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

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Mechanical Thrombectomy; Large Ischemic Core	Procedure: Endovascular treatment	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 203 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Trial of Endovascular Therapy for Acute Large Vessel Occlusion With Large Ischemic Core (RESCUE Japan LIMIT)
• Actual Study Start Date: November 30, 2018
• Actual Primary Completion Date: December 21, 2021
• Actual Study Completion Date: March 30, 2022

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Best medical treatment; Best medical treatment
Experimental: Endovascular treatment; Best medical treatment plus endovascular treatment	Procedure: Endovascular treatment; Acute thrombectomy

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. modified Rankin Scale≤2 at 90 days [ Time Frame: 90 days ]
   Functional independence as difined by modified Rankin ScalemRS≤2 at 90 days
2. modified Rankin Scale≤1 at 90 days [ Time Frame: 90 days ]
   Excellent outcome as difined by modified Rankin Scale≤1 at 90 days
3. 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)
4. NIHSS improvement 8 points or more at 48 hours [ Time Frame: 48 hours ]
   Early improvement of neulogical findings
5. 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
6. Intracranial hemorrhage within 48 hours [ Time Frame: 48 hours ]
   The incidence of hemorrhage
7. Death [ Time Frame: 90 days ]
   Death due to any cause at 90 days
8. Recurrence of cerebral infarction within 90 days [ Time Frame: 90 days ]
   Recurrence of cerebral infarction
9. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Japan

Hyogo collage of Medicine

Nishinomiya, Hyogo, Japan, 665-8501

Sponsors and Collaborators

Hyogo Medical University

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Shinichi Yoshimura, Department of Neurosurgery, Hyogo Medical University
• ClinicalTrials.gov Identifier: NCT03702413
• Other Study ID Numbers: R000038184
• First Posted: October 11, 2018
• Last Update Posted: July 12, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Shinichi Yoshimura, Hyogo Medical University:

Acute cerebral infarction due to large vessel occlusion; Mechanical thrombectomy; Ischemic stroke

Additional relevant MeSH terms:

Ischemia; Pathologic Processes