ED90 of Tegileridine for Suppressing Hemodynamic Response to Tracheal Intubation: A Biased Coin Up-and-Down Trial

Официальное название

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

Обзор

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 induction-related adverse events, serial hemodynamic parameters and sedation scale. This study will provide evidence for rational dosing of tegileridine in clinical anesthesia induction.

Подробное описание

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, induction adverse reactions and sedation scores will be recorded. All adverse events will be closely monitored throughout induction. The findings of this trial will establish a dosing reference of tegileridine for anesthesia induction and facilitate safer perioperative management.

Вмешательства

• Препарат Tegileridine
  Intravenous tegileridine administered prior to anesthesia induction. The initial dose and dose adjustment steps are predefined; individual dose will be modified by biased coin up-and-down sequential method to explore ED90 for inhibiting hemodynamic response to tracheal intubation.

Первичные конечные точки

• ED90 to suppress hemodynamic response of tracheal intubation [Срок оценки: Within 3 minutes after tracheal intubation]

Критерии участия

Критерии включения

• American Society of Anesthesiologists (ASA) physical status I-III
• Aged 18-90 years old
• Scheduled for elective surgery requiring general anesthesia with tracheal intubation
• No predicted difficult airway

Критерии исключения

• Resting Systolic Blood Pressure ≥ 160 mmHg, Diastolic Blood Pressure ≥ 110 mmHg, or heart rate ≥ 110 beats/min on admission to endoscopy 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shaoyang University Affiliated First Hospital — Shaoyang

Идентификаторы

NCT: NCT07749131 · shaoyang-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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