Study on the Effective Dose and Safety of Esketamine in Hysteroscopic Surgery Under Monitored Anesthesia Care

July 21, 2025 updated by: Lijuan Yan, The First Affiliated Hospital of Xiamen University
Cervical dilation-induced somatic responses remain a critical challenge in ambulatory hysteroscopic surgery. Esketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exhibits unique analgesic and sedative properties that may enhance perioperative somatic response inhibition. However, the effective dose of esketamine under dexmedetomidine-remifentanil based monitored anesthesia care (MAC) during ambulatory hysteroscopic surgery remains to be determined. This prospective dose-finding study aimed to establish the median effective dose (ED50) and 95% effective dose (ED95) of esketamine for cervical response suppression. Afterwards, the investigators will conduct an RCT study to evaluate the safety of the dose of esketamine ED95 through the incidence of respiratory depression.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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 in inhibiting cervical response. Esketamine will be initiated by intravenous infusion at 0.3 mg∙kg-1, followed by somatic response based on cervical dilation (positive: any exercise; negative: no movement). Dose adjustment will be carried out, with a dose fluctuation step of 0.02 mg∙kg-1 up and down. All patients will receive a standardized anesthesia regimen, including continuous infusion of remifentanil at a dose of 5 μg∙kg∙h-1, combined with dexmedetomidine (infusion at a loading dose of 0.6 μg∙kg-1 for 10 minutes, followed by maintenance infusion at 0.4 μg∙kg-1∙h-1). The test will continue until six cross-pairings are obtained. Probabilistic regression analysis will be used to calculate the ED50 and ED95 of esketamine with a 95% confidence interval.

(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 remifentanil 1μg∙kg-1. Both groups of patients will receive the same sedation regimen, namely remifentanil will be continuously pumped at a rate of 5μg∙kg∙h-1 combined with dexmedetomidine (pumped at a loading dose of 0.6 μg∙kg-1 for 10 minutes, followed by maintenance pumping at 0.4 μg∙kg-1∙h-1). Intravenous injection of 100 mg of flurbiprofen axetil for auxiliary analgesia. Intravenous injection of 4 mg of ondansetron to prevent nausea and vomiting.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
95

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Fujian
      • Xiamen, Fujian, China, 361000
        • Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, China

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged 18 - 55 years;
  • ASA physical status Ⅰ or Ⅱ;
  • Body mass index (BMI) 18 - 28 kg∙m-2;
  • Scheduled for elective diagnostic/therapeutic hysteroscopy.

Exclusion Criteria:

(i) Pharmacological contraindications:

  • Known hypersensitivity to study medications (esketamine, remifentanil, dexmedetomidine);
  • Opioid or benzodiazepine medications dependence;
  • Analgesic/psychotropic medication use within 48 hours preoperatively;
  • Participation in any other drug clinical trial within the preceding three months.

(ii) Comorbidities:

  • Significant cardiopulmonary dysfunction (NYHA III-IV, FEV₁/FVC <70%);
  • Hepatic impairment (Child-Pugh B/C);
  • Uncontrolled hypertension, intracranial hypertension, intraocular hypertension or hyperthyroidism;
  • Neurological/psychiatric conditions (epilepsy, schizophrenia, depression);
  • Active gastroesophageal reflux disease (GERD-Q score ≥8). (iii) Airway/Perioperative Risks:
  • Anticipated difficult airway (Mallampati III-IV, thyromental distance <6 cm) or airway stenosis;
  • Non-fasted status (solids <8h, clear fluids <2h preoperatively).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Determine the ED50 and ED95 of esketamine by Dixon's up-and-down method
According to Dixon's up-and-down sequential design, esketamine will be initiated at 0.3 mg∙kg-1 intravenously, followed by dose adjustments (0.02 mg∙kg-1 increments/decrements) based on somatic responses to cervical dilation (positive: any movement; negative: no movement). The tests will continue until six crossover pairs are achieved.
Drug: Determine the ED50 and ED95 of esketamine
According to Dixon's up-and-down sequential design, esketamine will be initiated at 0.3 mg∙kg-1 intravenously, followed by dose adjustments (0.02 mg∙kg-1 increments/decrements) based on somatic responses to cervical dilation (positive: any movement; negative: no movement). The tests will continued until six crossover pairs are achieved.
Other Names:
  • Remifentanil will be continuously pumped at a rate of 5μg∙kg∙h-1 combined with dexmedetomidine (a loading dose of 0.6 μg∙kg-1 for 10 minutes, followed by maintenance dose of 0.4 μg∙kg-1∙h-1).
Active Comparator: Evaluate the safety of the dose of esketamine ED95 by the incidence of respiratory depression
The intervention group will be injected with the dose of esketamine ED95; the control group will be injected with remifentanil 1μg∙kg-1. Both groups of patients will receive the same Monitoring Anesthesia Care (MAC) regimen, namely, remifentanil will be continuously pumped at a rate of 5μg∙kg∙h-1 combined with dexmedetomidine (a loading dose of 0.6 μg∙kg-1 for 10 minutes, followed by maintenance dose of 0.4 μg∙kg-1∙h-1). Intravenous injection of 100 mg of flurbiprofen axetil for auxiliary analgesia. Intravenous injection of 4 mg of ondansetron to prevent nausea and vomiting. 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
The intervention group will be injected with the dose of esketamine ED95.
Other Names:
  • Remifentanil will be continuously pumped at a rate of 5μg∙kg∙h-1 combined with dexmedetomidine (a loading dose of 0.6 μg∙kg-1 for 10 minutes, followed by maintenance dose of 0.4 μg∙kg-1∙h-1).
Drug: Intravenous remifentanil 1μg∙kg-1
The control group will be injected with remifentanil 1μg∙kg-1.
Other Names:
  • Remifentanil will be continuously pumped at a rate of 5μg∙kg∙h-1 combined with dexmedetomidine (a loading dose of 0.6 μg∙kg-1 for 10 minutes, followed by maintenance dose of 0.4 μg∙kg-1∙h-1).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cervical dilation-induced somatic responses
Time Frame: Day 1 (During the surgery at the first stage of the research)
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
Time Frame: Day 1 (T2-T6 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.

By comparing with the control group, evaluate the safety of ED95 of esketamine by the incidence of respiratory depression at T2-T6 of the second stage of the research.

T2: 60 seconds after esketamine injection; T3: During vaginal disinfection; T4: During cervical dilation; T5: During intrauterine operations; T6: In the PACU.
Day 1 (T2-T6 of the second stage of the research)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
HR
Time Frame: Day 1 (T1-T6 of the first and second stages of the research)
HR: heart rate. T1: Prior to anesthesia (10 minutes after positioning); T2: 60 seconds after esketamine injection; T3: During vaginal disinfection; T4: During cervical dilation; T5: During intrauterine operations; T6: In the PACU.
Day 1 (T1-T6 of the first and second stages of the research)
MAP
Time Frame: Day 1 (T1-T6 of the first and second stages of the research)
MAP: Mean Arterial Pressure. T1: Prior to anesthesia (10 minutes after positioning); T2: 60 seconds after esketamine injection; T3: During vaginal disinfection; T4: During cervical dilation; T5: During intrauterine operations; T6: In the PACU.
Day 1 (T1-T6 of the first and second stages of the research)
RR
Time Frame: Day 1 (T1-T6 of the first and second stages of the research)
RR: respiratory rate. T1: Prior to anesthesia (10 minutes after positioning); T2: 60 seconds after esketamine injection; T3: During vaginal disinfection; T4: During cervical dilation; T5: During intrauterine operations; T6: In the PACU.
Day 1 (T1-T6 of the first and second stages of the research)
SPO2
Time Frame: Day 1 (T1-T6 of the first and second stages of the research)
SPO2: peripheral oxygen saturation. T1: Prior to anesthesia (10 minutes after positioning); T2: 60 seconds after esketamine injection; T3: During vaginal disinfection; T4: During cervical dilation; T5: During intrauterine operations; T6: In the PACU.
Day 1 (T1-T6 of the first and second stages of the research)
EtCO2
Time Frame: Day 1 (T2-T6 of the first and second stages of the research)
EtCO2: End-expiratory carbon dioxide. SPO2: peripheral oxygen saturation. T2: 60 seconds after esketamine injection; T3: During vaginal disinfection; T4: During cervical dilation; T5: During intrauterine operations; T6: In the PACU.
Day 1 (T2-T6 of the first and second stages of the research)
Adverse events
Time Frame: Day 1 (T2-T9 of the first and second stages of the research)

Adverse events will encompass a range of systems, including the cardiovascular system (eg. high/low blood pressure and sinus tachycardia/bradycardia), as well as symptoms such as nausea, vomiting, dizziness, and mental symptoms.

T2: 60 seconds after esketamine injection; T3: During vaginal disinfection; T4: During cervical dilation; T5: During intrauterine operations; T6: In the PACU. T7 to T9: 2, 6, and 24 hours after the procedure.
Day 1 (T2-T9 of the first and second stages of the research)
NRS
Time Frame: Day 1 (T7-T9 of the first and second stages of the research)

The Numeric Rating Scale (NRS) will be utilized to assess postoperative pain, with a range of 0 representing no pain and 10 representing severe pain. This scale will be administered at 2, 6, and 24 hours following the procedure.

T7 to T9: 2, 6, and 24 hours after the procedure.
Day 1 (T7-T9 of the first and second stages of the research)
The need for remedial analgesia
Time Frame: Day 1 (T7-T9 of the first and second stages of the research)

The consumption of remedial analgesia will be the total consumption of acetaminophen documented at 2, 6, and 24 hours after the procedure.

T7 to T9: 2, 6, and 24 hours after the procedure.
Day 1 (T7-T9 of the first and second stages of the research)
Induction duration
Time Frame: Day 1 of the first and second stages of the research
Induction duration is defined as the period from the start of anaesthetic drug injection to the commencement of the surgical procedure at the first and second stages of the research.
Day 1 of the first and second stages of the research
Duration of awakening
Time Frame: Day 1 of the first and second stages of the research
Duration of awakening is defined as the period from the conclusion of the surgical procedure to the moment of eye-opening.
Day 1 of the first and second stages of the research
Success rate of anesthesia
Time Frame: Day 1 (T2-T5 of the second stage of the research)

Anesthesia success will be defined as inadequate analgesia requiring ≤3 rescue doses of remifentanil within 10 min throughout the procedure. The success rate of anesthesia will be calculated by dividing the number of successful anesthesia cases by the total number of cases.

T2: 60 seconds after esketamine injection; T3: During vaginal disinfection; T4: During cervical dilation; T5: During intrauterine operations.
Day 1 (T2-T5 of the second stage of the research)
The satisfaction of gynecologists
Time Frame: Day 1 of the second stage of the research
The satisfaction score of gynecologists will be collected postoperatively on Day 1, using a scale ranging from 0 to 10, with 0 representing dissatisfaction and 10 representing very satisfied.
Day 1 of the second stage of the research
The satisfaction of patients
Time Frame: Day 2 of the second stage of the research
The satisfaction of patients will be collected postoperatively on Day 2, using a scale ranging from 0 to 10, with 0 representing dissatisfaction and 10 representing very satisfied.
Day 2 of the second stage of the research
PACU time
Time Frame: Day 1 of the first and second stages of the research
The time from patient admission to the PACU until the fulfillment of the criteria for PACU discharge.
Day 1 of the first and second stages of the research
Discharge time
Time Frame: Day 1 of the first and second stages of the research
The interval between patient admission to the operating room and the fulfillment of the criteria for hospital discharge.
Day 1 of the first and second stages of the research

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The First Affiliated Hospital of Xiamen University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Lijuan Yan, Department of Anesthesiology, The First Affiliated Hospital of Xiamen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 26, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 29, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 24, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 24, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 21, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • XMFHIIT-2025SL092

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Intrauterine Synechiae

Clinical Trials on Determine the ED50 and ED95 of esketamine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings