Clinical trial NCT03702413: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mechanical Thrombectomy
Large Ischemic Core
Keywords: Acute cerebral infarction due to large vessel occlusion
Mechanical thrombectomy
Ischemic stroke
Lead sponsor: Hyogo Medical University
Sponsor class: OTHER
First posted: 2018-10-11
Enrollment: 203
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: modified Rankin Scale ≤3 at 90 days
timeFrame: 90 days
Secondary outcomes:
measure: modified Rankin Scale≤2 at 90 days
timeFrame: 90 days
measure: modified Rankin Scale≤1 at 90 days
timeFrame: 90 days
measure: Distribution of patients across the ordinal modified Rankin scale
timeFrame: 90 days
measure: NIHSS improvement 8 points or more at 48 hours
timeFrame: 48 hours
measure: Symptomatic intracranial hemorrhage within 48 hours
timeFrame: 48 hours
measure: Intracranial hemorrhage within 48 hours
timeFrame: 48 hours
measure: Death
timeFrame: 90 days
measure: Recurrence of cerebral infarction within 90 days
timeFrame: 90 days
measure: Propotion of subjects who required decompressive craniectomy within 7 days
timeFrame: 7 days
Other outcomes:
Locations:
city: Nishinomiya
country: Japan
facility: Hyogo collage of Medicine
state: Hyogo
Study officials:
affiliation: Hyogo Medical University
name: Shinichi Yoshimura, phD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.