Effective Dose and Safety of Esketamine During Ultrasound-guided Hepatic Tumor Thermal Ablation

NCT07034950 | Active Not Recruiting Phase 1

• 1 other identifier: XMFHIIT-2025SL091
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

Effective pain management during percutaneous thermal ablation of liver tumors outside the operating room remains a significant challenge. While hepatic hilar nerve block (HHNB) provides partial analgesia, its incomplete efficacy often requires opioid supplementation, potentially increasing perioperative risks. Esketamine, an N-methyl-D-aspartate receptor antagonist, exhibits unique dual analgesic-sedative properties that may address this therapeutic gap, thus obviating the necessity for opioids. This prospective dose-finding study aimed to establish the median effective dose (ED50) and 95% effective dose (ED95) of esketamine for opioid-free analgesia during ultrasound-guided thermal ablation of liver tumors under HHNB. Afterwards, the investigators will conduct an RCT study to evaluate the safety of the dose of esketamine ED95 through the incidence of respiratory depression.

Conditions

Hepatic Neoplasm; Hepatic Cancer

Keywords

hepatic hilar nerve block; Ultrasound-guided; Thermal Ablation; Esketamine; Pain

Outcome Measures

Primary Outcomes (2)

• thermal ablation-induced somatic responses to pain

  Positive: Body movement or complaint of pain. Negative: No body movement or no reported pain. This scale will be administered during the surgery at the first stage of the research.

  Day 1 (During the surgery at the first stage of the research)

• Incidence of respiratory depression

  By comparing with the control group, evaluate the safety of ED95 of esketamine by the incidence of respiratory depression at T2-T5 of the second stage of the research. The primary outcome is the incidence of respiratory depression, which is defined as SpO2 \<90% or EtCO2 \>55 mmHg. T2: 60 seconds after esketamine injection; T3: 5 minutes after HHNB; T4: During thermal ablation of liver tumors; and T5: In the PACU.

  Day 1 (T2-T5 of the second stage of the research)

Secondary Outcomes (14)

• HR

  Day 1 (T1-T5 of the first and second stages of the research)

• MAP

  Day 1 (T1-T5 of the first and second stages of the research)

• RR

  Day 1 (T1-T5 of the first and second stages of the research)

• SPO2

  Day 1 (T1-T5 of the first and second stages of the research)

• EtCO2

  Day 1 (T2-T5 of the first and second stages of the research)

Study Arms (2)

Determine the ED50 and ED95 of esketamine by Dixon's up-and-down method

EXPERIMENTAL

Using Dixon's up-and-down sequential method, esketamine will be titrated intravenously from an initial 0.3 mg∙kg-1 dose with 0.02 mg∙kg-1 adjustments based on intraprocedural responses to pain (positive: purposeful somatic movement or the complaint of pain; negative: no movement or no complaint of pain). All patients will receive standardized premedication with HHNB. The titration sequence will continue until six crossover inflection points are observed.

Drug: Intravenous esketamine using Dixon's up-and-down sequential method

Evaluate the safety of the dose of esketamine ED95 by the incidence of respiratory depression

ACTIVE COMPARATOR

The intervention group will be injected with the dose of esketamine ED95; the control group will be injected with fentanyl 1 μg∙kg-1. The study at this stage will evaluate the safety of the dose of esketamine ED95 through the incidence of respiratory depression.

Drug: Intravenous the dose of esketamine ED95; Drug: Intravenous fentanyl 1 μg∙kg-1

Interventions

Intravenous esketamine using Dixon's up-and-down sequential method DRUG

Using Dixon's up-and-down sequential method, esketamine will be titrated intravenously from an initial 0.3 mg∙kg-1 dose with 0.02 mg∙kg-1 adjustments based on intraprocedural responses to pain (Positive: purposeful somatic movement or the complaint of pain; Negative: no movement or no complaint of pain). The titration sequence will continue until six crossover inflection points are observed.

Also known as: Ultrasound-guided hepatic hilar nerve block (HHNB), Standardized premedication (midazolam 0.03 mg∙kg-1), Local anaesthesia using 10 ml of 1% lidocaine

Determine the ED50 and ED95 of esketamine by Dixon's up-and-down method

Intravenous the dose of esketamine ED95 DRUG

The intervention group will be injected with the dose of esketamine ED95.

Also known as: Ultrasound-guided hepatic hilar nerve block (HHNB), Standardized premedication (midazolam 0.03 mg∙kg-1), Local anaesthesia using 10 ml of 1% lidocaine

Evaluate the safety of the dose of esketamine ED95 by the incidence of respiratory depression

Intravenous fentanyl 1 μg∙kg-1 DRUG

The control group will be injected with fentanyl 1 μg∙kg-1.

Also known as: Ultrasound-guided hepatic hilar nerve block (HHNB), Standardized premedication (midazolam 0.03 mg∙kg-1), Local anaesthesia using 10 ml of 1% lidocaine

Evaluate the safety of the dose of esketamine ED95 by the incidence of respiratory depression

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 - 80 years;
• ASA physical status Ⅰ or Ⅲ;
• Body mass index (BMI) 18 - 28 kg∙m-2;
• Scheduled for elective ultrasound-guided thermal ablation of solitary liver tumors under HHNB.

You may not qualify if:

• (i) Pharmacological contraindications:
• Known hypersensitivity to study medications (esketamine, midazolam);
• Opioid or benzodiazepine dependence;
• Using analgesics within the last 24 h preoperatively;
• Participation in other investigational drug trials within 90 days. (ii) Clinical comorbidities and surgery history:
• Multifocal hepatic lesions requiring concurrent ablation;
• Patients after liver transplantation;
• Active upper respiratory tract infection within 14 days;
• Severe cardiopulmonary diseases (New York Heart Association \[NYHA\] class Ⅲ-Ⅳ, FEV1/FVC \< 70%);
• Decompensated hepatic insufficiency (Child-Pugh C);
• Uncontrolled hypertension (≥180/110 mmHg), elevated intracranial/intraocular pressure, or hyperthyroidism;
• Major neuropsychiatric disorders (epilepsy, schizophrenia, major depressive disorder, cognitive impairment).
• (iii) Procedural Risk Factors:
• Anticipated difficult airway (Mallampati Ⅲ-Ⅳ, thyromental distance \< 6 cm) or anatomical airway obstruction;
• Inadequate preoperative fasting (solid intake \< 8 hours, clear fluids \< 2 hours).

Sponsors & Collaborators

• The First Affiliated Hospital of Xiamen University: lead

Study Sites (1)

Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, China

Xiamen, Fujian, 361000, China

Location

MeSH Terms

Conditions

Liver Neoplasms; Pain

Interventions

Lidocaine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Lijuan Yan

  Department of Anesthesiology, The First Affiliated Hospital of Xiamen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific Research Secretary of the Anesthesiology Department

Model Details: This research will be divided into two stages. (i) In Phase one, a prospective dose discovery study using the Dixon sequential method will be conducted, aiming to determine the median effective dose (ED50) and 95% effective dose (ED95) of esketamine during ultrasound-guided hepatic tumor thermal ablation under hilar nerve block (HHNB). The sample size is approximately 27. (ii) The investigators will conduct a single-center, randomized, double-blind controlled trial in Phase Two to evaluate the safety of the esketamine ED95 dose under the monitoring anesthesia care program based on the incidence of respiratory depression. The intervention group will be injected with the dose of esketamine ED95; the control group will be injected with fentanyl 1 μg∙kg-1. Both groups of patients will receive the same sedation regimen. The sample size is approximately 52.

Study Record Dates

• First Submitted: May 29, 2025
• First Posted: June 24, 2025
• Study Start: June 29, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: September 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)