Efficacy and safety of ciprofol for agitation and delirium in the ICU: A multicenter, single-blind, 3-arm parallel randomized controlled trial study protocol

Guo Liang Liu; Guo Zhi Wu; Dong Ge; Heng Jie Zhou; Song Cui; Kai Gao; Wei Jia Sun; Dong Hai Yu; Si Bo Liu; Jin Jie Liu

doi:10.3389/fmed.2022.1024762

Efficacy and safety of ciprofol for agitation and delirium in the ICU: A multicenter, single-blind, 3-arm parallel randomized controlled trial study protocol

Front Med (Lausanne). 2023 Jan 9:9:1024762. doi: 10.3389/fmed.2022.1024762. eCollection 2022.

Authors

Guo Liang Liu¹, Guo Zhi Wu¹, Dong Ge¹, Heng Jie Zhou¹, Song Cui¹, Kai Gao¹, Wei Jia Sun², Dong Hai Yu³, Si Bo Liu^{1

4}, Jin Jie Liu^{5

6}

Affiliations

¹ Intensive Care Unit, Dalian Municipal Central Hospital Affiliated Dalian University of Technology, Dalian, China.
² Department of Pharmacy, Dalian Municipal Central Hospital Affiliated Dalian University of Technology, Dalian, China.
³ Department of Anesthesiology, Dalian Municipal Central Hospital Affiliated Dalian University of Technology, Dalian, China.
⁴ Intensive Care Unit, Beijing Friendship Hospital Affiliated Capital Medical University, Beijing, China.
⁵ Department of NO.2 General Medicine, Dalian Municipal Central Hospital Affiliated Dalian University of Technology, Dalian, China.
⁶ Neurological Intensive Care Unit, Beijing Tiantan Hospital Affiliated Capital Medical University, Beijing, China.

Abstract

Background: Agitation is very common in the intensive care unit (ICU). The causes include pain, delirium, underlying disease, withdrawal syndrome, and some drug treatments. The practical goal of ICU treatment is to find an appropriate sedation regimen to reduce pain, restlessness, and delirium. Previous trials have examined the use of dexmedetomidine, but no trials have evaluated the efficacy and safety of ciprofol, a new sedative drug.

Methods: This study was a multicenter, single-blind, 3-arm parallel randomized controlled trial. ICU patients aged ≥ 18 years with agitation and delirium who met the eligibility criteria were included. The main outcome was the proportion of patients who needed additional study medication or midazolam due to agitation within 4 h after the first intravenous injection of the study medication. The secondary outcomes included the pass rate as indicated by a Richmond Agitation-Sedation Scale (RASS) score < +1, the effectiveness rate of improving delirium symptoms, the number of recurrences of agitation within 24 h, the incidence of rescue treatment, the dose and cost of analgesic and sedative drugs, the length and cost of ICU stay, and the 30-day survival period. The safety evaluation included the incidence of adverse events (hypotension, bradycardia, hypoxia, etc.) and the rate of endotracheal intubation. The subjects were randomly assigned to receive ciprofol, dexmedetomidine, or normal saline at a ratio of 1:1:1. The rates of additional drug administration within 4 h after the first injection of the study drug in the three groups were 40, 50, and 90%, respectively. A total sample size of 81 subjects was required to reach 90% power and an α of 0.05. Considering a 20% loss rate, 102 patients were enrolled and randomly assigned to the three groups in equal proportions.

Ethics and communication: This trial was approved by the Ethics Committee of Dalian Municipal Central Hospital. The communication plan includes presentations at scientific conferences, scientific publications, and presentations to the public through non-professional media.

Clinical trial registration: www.ClinicalTrials.gov, identifier ChiCTR220006 2799.

Keywords: agitation; ciprofol; delirium; intensive care unit; sedation.

Grants and funding

This work was supported by the Dalian High-Level Talents Innovation Support Plan (grant number 2021RQ029) and the Open Project Program of Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education (grant number 2019GDND03).