The Study of Ciprofol for the Suppression of Cardiovascular Responses to Tracheal Intubation

Intubation, Intratracheal Clinical Trial

Official title:

The Study of Ciprofol for the Suppression of Cardiovascular Responses to Tracheal

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06095570
• Other study ID #: RM20220701
• Status: Recruiting
• Phase: Phase 4
• Start date: July 23, 2022
• Est. completion date: December 30, 2023

Study information

• Verified date: September 2023
• Source: The Second Affiliated Hospital of Hainan Medical University
• Contact: Hu Sun
• Phone: 13617518996
• Email: sunhu09[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Preliminary studies have illuminated the promising nature of ciprofol, indicating its enhanced safety spectrum, superior potency, and a diminished likelihood of experiencing injection-related discomfort. Venturing deeper, this research embarked on an ambitious quest to measure the 95% effective volume of ciprofol for induction of general anesthesia by a modified sequential method and juxtapose the 95% effective volume dosage of ciprofol against a corresponding dose of remimazolam during the initiation of general anesthesia. The study delved into diverse anesthetic protocols, meticulously scrutinizing the safety and efficacy credentials of ciprofol. The ultimate vision was to pave a robust foundation for the sophisticated and judicious utilization of ciprofol in clinical landscapes.

Description:

During general anesthesia induction, tracheal intubation is a significant procedure that can cause cardiovascular fluctuations due to the stimulation of tracheal receptors. This can lead to complications such as imbalances in vital organ oxygen supply, especially in patients with cardiovascular and cerebrovascular disorders, potentially resulting in cardiac arrest. As the demand for anesthetics rises in clinical settings, some, due to extreme side effects, have been phased out, reducing the available options. Propofol, a common anesthetic, is effective and quick but has drawbacks like injection pain and risks associated with long-term use. In contrast, ciprofol, a new class I intravenous anesthetic, is emerging as a potentially better alternative. Early research indicates that ciprofol might have a broader safety margin than propofol and offers benefits like rapid recovery and lower chances of injection pain. Exhaustive studies on the precise dosage of ciprofol for surgical applications are scarce and comparisons between ciprofol and remimazolam are rarely reported in the literature. This research aims to bridge this knowledge gap, exploring the best dosage for tracheal intubation sedation, and ensuring patients get the most effective and safest anesthetic care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Patients undergoing surgery with a single-lumen endotracheal tube placed under general anesthesia;

2. American Society of Anesthesiologists(ASA grade) I or II;

3. Age 18~65 years old;

4. Body mass index (BMI) 18 to 28 kg/m2;

5. Mallampati airway classification grade I or II;

6. Acceptance of this experiment and signing of informed consent.

Exclusion Criteria:

1. Patients with a history of alcoholism, allergy to any component of the product;

2. Patients with severe heart, lung and brain vital organ diseases, such as acute heart attack, cerebral infarction, asthma, chronic obstructive pulmonary disease and other medical history;

3. Serious liver and kidney function abnormalities or combined serious endocrine dysfunction, such as hypertension (systolic blood pressure = 160 mmHg, diastolic blood pressure = 110 mmHg, HR = 110 beats/min), diabetes mellitus, hyperthyroidism, hypothyroidism and so on;

4. Difficult airway (mouth opening less than 3 cross fingers, those with Mallampati score grade III or IV, difficulty in vocal valve exposure, difficulty in tracheal intubation, unsuccessful in one attempt); oropharyngeal and cervical deformities or history of previous tracheotomy;

5. Neuropsychiatric abnormalities, communication and comprehension deficits exist;

6. History of long-term sedative and analgesic medications, drug and opioid addiction, and heart rate control medications (e.g., beta blockers, alpha agonists, calcium channel blockers); and

7. Pregnancy.

Related Conditions & MeSH terms

• Adverse Effects
• Intubation, Intratracheal

Intervention

Drug:
• Ciprofol
For induction of anesthesia, an experimental dose of ciprofol was given, and when the patient lost consciousness and the Modified Observer's Alertness/Sedation scale(MOAA/S score) was less than 1, then intravenous sufentanil and rocuronium bromide were administered, and tracheal intubation was performed 3 minutes later
• Remimazolam
For induction of anesthesia, an experimental dose of remimazolam was given, and when the patient lost consciousness and the Modified Observer's Alertness/Sedation scale(MOAA/S score) was less than 1, then intravenous sufentanil and rocuronium bromide were administered, and tracheal intubation was performed 3 minutes later

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Hainan Medical University, Hai Kou, China	Haikou	Hainan

Sponsors (1)

Lead Sponsor	Collaborator
The Second Affiliated Hospital of Hainan Medical University

Country where clinical trial is conducted

China, 

References & Publications (9)

Bian Y, Zhang H, Ma S, Jiao Y, Yan P, Liu X, Ma S, Xiong Y, Gu Z, Yu Z, Huang C, Miao L. Mass balance, pharmacokinetics and pharmacodynamics of intravenous HSK3486, a novel anaesthetic, administered to healthy subjects. Br J Clin Pharmacol. 2021 Jan;87(1):93-105. doi: 10.1111/bcp.14363. Epub 2020 Aug 3. — View Citation

El-Shmaa NS, El-Baradey GF. The efficacy of labetalol vs dexmedetomidine for attenuation of hemodynamic stress response to laryngoscopy and endotracheal intubation. J Clin Anesth. 2016 Jun;31:267-73. doi: 10.1016/j.jclinane.2016.01.037. Epub 2016 Apr 18. — View Citation

Hemphill S, McMenamin L, Bellamy MC, Hopkins PM. Propofol infusion syndrome: a structured literature review and analysis of published case reports. Br J Anaesth. 2019 Apr;122(4):448-459. doi: 10.1016/j.bja.2018.12.025. Epub 2019 Feb 6. — View Citation

Higgs A, McGrath BA, Goddard C, Rangasami J, Suntharalingam G, Gale R, Cook TM; Difficult Airway Society; Intensive Care Society; Faculty of Intensive Care Medicine; Royal College of Anaesthetists. Guidelines for the management of tracheal intubation in critically ill adults. Br J Anaesth. 2018 Feb;120(2):323-352. doi: 10.1016/j.bja.2017.10.021. Epub 2017 Nov 26. — View Citation

Kayhan Z, Aldemir D, Mutlu H, Ogus E. Which is responsible for the haemodynamic response due to laryngoscopy and endotracheal intubation? Catecholamines, vasopressin or angiotensin? Eur J Anaesthesiol. 2005 Oct;22(10):780-5. doi: 10.1017/s0265021505001298. — View Citation

Qin L, Ren L, Wan S, Liu G, Luo X, Liu Z, Li F, Yu Y, Liu J, Wei Y. Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics. J Med Chem. 2017 May 11;60(9):3606-3617. doi: 10.1021/acs.jmedchem.7b00254. Epub 2017 Apr 28. — View Citation

Sneyd JR, Absalom AR, Barends CRM, Jones JB. Hypotension during propofol sedation for colonoscopy: a retrospective exploratory analysis and meta-analysis. Br J Anaesth. 2022 Apr;128(4):610-622. doi: 10.1016/j.bja.2021.10.044. Epub 2021 Dec 13. — View Citation

Weisenberg M, Sessler DI, Tavdi M, Gleb M, Ezri T, Dalton JE, Protianov M, Zimlichmann R. Dose-dependent hemodynamic effects of propofol induction following brotizolam premedication in hypertensive patients taking angiotensin-converting enzyme inhibitors. J Clin Anesth. 2010 May;22(3):190-5. doi: 10.1016/j.jclinane.2009.07.008. — View Citation

Xue FS, Xu YC, Liu Y, Yang QY, Liao X, Liu HP, Zhang YM, Liu JH, Luo MP. Different small-dose sufentanil blunting cardiovascular responses to laryngoscopy and intubation in children: a randomized, double-blind comparison. Br J Anaesth. 2008 May;100(5):717-23. doi: 10.1093/bja/aen032. Epub 2008 Mar 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Heart Rate(HR)	Heart rate monitored with Dash4000 equipment	Intravenous ciprofol up to 3 minutes after tracheal intubation
Primary	Mean Arterial Pressure(MAP)	Heart rate monitored with Dash4000 equipment	Intravenous ciprofol up to 3 minutes after tracheal intubation
Secondary	Bispectral Index(BIS)	Monitored woth Bispectral Index Vista. BIS ranges from 0-100, with 100 representing full wakefulness and 0 representing complete cortical electroencephalogram(EEG) suppression; the smaller the value, the deeper the depth of sedation Mild sedation is BIS 65-85, and deep sedation is BIS 40-60, with primitive EEG bursts of suppression when BIS < 40.	Intravenous ciprofol up to 3 minutes after tracheal intubation
Secondary	Peripheral Oxygen Saturation(SPO2)	Monitored with Dash4000 equipment	Intravenous ciprofol up to 3 minutes after tracheal intubation
Secondary	Rate of respiratory inhibition,Injection pain,Hypotension,Allergy,Bradycardia,Muscle tremor,Postoperative nausea and vomiting	Referring to the standards in ciprofol's Phase III trial, the adverse reactions were defined as follows: (1) hypoxemia (oxygen saturation < 90% for > 30 s); (2) bradycardia (HR < 45/min for > 30 s); (3) hypotension (systolic BP decreased by 30% from the baseline value for > 2 min); and (4) pain at the injection site during ciprofol administration, evaluated by a study-blinded investigator using a 4-point verbal rating scale.	Intravenous ciprofol to leave resuscitation