Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-Like Effect in Stroke: Rationale, Design, and Protocol for a Prospective Randomized Controlled Trial

Shuyu Lv; Wenbo Zhao; Gary B Rajah; Chaitu Dandu; Lipeng Cai; Zhe Cheng; Honglian Duan; Qingqing Dai; Xiaokun Geng; Yuchuan Ding

doi:10.3389/fneur.2021.621476

Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-Like Effect in Stroke: Rationale, Design, and Protocol for a Prospective Randomized Controlled Trial

Front Neurol. 2021 Mar 17:12:621476. doi: 10.3389/fneur.2021.621476. eCollection 2021.

Authors

Shuyu Lv^{1

2}, Wenbo Zhao³, Gary B Rajah^{4

5}, Chaitu Dandu⁴, Lipeng Cai², Zhe Cheng², Honglian Duan², Qingqing Dai², Xiaokun Geng^{1

2

3

4}, Yuchuan Ding^{4

6}

Affiliations

¹ Luhe Institute of Neuroscience, Capital Medical University, Beijing, China.
² Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
³ China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.
⁴ Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States.
⁵ Department of Neurosurgery, Munson Medical Center, Traverse City, MI, United States.
⁶ Department of Research and Development Center, John D. Dingell VA Medical Center, Detroit, MI, United States.

Abstract

Background: Following an acute ischemic stroke (AIS), rapidly initiated reperfusion therapies [i. e., intravenous thrombolysis (IVT) and endovascular treatment (EVT)] demonstrate robust clinical efficacy. However, only a subset of these patients can benefit from these therapies due to their short treatment windows and potential complications. In addition, many patients despite successful reperfusion still have unfavorable outcomes. Thus, neuroprotection strategies are urgently needed for AIS patients. Chlorpromazine and promethazine (C+P) have been employed in clinical practice for antipsychotic and sedative purposes. A clinical study has also shown a neuroprotective effect of C+P on patients with cerebral hemorrhage and subarachnoid hemorrhage. The safety, feasibility, and preliminary efficacy of intravenous administration of C+P in AIS patients within 24 h of onset will be elucidated. Methods: A prospective randomized controlled trial is proposed with AIS patients. Participants will be randomly allocated to an intervention group and a control group with a 1:1 ratio (n = 30) and will be treated with standard therapies according to the current stroke guidelines. Participants allocated to the intervention group will receive intravenous administration of C+P (chlorpromazine 50 mg and promethazine 50 mg) within 24 h of symptom onset. The primary outcome is safety (mainly hypotension), while the secondary outcomes include changes in functional outcome and infarction volume. Discussions: This study on Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-like Effect in Stroke (RICHES) will be the first prospective randomized controlled trial to ascertain the safety, feasibility, and preliminary efficacy of intravenous C+P as a neuroprotection strategy in AIS patients. These results will provide parameters for future studies, provide insights into treatment effects, and neuroprotection with phenothiazine in AIS. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR2000038727.

Keywords: acute ischemic stroke (AIS); intravenous thrombolysis; neuroprotection; phenothiazine; rt-PA.