Oliceridine vs Sufentanil for Cough During Anesthesia Induction

Oliceridine vs Sufentanil for Cough During General Anesthesia Induction: A Randomized Controlled Trial

Sufentanil is the most widely used opioid analgesic for general anaesthesia induction; however, rapid intravenous bolus injection frequently triggers sufentanil-induced cough (SIC). In high-risk patients, SIC can cause abrupt elevation of intracranial and intraocular pressure and severe haemodynamic instability, posing a meaningful safety risk during the induction period.

Oliceridine, the first G protein-biased μ-opioid receptor agonist approved by the Food and Drug Administration in 2020, provides analgesia through μ-receptor activation while substantially reducing β-arrestin-2 recruitment. This biased signalling profile is hypothesised to raise the excitation threshold of airway C-fibres and thereby reduce the incidence of cough.

This prospective, single-centre, randomised, double-blind, parallel-group controlled trial directly compares oliceridine with sufentanil for general anaesthesia induction with respect to cough incidence, cough severity, haemodynamic responses, and perioperative safety, with the aim of providing evidence-based guidance for opioid selection during induction.

Study Overview

• Status: Not yet recruiting
• Conditions: Cough; Anesthesia
• Intervention / Treatment: Drug: Oliceridine; Drug: Sufentanil

Detailed Description

Rapid intravenous bolus injection of sufentanil frequently triggers sufentanil-induced cough (SIC). Although several prophylactic strategies have been described, all rely on adding a pretreatment agent on top of sufentanil - a reactive, patch-based approach that does not address the underlying cause. Oliceridine, a G protein-biased μ-opioid receptor agonist, preserves analgesic efficacy while substantially reducing β-arrestin-2 recruitment. This biased signalling profile is hypothesised to reduce cough risk at its origin by maintaining normal desensitisation of airway C-fibre transient receptor potential vanilloid 1 (TRPV1) channels and preserving β₂-adrenergic receptor-mediated bronchodilatory reserve in airway smooth muscle. Furthermore, oliceridine is formulated as a fumarate salt; because conventional fentanyl-class agents use citrate formulations, this difference eliminates a potential chemical cough stimulus at the formulation level. This prospective, single-centre, randomised, double-blind, parallel-group controlled trial directly compares oliceridine with sufentanil for general anaesthesia induction. A randomisation sequence will be generated by an independent statistician and concealed using sealed opaque envelopes; both the attending anaesthesiologist and the data recorder will remain blinded to group allocation throughout the study. Participants in the oliceridine group will receive intravenous oliceridine 0.05 mg/kg (elderly patients) or 0.06 mg/kg (younger patients) as a 2-second bolus, whereas participants in the sufentanil group will receive intravenous sufentanil 0.4 μg/kg (elderly patients) or 0.5 μg/kg (younger patients) as a 2-second bolus. Cough will be observed for 2 minutes after injection, after which anaesthesia induction will be completed with propofol 2.0 mg/kg followed by rocuronium 0.6 mg/kg, and tracheal intubation will be performed. The primary outcome is the incidence of cough within 2 minutes of study drug injection. Secondary outcomes include cough severity (mild, moderate, or severe); haemodynamic variables - heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure - at time points T0 through T5; incidence of haemodynamic adverse events, including bradycardia and hypotension; and opioid-related adverse events, including chest wall rigidity, apnoea, and arterial oxygen saturation below 95%. Assuming a cough incidence of 40% in the sufentanil group and an expected reduction to 10% in the oliceridine group, with a two-sided α of 0.05 and 80% power, 30 participants per group are required; accounting for a 5% dropout rate, 31 participants will be enrolled per group, for a total of 62 participants. The trial will be conducted in the Department of Anaesthesiology, Tianmen First People's Hospital, Tianmen, Hubei, China (a tertiary Grade-A hospital).

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Shiyou Wei, MD.; Phone Number: 15601680288; Email: lovewishyou@tongji.edu.cn

Study Locations

• China
  • Hubei
    • Tianmen, Hubei, China, 431700
      • Tianmen First People's Hospital
      • Contact: Jianmang Yu, Doc; Phone Number: 8613094293728; Email: yujianmang@hbust.edu.cn
      • Contact: Zhixiong Xiang, Doc; Phone Number: 86-0728-5237400; Email: 28612363@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 to 99 years.
• American Society of Anesthesiologists (ASA) physical status classification I, II, or III.
• Body mass index (BMI) between 18.5 and 28.0 kg/m².
• Scheduled for elective surgery under general anaesthesia.
• Able to understand the study procedures and provide written informed consent.

Exclusion Criteria:

• Preoperative upper respiratory tract infection symptoms (e.g., cough, expectoration, or fever) or a history of bronchial asthma or other conditions associated with increased airway reactivity.
• Severe cardiovascular disease (e.g., uncontrolled hypertension, recent myocardial infarction, or serious arrhythmia) or hepatic or renal dysfunction.
• Long-term opioid use, defined as continuous opioid use for more than 2 weeks within the 3 months prior to surgery.
• Known hypersensitivity to any study drug or anaesthetic agent used in this protocol.
• Anticipated difficult airway requiring awake intubation.
• Pregnancy or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oliceridine Group; Participants will receive intravenous oliceridine 0.05 mg/kg (elderly patients aged ≥65 years) or 0.06 mg/kg (younger patients aged 18-64 years), administered as a 2-second bolus injection. Cough will be observed for 2 minutes after injection, after which anaesthesia induction will be completed with propofol and rocuronium , followed by tracheal intubation.	Drug: Oliceridine; Oliceridine is administered as a single intravenous bolus over 2 seconds at a dose of 0.05 mg/kg in elderly patients (aged ≥65 years) or 0.06 mg/kg in younger patients (aged 18-64 years), immediately before propofol and rocuronium for anaesthesia induction.; Other Names: TRV130; Oliceridine Fumarate
Active Comparator: Sufentanil Group; Participants will receive intravenous sufentanil 0.4 μg/kg (elderly patients aged ≥65 years) or 0.5 μg/kg (younger patients aged 18-64 years), administered as a 2-second bolus injection. Cough will be observed for 2 minutes after injection, after which anaesthesia induction will be completed with propofol and rocuronium , followed by tracheal intubation.	Drug: Sufentanil; Sufentanil is administered as a single intravenous bolus over 2 seconds at a dose of 0.4 μg/kg in elderly patients (aged ≥65 years) or 0.5 μg/kg in younger patients (aged 18-64 years), immediately before propofol and rocuronium for anaesthesia induction.; Other Names: Sufentanil Citrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Cough	The proportion of participants who cough at least once within 2 minutes of study drug injection. Cough is defined as a sudden, forceful expiratory effort occurring after drug administration and assessed by direct observation.	Within 2 minutes of study drug injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cough Severity	Cough severity is graded on a three-point scale: mild (1-2 coughs), moderate (3-4 coughs or sustained cough lasting <5 seconds), or severe (≥5 coughs or sustained cough lasting ≥5 seconds).	Within 2 minutes of study drug injection.
Heart rate	Heart rate recorded at baseline, immediately after drug injection, and at 1, 2, 3, and 5 minutes after injection .	From entry into the operating room to 10 minutes after administration of the study drug.
Blood pressure	Systolic blood pressure, diastolic blood pressure, and mean arterial pressure recorded at baseline, immediately after drug injection, and at 1, 2, 3, and 5 minutes after injection .	From entry into the operating room to 10 minutes after administration of the study drug.
Opioid-related Adverse Events	Incidence of chest wall rigidity, apnoea, and arterial oxygen saturation below 92% occurring after study drug injection and before tracheal intubation.	From study drug injection to completion of tracheal intubation, approximately 10 minutes.

Collaborators and Investigators

• Sponsor: Shiyou Wei
• Collaborators: Tianmen First People's Hospital
• Investigators: Study Chair: Shiyou Wei, Tongji University Affiliated Shanghai Pulmonary Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 25, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: June 14, 2026
• First Submitted That Met QC Criteria: June 17, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Sufentanil; Anesthesia induction; Oliceridine; Sufentanil-induced cough; G protein-biased agonist
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Cough; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines; Fentanyl; Sufentanil; ((3-methoxythiophen-2-yl)methyl)((2-(9-(pyridin-2-yl)-6-oxaspiro(4.5)decan-9-yl)ethyl))amine
• Other Study ID Numbers: Tianmen20260009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No