Ischemic Stroke, Stroke
Conditions
Keywords
thrombolysis, thrombolytic, endovascular thrombectomy, nanoparticle, magnetically enhanced diffusion, digital subtraction angiography
Brief summary
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.
Interventions
DEVICEMagnetically enhanced diffusion
Iron nanoparticle (intra-arterial) + External magnet workstation
Sponsors
Monash University
Euphrates Vascular, Inc.
University of Melbourne
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Primary outcome assessed by blinded imaging core laboratory. Day 90 modified Rankin scale assessed by central blinded clinician.
Intervention model description
Bayesian optimal phase 2 trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with substantial reperfusion at final angiography (15 +/- 5min after final nanoparticle injection) without symptomatic intracranial hemorrhage on CT/MRI at 24h | 24 hours +/- 6 hours | * 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 category * Leading to intubation/hemicraniectomy/external ventricular drain placement or other major medical/surgical intervention |
Other
| Measure | Time frame | Description |
|---|---|---|
| Early neurological improvement | 3 days +/- 1 day or discharge if earlier | 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). |
| Reperfusion at 24 hours | 24 hours +/- 6 hours | Resolution of perfusion lesion (\<5mL region of brain with hypoperfusion defined as Tmax delay \>6 sec) at 24 hours |
| Recanalization at 24 hours | 24 hours +/- 6 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). |
| 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 | 15 minutes +/- 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 |
| modified Rankin Scale (mRS) 0-2 or no change from baseline at 3 months | 90 days +/- 7 days | 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). |
| Procedural arterial perforation | 24 hours +/- 6 hours | Procedural arterial perforation that results in visible extravasation of contrast into the subarachnoid space |
| Death due to any cause | 90 days +/- 7 days | Death due to any cause within 90 days |
| modified Rankin Scale (mRS) at 3 months | 90 days +/- 7 days | 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). |
| modified Rankin Scale (mRS) 0-1 or no change from baseline at 3 months | 90 days +/- 7 days | 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). |
| Symptomatic intracranial hemorrhage | 24 hours +/- 6 hours | \- 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 |
Countries
Australia
Contacts
Primary ContactBruce Campbell, MBBS FRACP
Outcome results
None listed