Endovascular treatment of patients with extensive cerebral infarction increases the chances of regaining independent walking by 2.4 times - World's first clinical trial proves this

A research group led by Shinichi Yoshimura, Professor Department of Neurosurgery and Tsuyoshi Morimoto, Professor of Clinical Epidemiology Hyogo Medical University (Location: Nishinomiya City, Hyogo Prefecture; President: Koichi Noguchi) conducted the world's first clinical trial at 45 facilities nationwide on patients with extensive cerebral infarction, which had not previously been candidates for endovascular treatment. They found that endovascular treatment increased the rate of recovery to independent walking three months after onset by 2.4 times compared to patients without endovascular treatment.

*The results of this research were reported as a late-breaking clinical trial at the International Stroke Conference 2022 at 2:45 a.m. Japan time on February 10, 2022 (12:45 p.m. Eastern Standard Time on February 9), and were also published in the American medical journal The New England Journal of Medicine.

Research Background.

Endovascular therapy has been proven to improve the neurological prognosis of patients with cerebral infarction caused by occlusion of the main artery, a large artery that supplies blood to the brain, and is widely used at stroke centers nationwide, including our university. However, according to current guidelines, patients recommended for this treatment must be able to start treatment within 6 hours of onset (24 hours if the patient meets the requirements), and must be able to perform daily tasks and activities, in addition to having a localized infarction site on CT or MRI. On the other hand, if the infarction was extensive, endovascular treatment was not recommended because of the high risk of hemorrhagic complications, even if other conditions were met.
In general, the neurological prognosis of patients with extensive cerebral infarction is poor, with only 7.5% of patients able to walk independently after 3 months (Kakita H, Yoshimura S, Uchida K, Sakai N, Yamagami H, Morimoto T. Stroke 2019, presented by our university) and extensive stroke The key question was how to improve the level of independence in patients with extensive cerebral infarction.


The purpose of the study was to determine whether endovascular therapy is effective in improving the quality of life of patients with extensive stroke.

A clinical trial was conducted to determine whether endovascular treatment in addition to standard medical treatment would improve the level of independence after 3 months compared to medical treatment alone in patients with extensive cerebral infarction, for whom endovascular treatment is not recommended under current medical treatment guidelines. (*) The clinical trial was conducted with the cooperation of 45 stroke centers nationwide.

(*) 45 stroke centers nationwide
Seishon Hospital, Hyogo Medical University ・Hironan Hospital, Iwate Prefectural Central Hospital, Disaster Medical Center, Kumamoto Red Cross Hospital, Kobe City Medical Center Chuo Municipal Hospital, Hachinohe Municipal Hospital, Gifu University School of Medicine Affiliated Hospital, Kyushu Medical Center, Niigata Municipal Hospital, Yokohama New City Neurosurgery Hospital, Onishi Neurosurgery Hospital, National Cardiovascular Center, Tenri Yokozu Consultation Center Hospital, Nagareyama Central Hospital, Nagoya Medical Center, Hirosaki University School of Medicine Affiliated Hospital, Yamaguchi University School of Medicine Affiliated Hospital, Araki Neurosurgery Hospital, Kochi Red Cross Hospital, University of Tsukuba Hospital, Tokushima University Hospital, Nippon Medical School, Hakodate Shintoshi Hospital, Nishinomiya Kyoritsu Neurosurgery Hospital, Kawasaki Ko Hospital, Kyoto Second Red Cross Hospital, Saga University School of Medicine Affiliated Hospital, Showa University Hospital Tokyo Metropolitan Tama General Medical Center, Nakamura Memorial Hospital, Seinin-kai Shimizu Hospital, Amagasaki General Medical Center, Osaka Medical Center, Osaka University School of Medicine Affiliated Hospitals, Omagari Kosei Medical Center, Saitama Medical School International Medical Center, Shinko Memorial Hospital, St. Marianna University Toyoko Hospital, Tsuchiura Kyodo Hospital, Tottori University Hospital, Toranomon Hospital Nagasaki Medical Center, Mie University School of Medicine Hospital


Research Methods

A "randomized clinical trial" was conducted to compare a group that receives endovascular treatment in addition to standard medical treatment with a group that receives only medical treatment. 45 facilities nationwide between November 2018 and September 2021 were visited for acute stroke between November 2018 and September 2021, and patients aged 18 years or older who were originally independent in their daily activities were included. If the extent of the stroke was extensive and treatment could be started within 6 hours of onset (24 hours if the time of onset was unknown and MRI indicated that the stroke was not complete), the patient or surrogate consent was obtained and the patient was included in the study.

For patients in the endovascular treatment group, a catheter was inserted through a blood vessel in the thigh to remove a blood clot from a blocked blood vessel in the brain. Patients in both the endovascular and medical treatment-only groups were treated in the same manner for three months after treatment, and their level of independence and adverse events after three months were evaluated by "a physician or physical therapist who was unaware of the assigned treatment.

The planned number of patients was 200, and the follow-up of the last enrolled patients ended on December 20, 2021. The University Department of Neurosurgery served as the research secretariat for the study, with a clinical epidemiology graduate student serving as a member of the event evaluation committee and Reiichi Ishikura, president of the Hyogo Medical University Alumni Association (Midoriki-kai), serving as chair of the imaging evaluation committee.

Ultimately, 203 patients were enrolled, and one patient withdrew consent. 202 patients (100 in the endovascular treatment group and 102 in the medical treatment group; mean age 76 years, 44% female) were followed up to 3 months after onset of disease.


<Source of Research Funds
Mihara Fund for the Promotion of Research on Cerebrovascular Disorders
The Japanese Society for Neuroendovascular Therapy


About the results of the study

Thirty-one out of 100 patients with extensive cerebral infarction who received endovascular treatment and 13 out of 102 patients with extensive cerebral infarction who received only medical treatment recovered to walk independently after 3 months, demonstrating for the first time in the world that endovascular treatment increases the recovery rate by 2.4 times.
This achievement is a breakthrough for patients with extensive cerebral infarction who were not previously eligible for endovascular treatment, as it provides them with a chance to regain their normal daily lives. (See the figure below).

The modified Rankin Scale (mRS) in the figure is used to assess the patient's level of independence, ranging from 0 (no symptoms) to 6 (death). A score of 3 indicates the patient is able to walk without assistance. Endovascular treatment was shown to increase the likelihood of a one-point improvement in the mRS score by 2.4 times and to increase the likelihood of neurological function improvement, such as regaining hand movement or speech, within 48 hours of onset by 3.5 times. Meanwhile, intracranial hemorrhage within 48 hours, regardless of whether symptoms were present or not, occurred in 58% of the endovascular treatment group, a higher rate than in the medical treatment group (31%). However, there was no statistical difference in the incidence of symptomatic intracranial hemorrhage, in which symptoms worsen due to bleeding. Other adverse events also tended to be more frequent in the endovascular treatment group, but no statistical difference was observed.

[Future outlook]
This study demonstrated, for the first time in the world, the effectiveness and safety of endovascular treatment for massive cerebral infarction. As expected, all intracranial hemorrhages were more frequent in the endovascular treatment group. However, the incidence of symptomatic intracranial hemorrhage, in which symptoms worsen due to hemorrhage, was not high and showed no significant difference compared to the medical treatment group. Meanwhile, the recovery rate to independent walking was 2.4 times higher in the endovascular treatment group, demonstrating the effectiveness of the treatment and demonstrating the potential to improve the prognosis of many more patients with massive cerebral infarction. Based on these study results, it is expected that clinicians around the world will perform endovascular treatment on more patients with massive cerebral infarction, leading to improved independence in daily life for many patients worldwide.

[Published Paper Information]

・Medical journals
"New England Journal of Medicine (February 9, 2022). DOI: 10.1056/NEJMoa2118191

・Thesis title
"Endovascular therapy for acute stroke with a large ischemic region"

·author
Yoshimura S, Sakai N, Yamagami H, Uchida K, Beppu M, Toyoda K, Matsumaru Y, MatsumotoY, 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.