Albumin for patients with acute large-vessel occlusive stroke undergoing endovascular therapy (ARISE): the protocol of a randomized double-blind trial

Your competent? doctor knows all about this, right? Oh no, you DON'T have a functioning stroke doctor or hospital, do you? RUN AWAY!

With nothing being done, YOUR BOARD OF DIRECTORS IS COMPLETELY FUCKING INCOMPETENT!

albumin (4 posts to October 2011)

Albumin to globulin ratio (1 post to April 2022)

fibrinogen-to-albumin ratio (1 post to March 2022)

hemoglobin-albumin cluster (1 post to July 2018)

lactate-to-albumin ratio (1 post to July 2023)

 Albumin for patients with acute large-vessel occlusive stroke undergoing endovascular therapy (ARISE): the protocol of a randomized double-blind trial

Yuanyuan Liu^1†, Xiao Dong^1†, Xuehong Chu¹, Zhengfei Ma², Tingyu Yi^3,4, Changming Wen⁵, Yifeng Liu⁵, Jun Sun⁵, Jing Xu⁶, Wenbo Li⁷, Lei Yang⁸, Benxiao Wang⁹, Lei Shi¹⁰, Jianqiao Li¹¹, Xiaoman Zhang¹², Chaoqun Li¹³, Wenhuo Chen¹⁴, Chuanhui Li¹, Di Wu¹⁵, Chengbei Hou¹⁶, Chen Zhou¹⁷, Ming Li^15,17, Yi Xu¹, Chuanjie Wu^1* and Xunming Ji^1,17*

¹Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China

²Department of Neurology, Suzhou Municipal Hospital, Suzhou, Anhui, China

³Department of Neuro-intervention, Zhangzhou Municipal Hospital, Zhangzhou, Fujian, China

⁴Department of Neuro-intervention, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China

⁵Department of Neurology, Nanyang Central Hospital, Nanyang, Henan, China

⁶Department of Neurology, Maanshan People's Hospital, Maanshan, Anhui, China

⁷Department of Neurology, Luoyang Central Hospital Affiliated To Zhengzhou University, Luoyang, Henan, China

⁸Department of Neurology, Liaocheng Third People's Hospital, Liaocheng, Shandong, China

⁹Department of Neurology, WanBei Coal-Electricity Group General Hospital, Suzhou, Anhui, China

¹⁰Department of Neurology, Si County People's Hospital, Anhui, China

¹¹Department of Neurology, Sui Xi County Hospital, Huaibei, Anhui, China

¹²Department of Neurology, The First People’s Hospital of Zhengzhou, Zhengzhou, Henan, China

¹³Department of Neurology, Xihua County People's Hospital, Zhoukou, Henan, China

¹⁴Department of Cerebrovascular Disease, Fujian Medical University Union Hospital, Fujian, China

¹⁵China-America Institute of Neuroscience and Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China

¹⁶Center for Evidence Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China

¹⁷Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China

Edited by
Patricia Martínez Sánchez, Torrecárdenas University Hospital, Spain

Reviewed by
Shenqiang Yan, Zhejiang University, China
Sharon Yeatts, Medical University of South Carolina, United States
Yu Xie, Wuhan University, China

*Correspondence
Chuanjie Wu, wuchuanjie@ccmu.edu.cn; Xunming Ji, jixm@ccmu.edu.cn

^†These authors have contributed equally to this work

Received 03 February 2025
Accepted 24 June 2025
Published 18 July 2025

Citation
Liu Y, Dong X, Chu X, Ma Z, Yi T, Wen C, Liu Y, Sun J, Xu J, Li W, Yang L, Wang B, Shi L, Li J, Zhang X, Li C, Chen W, Li C, Wu D, Hou C, Zhou C, Li M, Xu Y, Wu C and Ji X (2025) Albumin for patients with acute large-vessel occlusive stroke undergoing endovascular therapy (ARISE): the protocol of a randomized double-blind trial. Front. Neurol. 16:1570184. doi: 10.3389/fneur.2025.1570184

Background: Albumin is a multifunctional plasma protein that is mainly synthesized in the liver and may play a neuroprotective role in treating acute ischemic stroke (AIS). The efficacy of albumin in patients with AIS receiving reperfusion therapy remains unknown.

Methods: ARISE is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study. We will recruit 134 patients aged 18–80 years with AIS due to large-vessel occlusion in the anterior circulation, within 24 h of symptom onset, with an Alberta Stroke Program Early CT Score of 3–10 points and an infarct core volume of ≤100 mL at baseline. Eligible patients will be randomly assigned, on a 1:1 ratio, to undergo endovascular therapy (EVT) and receive albumin therapy (0.5 g/kg; intravenous injection) once daily for 4 days or to undergo EVT and receive placebo therapy once daily for 4 days. The primary efficacy outcome is the change in infarct volume from baseline to day 5.

Conclusion: The ARISE trial will provide valuable evidence on the efficacy and safety of albumin in patients with AIS receiving EVT.

Clinical trial registration: www.clinicaltrials.gov, NCT06538844.

Keywords
albumin; neuroprotection; endovascular therapy; acute ischemic stroke

Background

Stroke is the most common cause of death and disability worldwide, with acute ischemic stroke (AIS) accounting for 80% of all cases (1, 2). Effective reperfusion therapies, such as intravenous thrombolysis and endovascular therapy (EVT), have been widely used in the treatment of AIS patients (3–5). While recanalization of occluded arteries is central to the treatment of AIS, patient prognosis may be further improved with additional treatment options that preserve and enhance brain function through neuroprotection (6, 7). Neuroprotective drugs can freeze the ischemic penumbra and target the ischemic cascade following cerebral infarction, including mechanisms such as oxidative stress and inflammation. This may reduce the inflammatory response, limit hemorrhagic transformation, and improve neurological prognosis after cerebral infarction (8, 9). However, neuroprotection in AIS has a long history of clinical trial failures over the past several decades (9, 10). One possible reason is that many of these drugs were not combined with reperfusion therapy (11, 12). Therefore, it is recommended that previously unsuccessful neuroprotective drugs, especially those supported by strong preclinical research evidence and confirmed to be safe in clinical studies, be reconsidered in the context of reperfusion therapy (9).

Albumin, the predominant protein in plasma, is mainly synthesized in the liver (13). Although the exact molecular mechanisms underlying albumin’s effects remain unclear, preclinical studies have shown its neuroprotective effects in several animal models of cerebral infarction. These effects include reducing cerebral edema through dehydration and increasing cerebral blood flow in ischemic areas (14–16). However, the Albumin in Acute Ischemic Stroke (ALIAS) trial, conducted from 2009 to 2012, did not confirm that high-dose albumin improves neurological prognosis in AIS patients (17). In this study, only 21% of participants received EVT. EVT devices and therapeutic techniques, along with the expansion of indications for EVT and the reduction of barriers to EVT selection through imaging, were not fully developed at the time of the study (17). The fact that neuroprotective treatment with albumin was not combined with efficient reperfusion therapy may have contributed to the failure of the study. Therefore, it is important to reevaluate the neuroprotective role of albumin in the context of reperfusion therapy for AIS.

This protocol describes the rationale and design of the ARISE (Albumin for Patients with Acute Large-Vessel Occlusive Stroke Undergoing Endovascular Therapy) trial, which aims to investigate albumin’s safety and efficacy for AIS patients undergoing EVT.

Methods

Ethical approval and informed consent

The clinical trial complies with the ethical guidelines outlined in the Declaration of Helsinki, which governs medical research involving human subjects. The ethics committees and institutional review boards of all participating clinical sites approved the study protocol. Prior to participation, written informed consent will be obtained from all participants or their legal guardians.

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Safety and efficacy of glibenclamide on functional outcomes in ischemic and hemorrhagic stroke: a systematic review and meta-analysis of randomized clinical trials

But NO protocol written up, so useless.

 Safety and efficacy of glibenclamide on functional outcomes in ischemic and hemorrhagic stroke: a systematic review and meta-analysis of randomized clinical trials

Ola Bin Shilash^1,2*Hussam Alhathlol^1,2Rana Alduhaysh^1,2Razan Almufarriji³Mohammed Bafaquh⁴

• ¹College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
• ²King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
• ³Department of Neurosurgery, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia
• ⁴Department of Neuro-Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Background: Secondary brain injuries, including delayed cerebral ischemia, neuroinflammation, and stroke induced cerebral edema can occur following both ischemic and hemorrhagic strokes, contributing to a negative impact on clinical outcomes. Glibenclamide, a sulfonylurea antidiabetic medication, has shown potential in minimizing these consequences by targeting the SUR1-TRPM4 channel. However, glibenclamide’s therapeutic effectiveness and safety in stroke patients remain unknown. Therefore, this systematic review aims to assess the safety and efficacy of glibenclamide in improving outcomes following both ischemic and hemorrhagic strokes.

Methods: Four databases were searched for RCTs published up to November 2024. Studies were included if they involved adult patients with ischemic stroke, hemorrhagic stroke, or subarachnoid hemorrhage, and reported relevant safety and efficacy outcomes. Efficacy outcomes were measured using the Modified Rankin Scale at 3 and 6 months. Safety outcomes included adverse events such as hypoglycemia, hydrocephalus, and mortality.

Results: Data from six RCTs, involving 555 patients (280 intervention, 275 control), were included: 4 trials in subarachnoid hemorrhage, one trial in ischemic stroke, and one in hemorrhagic stroke. At 3 months, the pooled odds ratio (OR) for poor functional outcomes was 0.98 (95% CI: 0.65–1.48), and at 6 months, 0.52 (95% CI: 0.24–1.12; p = 0.094), with no significant differences between glibenclamide and placebo. Safety analysis showed a significant increase in symptomatic hypoglycemia (OR 4.69, 95% CI: 1.45–15.23; p = 0.010) but no significant differences for hydrocephalus (OR 1.60, 95% CI: 0.76–3.37; p = 0.220) or mortality (OR 0.57, 95% CI: 0.32–1.05; p = 0.071). Delayed cerebral ischemia (DCI) showed a borderline reduction in risk (OR 0.43, 95% CI: 0.18–1.00; p = 0.051) in the treatment group.

Conclusion: In patients with ischemic or hemorrhagic stroke, glibenclamide demonstrates a favorable safety profile but shows limited efficacy in improving functional outcomes. The elevated risk of hypoglycemia emphasizes the necessity of using this medication with caution.

Introduction

Stroke remains one of the leading causes of morbidity and mortality globally, with an increasing burden due to rising incidents and prevalent cases over the past three decades (1). It is broadly categorized into ischemic stroke, caused by vascular occlusion, and hemorrhagic stroke, which includes intracerebral hemorrhage (ICH) (2). Despite advancements in acute stroke care, such as improved diagnostic tools and interventions, long-term outcomes remain suboptimal due to secondary complications like neuroinflammation, cerebral edema, and delayed neuronal injury (1, 2). This highlights the urgent need for novel therapeutic approaches targeting these mechanisms. Current treatments primarily concentrate on managing the acute phase, including reperfusion intervention (1, 2). Nevertheless, there is a considerable deficiency in therapies aimed at the molecular mechanisms that contribute to secondary injury (3). Glibenclamide, a well-known sulfonylurea antidiabetic medication, is one promising therapeutic approach. Glibenclamide works by blocking the sulfonylurea receptor 1 (SUR1)—transient receptor potential melastatin 4 (TRPM4) channel complex, which is essential in the pathophysiology of many central nervous system (CNS) injuries, including aSAH (4). The activation of the SUR1-TRPM4 channel has been linked to vasogenic edema, neuroinflammation aggravation, and neuronal integrity impairment. Glibenclamide, which targets this channel, has the ability to minimize cerebral edema, limit neuronal death, and reduce inflammation, therefore enhancing neurological recovery (5). Preclinical research has provided solid evidence for glibenclamide’s neuroprotective properties (6). In animal models of ischemic brain damage, glibenclamide treatment has been demonstrated to decrease vasogenic edema, reduce infarct volume, and enhance functional recovery (6). Building on this basis, preliminary clinical studies have assessed the function of glibenclamide in the setting of stroke. For example, recent research found that high-dose oral glibenclamide significantly reduced radiological indicators of cerebral edema during 10 days of therapy, implying possible advantages in preventing decompressive surgeries (7). Other trials, however, have shown conflicting results, with some failing to detect substantial increases in functional outcomes or decrease in mortality rates (3). While preliminary data suggests that it can minimize vasospasm and enhance perfusion, inconsistencies in research design, dosage regimens, and outcome measures have restricted the generalizability of findings (5). Furthermore, some concerns do exist about glibenclamide’s safety profile, including its possible impact on glucose homeostasis and other systemic side effects in non-diabetics (4, 8, 9).

To overcome these gaps, this systematic review and meta-analysis will analyze data from randomized controlled trials to assess the effectiveness and safety of glibenclamide in stroke. This study aims to clarify the influence of glibenclamide on major clinical outcomes.

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