Determination of the 90% Effective Dose (ED90) of Tegileridine Fumarate for Inhibiting Hemodynamic Stress Response Induced by Tracheal Intubation During General Anesthesia: A Biased Coin Up-and-Down Sequential Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 108
- Locations
- 1
- Primary Endpoint
- ED90 to suppress hemodynamic response of tracheal intubation
Study Overview
Brief Summary
General anesthesia tracheal intubation causes sympathetic activation and hemodynamic stress response, which increases perioperative cardiovascular risk, especially in elderly subjects. Tegileridine fumarate is a novel μ-opioid receptor G protein-biased agonist. However, the optimal dose of tegileridine to suppress intubation-induced hemodynamic fluctuations during anesthesia induction remains unclear.
This is an open-label, single-center, age-stratified biased coin up-and-down sequential trial. Subjects undergoing elective surgery requiring tracheal intubation will be divided into young adult group (18-64 years) and elderly group (≥65 years). The primary objective is to determine the ED90 of intravenous tegileridine for inhibiting hemodynamic response to tracheal intubation using centered isotonic regression. Secondary outcomes include investigational-drug adverse events, serial hemodynamic parameters. This study will provide evidence for rational dosing of tegileridine in clinical anesthesia induction.
Detailed Description
Tracheal intubation under general anesthesia stimulates the airway and triggers transient hypertension and tachycardia due to sympathetic excitation. Excessive hemodynamic fluctuations may trigger myocardial ischemia, arrhythmia and other adverse cardiovascular events. Traditional opioids simultaneously activate G-protein and β-arrestin pathways, often accompanied by obvious respiratory depression. As a newly marketed biased μ-opioid agonist, tegileridine exerts analgesic effects with reduced β-arrestin related side effects. Up to now, few studies have explored the effective dose of tegileridine for blunting intubation stress.
We conduct a single-center, open-label sequential dose-finding trial stratified by age. Eligible subjects are ASA I-III patients scheduled for elective surgery with tracheal intubation. Subjects receive intravenous tegileridine before anesthetic induction. The dose is adjusted according to biased coin up-and-down rule based on whether a positive cardiovascular response occurs after intubation. We adopt centered isotonic regression to calculate the 90% effective dose (ED90). Blood pressure, heart rate, investigational-drug adverse reactions will be recorded.The findings of this trial will establish a dosing reference of tegileridine for anesthesia induction and facilitate safer perioperative management.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •American Society of Anesthesiologists (ASA) physical status I-III
- •Aged ≥18 ears old
- •Scheduled for elective surgery requiring general anesthesia with tracheal intubation
Exclusion Criteria
- •Resting Systolic Blood Pressure ≥ 160 mmHg, Diastolic Blood Pressure ≥ 110 mmHg, or heart rate ≥ 110 beats/min on admission to operation room
- •Continuous opioid medication use for more than 2 weeks within 6 months before the procedure
- •Known hypersensitivity or allergic reaction to tegileridine, propofol or any excipients of the two drugs
- •Diagnosed psychiatric disorders or inability to communicate and cooperate with study assessment
- •Anticipated difficult airway
Arms & Interventions
Intervention Arm
All enrolled subjects receive intravenous tegileridine before anesthesia induction. The dose of tegileridine is adjusted sequentially for each subsequent subject following the biased coin up-and-down rule. General anesthesia and tracheal intubation are performed according to standardized protocol.
Intervention: Tegileridine (Drug)
Outcomes
Primary Outcomes
ED90 to suppress hemodynamic response of tracheal intubation
Time Frame: Within 3 minutes after tracheal intubation
Successful suppression of hemodynamic response is defined as a maximum increase in hemodynamic variables ≤20% from baseline within 3 minutes after tracheal intubation. Centered isotonic regression will be used to calculate the ED₉₀ of tegileridine.
Secondary Outcomes
- Number of subjects with cough during the study drug (tegileridine) administration and observation period.(From the start of tegileridine injection until 2 minutes after completion of injection.)
Investigators
Shiyou Wei
Attending Physician, Department of Anesthesiology
Shanghai Pulmonary Hospital, Shanghai, China