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

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

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 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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