Remote ischemic conditioning for acute ischemic stroke part 2: Study protocol for a randomized controlled trial

 And all this earlier research was not enough?

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  Leg wraps raise hopes of saved lives after strokes May 2013 

  
  

  Leg compressions may enhance stroke recovery August 2012

The latest here:

Remote ischemic conditioning for acute ischemic stroke part 2: Study protocol for a randomized controlled trial

Kentaro Ishizuka^1*, Takao Hoshino¹, Sono Toi¹, Takafumi Mizuno¹, Megumi Hosoya¹, Moeko Saito¹, Yasuto Sato², Yoshiki Yagita³, Kenichi Todo⁴, Manabu Sakaguchi⁵, Takashi Ohashi⁶, Kenji Maruyama⁷, Shuji Hino⁸, Yutaka Honma⁹, Ryosuke Doijiri¹⁰, Hiroshi Yamagami¹¹, Yasuyuki Iguchi¹², Teruyuki Hirano¹³, Kazumi Kimura¹⁴, Takanari Kitazono¹⁵ and Kazuo Kitagawa^1*

• ¹Department of Neurology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
• ²Department of Public Health, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
• ³Department of Stroke Medicine, Kawasaki Medical School, Okayama, Japan
• ⁴Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
• ⁵Department of Neurology, Osaka General Medical Center, Osaka, Japan
• ⁶Department of Neurology, Tokyo Women's Medical University Yachiyo Medical Center, Chiba, Japan
• ⁷Department of Neurology, Toda Chuo General Hospital, Saitama, Japan
• ⁸Department of Neurology, Saitama Red Cross Hospital, Saitama, Japan
• ⁹Department of Neurology, Showa General Hospital, Tokyo, Japan
• ¹⁰Department of Neurology, Iwate Prefectural Central Hospital, Iwate, Japan
• ¹¹Department of Stroke Neurology, National Hospital Organization, Osaka National Hospital, Osaka, Japan
• ¹²Department of Neurology, The Jikei University School of Medicine, Tokyo, Japan
• ¹³Department of Stroke and Cerebrovascular Medicine, Kyorin University, Tokyo, Japan
• ¹⁴Department of Neurology, Nippon Medical School, Tokyo, Japan
• ¹⁵Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Background: Remote ischemic conditioning (RIC) refers to the application of repeated short periods of ischemia intended to protect remote areas against tissue damage during and after prolonged ischemia.

Aim: We aim to evaluate the efficacy of RIC, determined by the modified Rankin Scale (mRS) score at 90 days after stroke onset.

Design and methods: This study is an investigator-initiated, multicenter, prospective, randomized, open-label, parallel-group clinical trial. The sample size is 400, comprising 200 patients who will receive RIC and 200 controls. The patients will be divided into three groups according to their National Institutes of Health Stroke Scale score at enrollment: 5–9, mild; 10–14, moderate; 15–20, severe. The RIC protocol will be comprised of four cycles, each consisting of 5 min of blood pressure cuff inflation (at 200 mmHg or 50 mmHg above the systolic blood pressure) followed by 5 min of reperfusion, with the cuff placed on the thigh on the unaffected side. The control group will only undergo blood pressure measurements before and after the intervention period. This trial is registered with the UMIN Clinical Trial Registry (https://www.umin.ac.jp/: UMIN000046225).

Study outcome: The primary outcome will be a good functional outcome as determined by the mRS score at 90 days after stroke onset, with a target mRS score of 0–1 in the mild group, 0–2 in the moderate group, and 0–3 in the severe group.

Discussion: This trial may help determine whether RIC should be recommended as a routine clinical strategy for patients with ischemic stroke.

Introduction

In recent years, hyperacute reperfusion treatment has progressed remarkably due to the establishment of recombinant tissue-type plasminogen activator (rt-PA) and endovascular treatment (EVT) (1, 2). Although Japan is proceeding with a plan to accelerate the development of an efficient care system for stroke patients (forming new stroke centers and stroke care units), only 6–8% of patients can receive hyperacute reperfusion therapy (3). In Japan, edaravone has been used as an effective method to reduce ischemic insults. However, it is not widely used internationally; it has yet to demonstrate sufficient efficacy (4).

Remote ischemic conditioning (RIC) is a therapeutic strategy in which several cycles of brief focal ischemia, followed by reperfusion in the arms or legs, confer protection against the more severe detrimental effects of ischemia in target organs (5–8). Although the underlying mechanisms are not fully understood, current evidence indicates that RIC reduces inflammation, oxidative stress, and cerebral edema, mediated by humoral, immunoregulatory, and neurotrophic factors (9). Although the clinical application of RIC in patients with acute ischemic stroke has been attempted, its efficacy has not yet been validated (10–12). Moreover, no clinical trials have been conducted on acute ischemic strokes in Japan.

One reason for the inability to confirm the efficacy of RIC in previous studies may be the use of a unified definition of a good outcome as assessed by the modified Rankin Scale (mRS), regardless of the neurological severity of the enrolled patients upon admission. Another reason may be the lack of an established RIC protocol. Therefore, this study aims to evaluate the efficacy of an RIC protocol based on recent literature, determined by the mRS score at 90 days after stroke onset, with a good outcome defined according to the severity at enrollment.