Randomized Controlled Trial of Endovascular Therapy for Acute Large Vessel Occlusion With Large Ischemic Core

• ClinicalTrials.gov Identifier: NCT03702413
• Recruitment Status: Completed
• First Posted: October 11, 2018
• Last Update Posted: July 12, 2022
• Sponsor: Hyogo Medical University
• Information provided by (Responsible Party): Shinichi Yoshimura, Hyogo Medical University

Tracking Information

• First Submitted Date: October 4, 2018
• First Posted Date: October 11, 2018
• Last Update Posted Date: July 12, 2022
• Actual Study Start Date: November 30, 2018
• Actual Primary Completion Date: December 21, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 8, 2018)

modified Rankin Scale ≤3 at 90 days [ Time Frame: 90 days ]

The primary endpoint of the trial is the modified Rankin Scale (mRS) ≤3 at 90 days post-stroke.The scale runs from 0-6 with 0 being perfect health without symptoms to 6 being death. 0: No symptoms.

1. No significant disability. Able to carry out all usual activities, despite some symptoms.
2. Slight disability. Able to look after own a符airs without assistance, but unable to carry out all previous activities.
3. Moderate disability. Requires some help, but able to walk unassisted.
4. Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
5. Severe disability. Requires constant nursing care and a悦ention, bedridden, incontinent.
6. Dead.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 8, 2018)

• modified Rankin Scale≤2 at 90 days [ Time Frame: 90 days ]
  Functional independence as difined by modified Rankin ScalemRS≤2 at 90 days
• modified Rankin Scale≤1 at 90 days [ Time Frame: 90 days ]
  Excellent outcome as difined by modified Rankin Scale≤1 at 90 days
• Distribution of patients across the ordinal modified Rankin scale [ Time Frame: 90 days ]
  The difference in linear trends in ordinal mRS outcomes between treatment groups (mRS shift analysis)
• NIHSS improvement 8 points or more at 48 hours [ Time Frame: 48 hours ]
  Early improvement of neulogical findings
• Symptomatic intracranial hemorrhage within 48 hours [ Time Frame: 48 hours ]
  Defined as NIHSS worsening of 4 or more points associated with ICH within 48 hours of randomization
• Intracranial hemorrhage within 48 hours [ Time Frame: 48 hours ]
  The incidence of hemorrhage
• Death [ Time Frame: 90 days ]
  Death due to any cause at 90 days
• Recurrence of cerebral infarction within 90 days [ Time Frame: 90 days ]
  Recurrence of cerebral infarction
• Propotion of subjects who required decompressive craniectomy within 7 days [ Time Frame: 7 days ]
  Propotion of subjects who had space-occupying infarction (malignant brain edema) and requred decompressive craniectomy within 7 days

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Randomized Controlled Trial of Endovascular Therapy for Acute Large Vessel Occlusion With Large Ischemic Core
• Official Title: Randomized Controlled Trial of Endovascular Therapy for Acute Large Vessel Occlusion With Large Ischemic Core (RESCUE Japan LIMIT)

Brief Summary

RESCUE-Japan LIMIT(Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan Large IscheMIc core Trial) is a prospective, open label, blinded endpoint (PROBE), Japanese, two-arm, randomized, controlled, post-market study to compare the effectiveness of endovascular treatment as compared to best medical treatment alone in the acute ischemic stroke patients with an low ASPECTS (CT-ASPECTS 3-5 or DWI-ASPECTS 3-5).

The purpose of this study is to investigate the efficacy of endovascular treatment for acute large vessel occlusion with large ischemic core (CT-ASPECT score 3-5 or DWI-ASPECT score 3-5).

Detailed Description

In the American Heart Association guideline 2018, endovascular therapy (EVT) has been strongly recommended as class of recommendation (COR) I for for the patients with acute cerebral large vessel occlusion (LVO), the Alberta Stroke Program Early CT Score (ASPECTS) 6 or more. The efficacy of EVT for the patients with low ASPECTS remains unclear.

This study is a prospective, open label, blinded endpoint (PROBE), Japanese, two-arm, randomized, controlled, post-market study to compare the effectiveness of endovascular treatment as compared to best medical treatment alone for acute large vessel occlusion patients with large ischemic core (ASPECTS 3-5 or DWI-ASPECTS 3-5).

Up to 200 subjects will be enrolled in the study and randomized for the Intention to treat analysis set. The randomization will be stratified by treatment institutes, patient's age (less than 75 years old or not), time from symptom onset (0-2 hours or more than 2 hours), and stroke severity (NIHSS 21 or more/less than 21), and administration of rt-PA.

Subjects who meet the inclusion criteria will be randomized in a 1:1 ratio to one of the following two treatment arms: Arm 1: best medical treatment Arm 2: best medical treatment plus endovascular treatment

Primary outcome of this study is to investigate efficacy of endivascular treatment in acute stroke patients with large ischemic core (ASPECTS 3-5 or DWI-ASPECTs 3-5) as compared to best medical treatment alone.

Approximately 40 sites in Japan Patients presenting with acute ischemic stroke (AIS) based on focal occlusion in the M1 segment of the middle cerebral artery (MCA), and/or the intracranial segment of the distal internal carotid artery (ICA), determined by Magnetic Resonance Angiography (MRA) or Computed Tomographic Angiography (CTA), and who meet all eligibility criteria will be considered for study enrollment.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Mechanical Thrombectomy
• Large Ischemic Core

Intervention

Procedure: Endovascular treatment

Acute thrombectomy

Study Arms

• No Intervention: Best medical treatment
  Best medical treatment
• Experimental: Endovascular treatment
  Best medical treatment plus endovascular treatment
  Intervention: Procedure: Endovascular treatment

Publications *

• Uchida K, Shindo S, Yoshimura S, Toyoda K, Sakai N, Yamagami H, Matsumaru Y, Matsumoto Y, Kimura K, Ishikura R, Yoshida A, Inoue M, Beppu M, Sakakibara F, Shirakawa M, Morimoto T; RESCUE-Japan LIMIT Investigators. Association Between Alberta Stroke Program Early Computed Tomography Score and Efficacy and Safety Outcomes With Endovascular Therapy in Patients With Stroke From Large-Vessel Occlusion: A Secondary Analysis of the Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Large Ischemic Core Trial (RESCUE-Japan LIMIT). JAMA Neurol. 2022 Dec 1;79(12):1260-1266. doi: 10.1001/jamaneurol.2022.3285. Erratum In: JAMA Neurol. 2022 Dec 12;:
• Yoshimura S, Sakai N, Yamagami H, Uchida K, Beppu M, Toyoda K, Matsumaru Y, Matsumoto Y, Kimura K, Takeuchi M, Yazawa Y, Kimura N, Shigeta K, Imamura H, Suzuki I, Enomoto Y, Tokunaga S, Morita K, Sakakibara F, Kinjo N, Saito T, Ishikura R, Inoue M, Morimoto T. Endovascular Therapy for Acute Stroke with a Large Ischemic Region. N Engl J Med. 2022 Apr 7;386(14):1303-1313. doi: 10.1056/NEJMoa2118191. Epub 2022 Feb 9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 9, 2021): 203
• Original Estimated Enrollment (submitted: October 8, 2018): 200
• Actual Study Completion Date: March 30, 2022
• Actual Primary Completion Date: December 21, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Acute cerebral infarction
2. Age ≥ 18
3. NIHSS ≥ 6
4. Prestroke Modified Rankin Score 0-1
5. ICA or M1 Occlusion on CT angiography or MR angiography
6. ASPECTS 3-5 or DWI-ASPECTS 3-5
7. Randamization can be finished within 6 hours from last known well time, or 6 to 24 hours from last well known well time without positive lesion on MRI-FLAIR image.
8. Endovascular treatment can be initiatedwithin 60 minutes from randomization
9. Patient or Legally Authorized Representative has signed the Informed Consent form

Exclusion Criteria:

1. Significant mass effect with midline shift
2. Known allergy to contrast agents
3. Evidence of acute intracranial hemorrhage
4. Female who is pregnant or suspicision of pregnant
5. Clinical evidence of chronic occlusion
6. High risk of hemorrhage (platelet < 40,000 /µL, APTT > 50 second or PT-INR > 3.0)
7. Participating in any other therapeutic investigational trial
8. Subjects who, in the judgment of the investigator, are likely to be non-compliant or uncooperative during the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT03702413
• Other Study ID Numbers: R000038184
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shinichi Yoshimura, Hyogo Medical University
• Original Responsible Party: Same as current
• Current Study Sponsor: Hyogo Medical University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Shinichi Yoshimura, phD; Hyogo Medical University

• PRS Account: Hyogo Medical University
• Verification Date: July 2022