Magnetically Enhanced Diffusion for Acute Ischaemic Stroke (MEDIS) Trial (MEDIS)

A Prospective International Multicentre Randomised Controlled Single Blind Clinical Investigation of Magnetically Enhanced Diffusion for Acute Ischaemic Stroke (MEDIS)

The objective of the MEDIS study is to determine if subjects experiencing an Acute Ischaemic Stroke due to large vessel occlusion, treated with IV tPA combined with the MED procedure have a greater likelihood of recanalisation 30-90 minutes after the completion of tPA infusion than subjects treated with IV tPA (plus sham device). Safety of the MED System Procedure will be evaluated by the incidence of symptomatic PH-2 haemorrhagic transformation within 24 hours following the procedure. Lastly, a health economics study will be conducted to estimate health care costs for each treatment.

Study Overview

• Status: Suspended
• Conditions: Cerebrovascular Disorders; Neurologic Disorder; Infarction, Middle Cerebral Artery; Stroke, Ischemic; Stroke, Acute; Intracranial Embolism and Thrombosis; Strokes Thrombotic
• Intervention / Treatment: Device: Magnetically Enhanced Diffusion (MED); Device: MED Workstation Magnet Sham Control

Detailed Description

The study is a global, multicentre prospective, randomised, single blind, blinded endpoint study comparing rates of early recanalisation (defined by mAOL) in Acute Ischaemic Stroke (AIS) subjects with visible occlusion who are treated with either IV tPA plus sham device or IV tPA in combination with the MED System procedure.

The study population will be randomised 1:1 into two arms:

• A Sham Control Group (SCG) and an
• Experimental Treatment Group (ETG).

The ETG will receive IV tPA and the complete MED System procedure consisting of MED MicroBeads and the MED Workstation magnet procedure. The SCG will not receive MED MicroBeads while the MED Workstation will be activated as a Sham control. Subjects will be blinded to treatment arm. Stratification will be performed based upon baseline age and location of the occlusion (Middle Cerebral Artery segments M1, M2, or Carotid Terminus).

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Chester, United Kingdom, CH2 1UL
    • Countess Of Chester Hospital NHS Foundation Trust
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • Queen Elizabeth University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 and <85
2. Clinical signs consistent with acute ischaemic stroke
3. Prestroke functional independence (prestroke Modified Rankin Score ≤2)
4. NIHSS 4-25 at the time of randomisation
5. Initiation of IV tPA (alteplase or tissue Plasminogen Activator) within the locally approved time window from stroke symptom onset (onset time is defined as the last time when the subject was witnessed to be at baseline).
6. Arterial Occlusive Lesion (mAOL ≤1) in the M1 or M2 segments of the MCA (Middle Cerebral Artery) or carotid terminus confirmed by CT angiography.
7. Subject is able to start the MED procedure within 15 +10 minutes) from the t-PA IV infusion, and complete 60+15 minutes of MED procedure treatment.
8. Subject or subject's legally authorised representative has signed and dated an Informed Consent Form according to country regulations, ethics committee, and/or Institutional Review Board requirements.
9. It is the enrolling Investigator's or designee's opinion based upon the knowledge of the Subject's condition as well as the features of the MED device, that the Subject is an appropriate candidate for stroke management utilizing MED.

Exclusion Criteria:

1. The subject is likely to receive intra-arterial (IA) intervention.
2. Standard exclusions for thrombolysis according to the approved label and local institutional protocols.
3. Female who is pregnant or lactating or has a positive pregnancy test at time of admission.
4. Rapid neurological improvement prior to study randomisation suggesting resolution of the occlusion.
5. Known hyper-sensitivity to radiographic contrast agents.
6. Known hyper-sensitivity to iron-based agents or polyethylene glycol.
7. Known or suspected symptomatic haemosiderosis or haemochromatosis.
8. Has a previous or existing cardiovascular condition resulting in history of heart block, tachybrady syndrome, symptomatic postural hypotension requiring medical intervention.
9. Current participation or participation in the last 4 weeks in another investigational drug or device treatment study.
10. Life expectancy of less than 90 days due to other medical condition.
11. Subject with a pre-existing neurological or psychiatric disease that would confound the neurological and functional evaluations.
12. Subject has contraindications to Magnetic Resonance Imaging (MR; examples include, but are not limited to, an implantable cardioverter defibrillator, pacemaker, clipped or coiled aneurysm, neurostimulator).
13. Subject has recently (within 30 days) received iron replacement therapy or iron based MR contrast.
14. Subject has known or suspected liver disease, including hepatitis and/or cirrhosis.

Imaging Exclusion Criteria:

1. Computed tomography (CT) or MRI evidence of haemorrhage on presentation.
2. Exclusion: Large core of ischemia defined as NCCT ASPECTS 4 or less.
3. CT or MRI evidence of mass effect or intra-cranial tumour (except small meningioma).
4. CTA or MRA (CT or MR Angiography) evidence of carotid dissection or complete cervical carotid occlusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Magnetically Enhanced Diffusion (MED); The Experimental Treatment will receive the complete MED System Procedure consisting of MED MicroBeads and the MED Workstation magnet procedure for 60 minutes in addition to IV tissue plasminogen activator (tPA or Alteplase).	Device: Magnetically Enhanced Diffusion (MED); Treatment of Acute Ischemic Stroke with IV tPA and the adjunctive Magnetically Enhanced Diffusion (MED) System Procedure.; Other Names: MED Workstation; MED MicroBeads
SHAM_COMPARATOR: MED Workstation Magnet Sham Control; The MED Workstation Magnet Sham Comparator will not receive MED MicroBeads while the MED Workstation Magnet will be activated as a Sham control for 60 minutes in addition to IV tissue plasminogen activator (tPA or Alteplase).	Device: MED Workstation Magnet Sham Control; Treatment of Acute Ischemic Stroke with IV tPA and Sham use of the MED Workstation only, without the injection of MED MicroBeads.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Performance: Early Recanalisation 60 +/- 30 minutes after IV tPA completion	Early recanalisation (Arterial Occlusive Lesion [mAOL] score) assessed from a blinded evaluation of Computed Tomographic Angiography (CTA) imaging of the primary lesion 60+/- 30 minutes after completion of tPA infusion. An ordinal shift analysis of the mAOL score distribution between the Sham Control and MED System Procedure arms will be conducted.	60 +/- 30 minutes after completion of IV tPA administration.
Primary Safety: Incidence of Symptomatic Type 2 Parenchymal (PH-2) Haemorrhagic Transformation	Incidence of symptomatic PH-2 haemorrhagic transformation at 24 ± 6 hours post randomisation as determined by NCCT combined with a neurological deterioration that includes an increase of 4 points or more on the NIHSS from baseline or the lowest NIHSS value between baseline and 24 hours, or leading to death.	24 ± 6 Hours after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Clinical Performance Endpoint: Neurological outcome mRS at 90 days	Neurological outcome as defined by modified Rankin score (mRS) at 90 days.	90 days after randomisation
Secondary Technical Clinical Performance Endpoint: Cerebral Infarct volume at 24 Hours	Volume of cerebral infarction as measured by Non-Contrast Computed Tomography (NCCT) at 24 ± 6 hours post randomisation.	24 ± 6 hours after randomisation

Collaborators and Investigators

• Sponsor: Pulse Therapeutics
• Investigators: Principal Investigator: Keith W Muir, MBChB, University of Glasgow

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 22, 2017
• Primary Completion (ANTICIPATED): December 31, 2019
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: March 27, 2017
• First Posted (ACTUAL): April 4, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 28, 2019
• Last Update Submitted That Met QC Criteria: January 24, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Stroke; Vascular Diseases; Ischemic; Cerebrovascular Disorders; Thrombolysis; Tissue Plasminogen Activator; Plasminogen; Fibrinolytic Agents
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Thromboembolism; Cerebral Infarction; Stroke; Disease; Ischemic Stroke; Embolism; Ischemia; Nervous System Diseases; Thrombosis; Infarction, Middle Cerebral Artery; Cerebrovascular Disorders; Embolism and Thrombosis; Thrombotic Stroke; Intracranial Embolism; Intracranial Embolism and Thrombosis
• Other Study ID Numbers: MEDIS-INT16-002

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