A Phase 1/2 interventional study of Determine the ED50 and ED95 of esketamine and Intravenous the dose of esketamine ED95 in Intrauterine Polyp and Intrauterine Synechiae, sponsored by The First Affiliated Hospital of Xiamen University. Active, not recruiting at 1 site in China. Open to female participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2025-07-24.
Sponsored by The First Affiliated Hospital of Xiamen University · Phase 1/2, Interventional, and Supportive care
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.
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.
49 studies on the registry are indexed under Gynatresia; 17 are open to participants now.
This study's planned enrollment of 95 is close to the median of 95 across 41 interventional studies indexed under Gynatresia.
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Exclusion Criteria:
(i) Pharmacological contraindications:
(ii) Comorbidities:
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
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 · Drug: Intravenous remifentanil 1μg∙kg-1
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.
Also known as: 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).
The intervention group will be injected with the dose of esketamine ED95.
Also known as: 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).
The control group will be injected with remifentanil 1μg∙kg-1.
Also known as: 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).
Cervical dilation-induced somatic responses
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.
Time frame: Day 1 (During the surgery at the first stage of the research)
Incidence of respiratory depression
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.
Time frame: Day 1 (T2-T6 of the second stage of the research)
HR
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.
Time frame: Day 1 (T1-T6 of the first and second stages of the research)
MAP
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.
Time frame: Day 1 (T1-T6 of the first and second stages of the research)
RR
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.
Time frame: Day 1 (T1-T6 of the first and second stages of the research)
SPO2
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.
Time frame: Day 1 (T1-T6 of the first and second stages of the research)
EtCO2
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.
Time frame: Day 1 (T2-T6 of the first and second stages of the research)
Adverse events
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.
Time frame: Day 1 (T2-T9 of the first and second stages of the research)
NRS
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.
Time frame: Day 1 (T7-T9 of the first and second stages of the research)
The need for remedial analgesia
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.
Time frame: Day 1 (T7-T9 of the first and second stages of the research)
Induction duration
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.
Time frame: Day 1 of the first and second stages of the research
Duration of awakening
Duration of awakening is defined as the period from the conclusion of the surgical procedure to the moment of eye-opening.
Time frame: Day 1 of the first and second stages of the research
PACU time
The time from patient admission to the PACU until the fulfillment of the criteria for PACU discharge.
Time frame: Day 1 of the first and second stages of the research
Discharge time
The interval between patient admission to the operating room and the fulfillment of the criteria for hospital discharge.
Time frame: Day 1 of the first and second stages of the research
Success rate of anesthesia
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.
Time frame: Day 1 (T2-T5 of the second stage of the research)
The satisfaction of gynecologists
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.
Time frame: Day 1 of the second stage of the research
The satisfaction of patients
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.
Time frame: Day 2 of the second stage of the research
Plan to share: No
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The First Affiliated Hospital of Xiamen University