov.au
      • Principal Investigator: Tim Kleinig, MBBS FRACP
  • Victoria
    • Melbourne, Victoria, Australia, 3168
      • Monash Medical Centre
      • Contact: Ronil V Chandra, MBBS FRANZCR; Phone Number: +61 3 9594 3836
      • Principal Investigator: Ronil V Chandra, MBBS FRANZCR
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
      • Contact: Winston Chong; Phone Number: 61 3 9903 8655
      • Principal Investigator: Winston Chong
    • Melbourne, Victoria, Australia, 3084
      • The Austin Hospital
      • Contact: Hamed Asadi; Phone Number: +61 3 9496 4953
      • Principal Investigator: Hamed Asadi
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
      • Principal Investigator: Bruce Campbell
      • Contact: Bruce Campbell, MBBS FRACP; Phone Number: +61 3 9342 4424

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients presenting with ischemic stroke within 24 hours of the time they were last known to be well
• Patient's age is ≥18 years
• Legal requirements for consent as per local legislative requirements are satisfied.
• Distal medium vessel intracranial arterial occlusion visible on CT-angiography, MR-angiography or catheter digital subtraction angiography (DSA) in the middle cerebral, anterior or posterior cerebral artery. The occlusion may be primary or secondary (ie following initial mechanical thrombectomy of a large vessel occlusion)

Exclusion Criteria:

• Intracranial hemorrhage (ICH) identified by CT or MRI
• Rapidly improving symptoms at the discretion of the investigator
• Pre-stroke mRS score of ≥ 3 (indicating functional dependence)
• Frank hypodensity in >1/3 of the affected arterial territory on non-contrast CT
• CT Perfusion ischemic core volume > 100 ml
• Known automated implantable cardiac defibrillator, pacemaker, cerebral aneurysm clip, cochlear implant, cranial neurostimulator or other device implant that is incompatible with the external magnetic field
• Known allergy or sensitivity to iron
• Known hemochromatosis, or known liver disease such as cirrhosis.
• Known aortic dissection
• Suspected septic embolization
• Contra indication to imaging with contrast agents
• Pregnant or lactating women
• Any terminal illness such that patient would not be expected to survive more than 6 months
• Current participation in another investigational drug or device treatment study
• Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magnetically enhanced diffusion; Intra-arterial iron nanoparticles (4 x 1mg doses delivered every 3 minutes) delivered via microcatheter proximal to site of arterial occlusion(s) with external rotating magnet, total procedure 30min.	Device: Magnetically enhanced diffusion; Iron nanoparticle (intra-arterial) + External magnet workstation; Other Names: PULSE Nanomed System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with substantial reperfusion at final angiography (15 +/- 5min after final nanoparticle injection) without symptomatic intracranial hemorrhage on CT/MRI at 24h	Substantial reperfusion is defined as >50% reperfusion of the target occluded vessel territory at cerebral angiogram 15 (+/- 5) minutes after completion of the final nanoparticle injection. Target occluded vessel territory is defined based on the angiogram immediately prior to nanoparticle injection, as adjudicated by the core laboratory.; Symptomatic intracranial hemorrhage is defined according to the Heidelberg Classification as new intracranial hemorrhage detected by brain imaging within 24h associated with any of the items below in the absence of an alternative explanation for clinical deterioration:≥4 point increase in NIHSS at the time of diagnosis compared to the most recent NIHSS prior to worsening≥2 point increase in one NIHSS categoryLeading to intubation/hemicraniectomy/external ventricular drain placement or other major medical/surgical intervention	24 hours +/- 6 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants with >90% reperfusion of the target occluded vessel territory at cerebral angiogram 15 (+/- 5) minutes after completion of the final nanoparticle injection	- Near-complete reperfusion is defined as >90% reperfusion of the target occluded vessel territory at cerebral angiogram 15 (+/- 5) minutes after completion of the final nanoparticle injection. Target occluded vessel territory is defined based on the angiogram immediately prior to nanoparticle injection, as adjudicated by the core laboratory	15 minutes +/- 5 minutes after completion of the final nanoparticle injection
Symptomatic intracranial hemorrhage	- Symptomatic intracranial hemorrhage is defined according to the Heidelberg Classification as new intracranial hemorrhage detected by brain imaging within 24h associated with any of the items below in the absence of an alternative explanation for clinical deterioration: ≥4 point increase in NIHSS at the time of diagnosis compared to the most recent NIHSS prior to worsening; ≥2 point increase in one NIHSS category; Leading to intubation/hemicraniectomy/external ventricular drain placement or other major medical/surgical intervention	24 hours +/- 6 hours
Procedural arterial perforation	Procedural arterial perforation that results in visible extravasation of contrast into the subarachnoid space	24 hours +/- 6 hours
Death due to any cause	Death due to any cause within 90 days	90 days +/- 7 days
modified Rankin Scale (mRS) at 3 months	Modified Rankin Scale ranges from 0 (no symptoms of stroke) to 6 (death), high scores indicate worse outcome. Outcome is descriptive and ordinal analysis compared to historical control (adjusted for baseline NIHSS and age).	90 days +/- 7 days
modified Rankin Scale (mRS) 0-1 or no change from baseline at 3 months	Modified Rankin Scale ranges from 0 (no symptoms of stroke) to 6 (death), high scores indicate worse outcome. Outcome is descriptive and compared to historical control (adjusted for baseline NIHSS and age).	90 days +/- 7 days
modified Rankin Scale (mRS) 0-2 or no change from baseline at 3 months	Modified Rankin Scale ranges from 0 (no symptoms of stroke) to 6 (death), high scores indicate worse outcome. Outcome is descriptive and compared to historical control (adjusted for baseline NIHSS and age).	90 days +/- 7 days
Early neurological improvement	8 point reduction in National Institutes of Health Stroke Scale (NIHSS) score or reaching 0-1 at 3 days. NIHSS ranges from 0-42 with higher scores representing more severe stroke. Outcome is descriptive and compared to historical control (adjusted for baseline NIHSS and age).	3 days +/- 1 day or discharge if earlier
Reperfusion at 24 hours	Resolution of perfusion lesion (<5mL region of brain with hypoperfusion defined as Tmax delay >6 sec) at 24 hours	24 hours +/- 6 hours
Recanalization at 24 hours	Resolution of arterial occlusion at 24 hours assessed using the arterial occlusive lesion (AOL) scale 3. AOL ranges from 0 (no recanalization) to 3 (complete recanalization).	24 hours +/- 6 hours

Collaborators and Investigators

• Sponsor: University of Melbourne
• Collaborators: Monash University; Euphrates Vascular, Inc.
• Investigators: Principal Investigator: Bruce CV Campbell, MBBS FRACP, University of Melbourne; Principal Investigator: Ronil V Chandra, MBBS FRANZCR, Monash University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: July 7, 2024
• First Posted (Actual): July 11, 2024

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 7, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: thrombolysis; nanoparticle; digital subtraction angiography; thrombolytic; endovascular thrombectomy; magnetically enhanced diffusion
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: MBC2402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes