Dataset Information

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

ABSTRACT:

Objectives

To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV).

Design

A multicenter, single-blind, randomized, noninferiority trial.

Setting

Twenty-one centers across China from December 2020 to June 2021.

Patients

A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6-24 hours.

Interventions

One hundred thirty-five ICU patients were randomly allocated into ciprofol ( n = 90) and propofol ( n = 45) groups in a 2:1 ratio. Ciprofol or propofol were IV infused at loading doses of 0.1 mg/kg or 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol or propofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr or 1.5 mg/kg/hr, to achieve the target sedation range of Richmond Agitation-Sedation Scale (+1 to -2). Besides, continuous IV remifentanil analgesia was administered (loading dose: 0.5-1 μg/kg, maintenance dose: 0.02-0.15 μg/kg/min).

Measurements and main results

Of the 135 patients enrolled, 129 completed the study. The primary endpoint-sedation success rates of ciprofol and propofol groups were 97.7% versus 97.8% in the full analysis set (FAS) and were both 100% in per-protocol set (PPS). The noninferiority margin was set as 8% and confirmed with a lower limit of two-sided 95% CI for the inter-group difference of -5.98% and -4.32% in the FAS and PPS groups. Patients who received ciprofol had a longer recovery time ( p = 0.003), but there were no differences in the remaining secondary endpoints (all p > 0.05). The occurrence rates of treatment-emergent adverse events (TEAEs) or drug-related TEAEs were not significantly different between the groups (all p > 0.05).

Conclusions

Ciprofol was well tolerated, with a noninferior sedation profile to propofol in Chinese ICU patients undergoing MV for a period of 6-24 hours.

SUBMITTER: Liu Y

PROVIDER: S-EPMC10497206 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

Liu Yongjun Y Peng Zhiyong Z Liu Songqiao S Yu Xiangyou X Zhu Duming D Zhang Linlin L Wen Jianli J An Youzhong Y Zhan Liying L Wang Xiaochuang X Kang Yan Y Pan Aijun A Yan Jing J Zhang Lina L Liu Fengming F Zeng Jun J Lin Qinhan Q Sun Renhua R Yu Jiangquan J Wang Huaxue H Yao Li L Chen Chuanxi C Liu Ning N Nie Yao Y Lyu Jie J Wu Kun K Wu Jianfeng J Liu Xiao X Guan Xiangdong X

Critical care medicine 20230605 10

<h4>Objectives</h4>To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV).<h4>Design</h4>A multicenter, single-blind, randomized, noninferiority trial.<h4>Setting</h4>Twenty-one centers across China from December 2020 to June 2021.<h4>Patients</h4>A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6-24 hours.<h4>Interventions</h4>One hundred ...[more]

PMID: 37272947

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Project description:IntroductionFrom previous studies of pharmacodynamic data in mice, rats, beagle dogs and mini pigs, frequently in direct comparison to induction doses of propofol, ciprofol produced a rapid onset of anesthesia/sedation.MethodsA phase 1 study suggested potential clinical advantages of ciprofol as a sedation/anesthetic agent, with no evidence of drug-related toxicity. However, the sedation effects and safety of ciprofol in intensive care unit (ICU) patients with mechanical ventilation should be further confirmed in a phase 3 study with a larger cohort of patients. During a phase 3, non-inferiority, multicenter, single-blind, randomized, propofol controlled trial, Chinese ICU patients undergoing mechanical ventilation and requiring endotracheal intubation will be sedated for 6-24 h after randomization. Considering a success rate for ICU sedation of 99% for ciprofol and the positive control drug propofol, a total sample size of 120 subjects with mechanical ventilation will be required to achieve 80% power to determine non-inferiority with a margin of 8%. Finally, taking into account 10% losses, 135 patients will be enrolled and randomly assigned to ciprofol (90 cases) and propofol (45 cases) groups in a 2:1 ratio. The primary outcome will be the success rate of sedation satisfied by the following conditions: the time within the range of Richmond Agitation and Sedation Score (+ 1 ~ - 2) must account for ≥ 70% of the study drug administration time and without other rescue treatments. Secondary outcomes will include the average time to reach the sedation goal, study drug usage, rescue medication given per unit weight, extubation time, recovery time to full consciousness and nursing scores. Safety endpoints will include adverse events (AEs), drug related AEs and serious AEs.Planned outcomesThe results of this study will provide crucial information on the use of ciprofol for sedation of patients in ICUs.Trial registrationClinicalTrials.gov identifier, NCT04620031.

Project description:BackgroundCiprofol (HSK3486; Haisco Pharmaceutical Group Co., Ltd., Chengdu, China), developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial. The phase 2 trial was designed to investigate the safety, efficacy, and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation.MethodsIn this multicenter, open label, randomized, propofol positive-controlled, phase 2 trial, 39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio. The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 0.30 mg·kg -1 ·h -1 , which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg -1 ·h -1 , whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 1.50 mg·kg -1 ·h -1 , which could be adjusted to 0.30-4.00 mg·kg -1 ·h -1 to achieve -2 to +1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration.ResultsOf the 39 enrolled patients, 36 completed the trial. The median (min, max) of the average time to sedation compliance values for ciprofol and propofol were 60.0 (52.6, 60.0) min and 60.0 (55.2, 60.0) min, with median difference of 0.00 (95% confidence interval: 0.00, 0.00). In total, 29 (74.4%) patients comprising 18 (69.2%) in the ciprofol and 11 (84.6%) in the propofol group experienced 86 treatment emergent adverse events (TEAEs), the majority being of severity grade 1 or 2. Drug- and sedation-related TEAEs were hypotension (7.7% vs. 23.1%, P = 0.310) and sinus bradycardia (3.8% vs. 7.7%, P = 1.000) in the ciprofol and propofol groups, respectively. The plasma concentration-time curves for ciprofol and propofol were similar.Conclusionsciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting.Trial registrationClinicalTrials.gov, NCT04147416.

Project description:Background: Ciprofol (HSK3486) is a novel intravenous anesthetic agent that bears structural similarity to propofol and displays favorable pharmacodynamic characteristics such as rapid onset and offset. The meta-analysis aimed at comparing the efficacy and safety of ciprofol versus propofol in clinical practice. Methods: Medline, EMBASE, Google Scholar, Cochrane Library were searched from inception to April 2023. The primary outcome was success rate of sedation/anesthetic induction and differences in sedation/induction time. The secondary outcomes included risks of hemodynamic instability, respiratory complications, and pain on injection, as well as recovery profiles, satisfaction score, and top-up dose requirement. Results: Twelve RCTs (sedation: n = 6, anesthetic induction, n = 6, all conducted in China) involving 1,793 patients (age: 34-58 years) published from 2021 to 2023 were analyzed. Pooled results revealed no differences in success rate [risk ratio (RR) = 1, 95% confidence interval (CI): 0.99 to 1.01, I2 = 0%, 1,106 patients, p = 1] and time required for successful anesthetic induction/sedation [mean difference (MD) = 7.95 s, 95% CI: -1.09 to 16.99, I2 = 97%, 1,594 patients, p = 0.08]. The risks of top-up dose requirement (RR = 0.94, p = 0.48), cardiopulmonary complications [i.e., bradycardia (RR = 0.94, p = 0.67), tachycardia (RR = 0.83, p = 0.68), hypertension (RR = 1.28, p = 0.2), hypoxemia/pulmonary depression (RR = 0.78, p = 0.24)], and postoperative nausea/vomiting (RR = 0.85, p = 0.72), as well as discharge time (MD = 1.39 min, p = 0.14) and satisfaction score (standardized MD = 0.23, p = 0.16) did not differ significantly between the two groups. However, the ciprofol group had lower risks of hypotension (RR = 0.85, p = 0.02) and pain on injection (RR = 0.17, p < 0.00001) than the propofol group. The time to full alertness was statistically shorter in the propofol group (i.e., 0.66 min), but without clinical significance. Conclusion: Our results demonstrated similar efficacy between ciprofol and propofol for sedation and anesthetic induction, while ciprofol was associated with lower risks of hypotension and pain on injection. Future studies are warranted to evaluate the efficacy and safety of ciprofol in pediatric or the elderly populations. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/), identifier (CRD42023421278).

Project description:BackgroundCiprofol was approved for use in intensive care unit (ICU) patients requiring sedation during mechanical ventilation in July 2022. A pooled post-hoc analysis of phase 2 and phase 3 trials was conducted primarily to explore hypotension-free outcome in ICU patients who required mechanical ventilation and achieved the target light sedation goal at an early stage after being sedated with ciprofol or propofol.MethodsAll eligible ICU patients who were expected to require sedation for 6-24 h were randomly assigned in a 2:1 ratio to either a ciprofol or propofol group. Ciprofol or propofol was initially infused at loading doses of 0.5 or 1.0 mg/kg followed by maintenance doses of 0.3 or 1.5 mg/kg/h. Ciprofol or propofol dosages were adjusted up or down at rates of 0.05-0.10 mg/kg/h or 0.25-0.50 mg/kg/h, respectively, to achieve the target light sedation (a Richmond Agitation-Sedation Scale of -2 to + 1). The primary post-hoc outcome was the hypotension-free rate in patients who had achieved the target sedation goal after 30-min administration of ciprofol or propofol.ResultsIn total, 174 patients were enrolled for pooled post-hoc analysis, of whom 116 and 58 were assigned to the ciprofol and propofol groups, respectively. The hypotension-free rate was significantly higher in patients who achieved the target sedation goal after 30-min administration of ciprofol (93.0% vs. 81.0%, P = 0.018), and especially in the subgroups of males and patients aged < 65 years. Multivariable analysis revealed that ciprofol treatment, a younger age and lower baseline body mass index were independent favorable predictors for a higher hypotension-free rate in patients who achieved the target sedation goal after 30-min of drug administration. Moreover, hypotension-free patients who reached the target sedation level after 30 min had a more favorable short-term prognosis including a lower incidence of drug-related treatment-emergent adverse events, shorter time to extubation and fewer dose adjustments of ciprofol or propofol (all P < 0.05).ConclusionICU patients undergoing mechanical ventilation and sedated with ciprofol had significantly lower rate of hypotension during the early phase of achieving light sedation during a 6-24 h period, leading to a more favorable short-term prognosis (within 24 h).Trial registrationPhase 2 trial (clinicaltrials.gov, NCT04147416. Registered November 1, 2019, https://classic.Clinicaltrialsgov/ct2/show/NCT04147416 ) and phase 3 trial (clinicaltrials.gov, NCT04620031. Registered November 6, 2020, https://classic.Clinicaltrialsgov/ct2/show/NCT04620031 ).

Project description:BackgroundAlthough light sedation levels are associated with several beneficial outcomes for critically ill patients on mechanical ventilation, the majority of patients are still deeply sedated. Organizational factors may play a role on adherence to light sedation levels. We aimed to identify organizational factors associated with a moderate to light sedation target on the first 48 h of mechanical ventilation, as well as the association between early achievement of within-target sedation and mortality.MethodsThis study is a secondary analysis of a multicenter two-phase study (prospective cohort followed by a cluster-randomized controlled trial) performed in 118 Brazilian ICUs. We included all critically ill patients who were on mechanical ventilation 48 h after ICU admission. A moderate to light level of sedation or being alert and calm (i.e., the Richmond Agitation-Sedation Scale of - 3 to 0) was the target for all patients on mechanical ventilation during the study period. We collected data on the type of hospital (public, private, profit and private, nonprofit), hospital teaching status, nursing and physician staffing, and presence of sedation, analgesia, and weaning protocols. We used multivariate random-effects regression with ICU and study phase as random-effects and correction for patients' Simplified Acute Physiology Score 3 and Sequential Organ Failure Assessment. We also performed a mediation analysis to explore whether sedation level was just a mediator of the association between organizational factors and mortality.ResultsWe included 5719 patients. Only 1710 (29.9%) were on target sedation levels on day 2. Board-certified intensivists on the morning and afternoon shifts were associated with an adequate sedation level on day 2 (OR = 2.43; CI 95%, 1.09-5.38). Target sedation levels were associated with reduced hospital mortality (OR = 0.63; CI 95%, 0.55-0.72). Mediation analysis also suggested such an association, but did not suggest a relationship between the physician staffing model and hospital mortality.ConclusionsBoard-certified intensivists on morning and afternoon shifts were associated with an increased number of patients achieving lighter sedation goals. These findings reinforce the importance of organizational factors, such as intensivists' presence, as a modifiable quality improvement target.

Dataset Information

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

Objectives

Design

Setting

Patients

Interventions

Measurements and main results

Conclusions

Publications

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

Similar Datasets

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