Oliceridine Dose for Tracheal Intubation Hemodynamic Elevation: Up-and-Down Trial

NCT ID: NCT07154979

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-04
• Study Completion Date: 2025-09-11

Brief Summary

This is a clinical trial using an up-and-down sequential design, aiming to investigate the median effective dose (ED50) and 95% effective dose (ED95) of oliceridine for inhibiting hyperdynamic responses induced by tracheal intubation during general anesthesia induction. The study will enroll patients undergoing elective tracheal intubation under general anesthesia, stratified into young (18-65 years) and elderly (≥65 years) groups. By dynamically adjusting oliceridine doses, the optimal induction dose in different age groups will be evaluated to provide reference for rational clinical medication.

Detailed Description

1. Study Objectives To determine the ED50 and ED95 of oliceridine in inhibiting tracheal intubation-induced hyperdynamic responses (e.g., increased blood pressure and heart rate) during general anesthesia induction, and to provide dose evidence for individualized anesthesia induction protocols.

2. Study Design Type: A dynamic dose-finding clinical trial using the modified Dixon up-and-down sequential design.

Sample Size: 35 cases per group anticipated, with trial termination after 7 cross-overs between positive and negative responses (i.e., transitions in whether hemodynamic responses exceed 20% of baseline).

Grouping: Stratified by age into young group (18-65 years) and elderly group (≥65 years).

3. Study Participants

Inclusion Criteria:

Patients undergoing elective tracheal intubation under general anesthesia; Aged ≥18 years; American Society of Anesthesiologists (ASA) physical status Ⅰ-Ⅲ; Body mass index (BMI) < 25.

Exclusion Criteria:

Systolic blood pressure (SBP) ≥160 mmHg, diastolic blood pressure (DBP) ≥110 mmHg, or heart rate ≥110 beats/min at rest upon admission to the operating room; Long-term use of analgesics or sedatives before surgery; Pregnancy, lactation, or planned pregnancy; Allergy to oliceridine; Mental illness or inability to communicate normally.

4. Trial Procedures Screening Period (-7 to 0 days): Informed consent signed; collection of basic information (age, ASA class, etc.); baseline blood pressure and heart rate monitored.

Anesthesia Induction and Intubation:

Routine vital sign monitoring and intravenous access established upon patient admission.

Initial doses: 45 μg/kg for the young group and 42 μg/kg for the elderly group. Subsequent doses adjusted based on intubation response (increase by 3 μg/kg for positive response, decrease by 3 μg/kg for negative response).

Administration sequence: Intravenous oliceridine → propofol 2 mg/kg 2 minutes later → rocuronium 0.6 mg/kg after loss of consciousness (MOAA/S score ≤1) → tracheal intubation after neuromuscular blockade.

Anesthesia Maintenance: Propofol (4-8 mg/kg/h) and remifentanil (0.05-0.1 μg/kg/min) infused continuously; rocuronium added intermittently; protective ventilation strategy applied.

5. Outcome Measures Primary Measures: ED50 and ED95 of oliceridine for inhibiting post-intubation hyperdynamic responses.

Secondary Measures:

Incidence of hyperdynamic responses within 3 minutes after intubation; Blood pressure (SBP, DBP) and heart rate at baseline, 2 minutes after drug administration, before intubation, and within 3 minutes after intubation; Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score; Adverse events (arrhythmia, coughing, allergic reactions, etc.).

6. Statistical Methods Data analysis will be performed using R software. Quantitative data will be expressed as mean±standard deviation or median (interquartile range), and qualitative data as frequency (percentage). Probit analysis will be used to calculate ED50 and its 95% confidence interval. A P-value <0.05 will be considered statistically significant.

Conditions

Oliceridine

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oliceridine Up-and-Down Sequential Dose-Finding Arm

In this single-group, up-and-down sequential design, adult patients receive a single intravenous bolus of oliceridine.

• Initial dose: 45 µg/kg for ages 18-65 years; 40 µg/kg for ≥ 65 years
• Two minutes later: propofol 2 mg/kg iv
• At loss of consciousness (MOAA/S ≤ 1): rocuronium 0.6 mg/kg iv
• Direct-laryngoscope tracheal intubation performed upon full muscle relaxation
• Hemodynamic variables (BP, HR) recorded at baseline, 2 min post-oliceridine, immediately pre-intubation, and for 3 min post-intubation
• A "positive" response (hemodynamic surge) is defined as ≥ 20% increase in MAP or HR, HR ≥ 120 bpm, or SBP ≥ 180 mmHg
• Next patient's oliceridine dose is adjusted ± 3 µg/kg according to the preceding patient's response
• Sequential dosing continues until seven crossovers are observed, allowing estimation of ED₅₀ and ED₉₅.

Group Type: EXPERIMENTAL

Oliceridine Injection

Intervention Type: DRUG

Adult participants receive a single IV bolus of oliceridine (initial dose 45 µg/kg for ages 18-65 y or 40 µg/kg for ≥65 y). Two minutes later, propofol 2 mg/kg IV is administered. Upon loss of consciousness (MOAA/S ≤ 1), rocuronium 0.6 mg/kg IV is given. Direct laryngoscopic tracheal intubation is performed after full muscle relaxation. Blood pressure and heart rate are recorded at baseline, 2 min post-oliceridine, immediately pre-intubation, and for 3 min post-intubation. A "positive" hemodynamic response is defined as ≥ 20% increase in MAP or HR, HR ≥ 120 bpm, or SBP ≥ 180 mmHg. Subsequent oliceridine doses are adjusted ± 3 µg/kg based on the prior patient's response until seven response crossovers are observed, allowing estimation of ED₅₀ and ED₉₅.

Interventions

Oliceridine Injection

Adult participants receive a single IV bolus of oliceridine (initial dose 45 µg/kg for ages 18-65 y or 40 µg/kg for ≥65 y). Two minutes later, propofol 2 mg/kg IV is administered. Upon loss of consciousness (MOAA/S ≤ 1), rocuronium 0.6 mg/kg IV is given. Direct laryngoscopic tracheal intubation is performed after full muscle relaxation. Blood pressure and heart rate are recorded at baseline, 2 min post-oliceridine, immediately pre-intubation, and for 3 min post-intubation. A "positive" hemodynamic response is defined as ≥ 20% increase in MAP or HR, HR ≥ 120 bpm, or SBP ≥ 180 mmHg. Subsequent oliceridine doses are adjusted ± 3 µg/kg based on the prior patient's response until seven response crossovers are observed, allowing estimation of ED₅₀ and ED₉₅.

Intervention Type: DRUG

Other Intervention Names

TRV130

Eligibility Criteria

Inclusion Criteria

• Elective surgery requiring general anesthesia with tracheal intubation
• Age ≥ 18 years
• American Society of Anesthesiologists (ASA) physical status I-III
• BMI<25

Exclusion Criteria

• At rest in the operating room, systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 110 mmHg or heart rate ≥ 110 bpm
• Preoperative long-term use of analgesic or sedative medications
• Pregnancy, breastfeeding, known or planned pregnancy
• Known allergy or hypersensitivity to oliceridine or any study medication components
• History of psychiatric illness or inability to communicate effectively

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shiyou Wei

OTHER

Sponsor Role: lead

Responsible Party

Shiyou Wei

Department of Anesthesiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Shiyou Wei, PhD

Role: STUDY_CHAIR

Shanghai Pulmonary Hospital, Shanghai, China

Locations

Tianmen First People's Hospital

Tianmen, Hubei, China

Countries

China

Other Identifiers

20250250

Identifier Type: -

Identifier Source: org_study_id