Knee OsteoarthritisNCT07736352
Exploration of Appropriate BIS Range and Propofol Effect-site Concentration During Total Intravenous Anesthesia With Concomitant Adjuvants.
A study testing Propofol + Remifentanil +Midazolam, Propofol + Remifentanil + Dexmedetomidine and Propofol + Remifentanil + Esketamine in people with Knee Osteoarthritis and Replacement, Knee, run by China-Japan Friendship Hospital at 1 site in China.
Trial summary
The goal of this clinical trial is to determine the appropriate Bispectral Index (BIS) range and propofol effect-site concentration required to maintain adequate anesthesia depth during total intravenous anesthesia (TIVA) combined with midazolam, dexmedetomidine, or esketamine in patients undergoing unilateral knee… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Knee Osteoarthritis, Replacement, Knee, Elective Surgical Patients
- What is being tested?
- Propofol + Remifentanil +Midazolam, Propofol + Remifentanil + Dexmedetomidine and Propofol + Remifentanil + Esketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 30 Jul 2026to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 65 years
- American Society of Anesthesiologists (ASA) physical status I or II
- Body Mass Index (BMI) 18 to 30 kg/m²
- Scheduled for elective unilateral total knee replacement surgery
- Willing to participate in the study and signed informed consent form, and able to comply with the intervention and assessment procedures
Who cannot join
- History of neurological disorders
- Cognitive dysfunction assessed by the Mini-Cog scale
- History of antipsychotic or sedative medication use in the past 4 weeks
- Poorly controlled or untreated hypertension
- Sinus bradycardia, cardiac conduction block, or severe heart failure
- Acute angle-closure glaucoma
Show all 9Show fewer
- Allergic to intravenous anesthetics
- Hearing impairment, could not cooperate in intervention and evaluation
- Contraindications to tourniquet use on the upper arm
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
China-Japan Friendship Hospital
Beijing
Ye Ma, +86 13552629329, maye_1316@163.com
About this study
Official title: A Prospective, Randomized Study to Determine the Appropriate Bispectral Index Range and Propofol Effect-Site Concentration During Total Intravenous Anesthesia Combined With Midazolam, Dexmedetomidine or Esketamine.
The goal of this clinical trial is to determine the appropriate Bispectral Index (BIS) range and propofol effect-site concentration required to maintain adequate anesthesia depth during total intravenous anesthesia (TIVA) combined with midazolam, dexmedetomidine, or esketamine in patients undergoing unilateral knee replacement surgery. The main questions it aims to answer are:
- What are the appropriate BIS range and propofol effect-site concentration for maintaining adequate anesthesia depth when combined with each of the three medications (midazolam, dexmedetomidine, or esketamine) during TIVA?
- How these combination regimens affect the quality of recovery and postoperative pain in patients？
Read more
Participants will:
- Receive one of four anesthesia regimens during surgery: propofol alone, propofol combined with midazolam, dexmedetomidine, or esketamine.
- Undergo a stepwise reduction of propofol effect-site concentration towards the end of surgery.
- Have their consciousness assessed using the isolated forearm technique, while BIS, EEG signals, and vital signs are continuously monitored throughout the procedure.
- Have their recovery quality and postoperative pain assessed after surgery.
- Conditions
- Knee Osteoarthritis, Replacement, Knee, Elective Surgical Patients, ASA Class I/II Patients
- Being tested
- Propofol + Remifentanil +Midazolam, Propofol + Remifentanil + Dexmedetomidine, Propofol + Remifentanil + Esketamine, Propofol + Remifentanil
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Propofol + Remifentanil +MidazolamDrug
Participants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. Midazolam (2 mg) will be administered intravenously.The propofol plasma-site concentration will be set to 1.8 μg/mL, then reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS > 60 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate.
Propofol + Remifentanil + DexmedetomidineDrug
Participants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. Dexmedetomidine 1 μg/kg infused over 10 minutes.The propofol plasma-site concentration will be set to 1.8 μg/mL, then reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS > 60 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate.
Propofol + Remifentanil + EsketamineDrug
Participants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. Esketamine (0.3 mg/kg) will be administered intravenously.The propofol plasma-site concentration will be set to 1.8 μg/mL, then reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS > 75 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate.
Propofol + RemifentanilDrug
Participants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. The propofol plasma-site concentration will be reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS > 60 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate.
| Study group | Role | What they receive |
|---|---|---|
| Propofol + Remifentanil | Sham comparator | Not described Receives: Drug: Propofol + Remifentanil |
| Propofol + Remifentanil + Midazolam | Experimental | Not described Receives: Drug: Propofol + Remifentanil +Midazolam |
| Propofol + Remifentanil + Dexmedetomidine | Experimental | Not described Receives: Drug: Propofol + Remifentanil + Dexmedetomidine |
| Propofol + Remifentanil + Esketamine | Experimental | Not described Receives: Drug: Propofol + Remifentanil + Esketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
BIS value
BIS value recorded at the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia.
Measured: From the start of the intra-operative stepwise reduction phase until the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia, assessed up to 30 minutes.
Propofol Effect-Site Concentration
Propofol effect-site concentration recorded at the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia.
Measured: From the start of the intra-operative stepwise reduction phase until the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia, assessed up to 30 minutes.
Secondary outcomes (6)
Modified Brice Questionnaire
The presence of intra-operative awareness with recall is assessed using the Modified Brice Questionnaire. The questionnaire explores the patient's memory of the peri-operative period through structured questions.
Measured: From PACU admission to 48 hours postoperatively. Assessed before PACU discharge, 24 hours and 48 hours postoperatively.
Time from Discontinuation of Anesthetics to Laryngeal Mask Airway Removal
From discontinuation of anesthetics to LMA removal. Successful removal is defined as the patient being awake, able to open mouth on command, and having return of protective reflexes, without signs of respiratory distress.
Measured: From discontinuation of anesthetics to LMA removal, assessed up to 60 minutes.
Time to Modified Aldrete Score of 10 in the Post Anesthesia Care Unit
Time from post anesthesia care unit (PACU) admission until the first attainment of a Modified Aldrete Score of 10. The Modified Aldrete Score assesses five domains: consciousness, activity, respiration, blood pressure, and oxygen saturation, each scored from 0 to 2, with a maximum total score of 10. A score of 10 indicates the patient has achieved optimal recovery in all five domains.
Measured: From PACU admission to Modified Aldrete Score of 10, assessed up to 60 minutes.
Adverse Events During Emergence from Anesthesia
Adverse events during the period from anesthetic discontinuation to PACU discharge are recorded.
Measured: From discontinuation of anesthetics to PACU discharge, assessed up to 2 hours.
Postoperative Pain Intensity Measured by Numeric Rating Scale
Pain intensity is assessed using the Numeric Rating Scale, an 11-point scale from 0 to 10, where 0 represents "no pain" and 10 represents "the worst imaginable pain". Patients are asked to rate their current pain intensity at each assessment time point. The Numeric Rating Scale is a widely used and validated measure for postoperative pain assessment.
Measured: From PACU admission to 48 hours postoperatively. Assessed at PACU admission, PACU discharge, 24 hours and 48 hours postoperatively.
Analgesic Consumption
Total amount of rescue analgesic medication administered to the patient from PACU admission to 48 hours postoperatively.
Measured: From PACU admission to 48 hours postoperatively. Recorded during PACU stay, 24 hours and 48 hours postoperatively.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2026
- Study start30 Jul 2026
- Primary completion31 Jan 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- More trials run by China-Japan Friendship HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- China-Japan Friendship Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ma Ye, China-Japan Friendship Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07736352
- Sponsor's protocol ID
- 2026-HX-39
- Status last verified
- Jul 2026
- First submitted
- 16 Jul 2026
- Last updated
- 28 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized Study to Determine the Appropriate Bispectral Index Range and Propofol Effect-Site Concentration During Total Intravenous Anesthesia Combined With Midazolam, Dexmedetomidine or Esketamine.
- ClinicalTrials.gov ID
- NCT07736352
- Acronym / sponsor ID
- 2026-HX-39
- Conditions
- Knee Osteoarthritis, Replacement, Knee, Elective Surgical Patients, ASA Class I/II Patients
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- China-Japan Friendship HospitalUniversity, hospital or other
- Study start
- 30 Jul 2026 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 30 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to determine the appropriate Bispectral Index (BIS) range and propofol effect-site concentration required to maintain adequate anesthesia depth during total intravenous anesthesia (TIVA) combined with midazolam, dexmedetomidine, or esketamine in patients undergoing unilateral knee replacement surgery. The main questions it aims to answer are:
- What are the appropriate BIS range and propofol effect-site concentration for maintaining adequate anesthesia depth when combined with each of the three medications (midazolam, dexmedetomidine, or esketamine) during TIVA?
- How these combination regimens affect the quality of recovery and postoperative pain in patients？
Participants will:
- Receive one of four anesthesia regimens during surgery: propofol alone, propofol combined with midazolam, dexmedetomidine, or esketamine.
- Undergo a stepwise reduction of propofol effect-site concentration towards the end of surgery.
- Have their consciousness assessed using the isolated forearm technique, while BIS, EEG signals, and vital signs are continuously monitored throughout the procedure.
- Have their recovery quality and postoperative pain assessed after surgery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Propofol + Remifentanil | Sham comparator | Drug: Propofol + Remifentanil |
| Propofol + Remifentanil + Midazolam | Experimental | Drug: Propofol + Remifentanil +Midazolam |
| Propofol + Remifentanil + Dexmedetomidine | Experimental | Drug: Propofol + Remifentanil + Dexmedetomidine |
| Propofol + Remifentanil + Esketamine | Experimental | Drug: Propofol + Remifentanil + Esketamine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 to 65 years
- American Society of Anesthesiologists (ASA) physical status I or II
- Body Mass Index (BMI) 18 to 30 kg/m²
- Scheduled for elective unilateral total knee replacement surgery
- Willing to participate in the study and signed informed consent form, and able to comply with the intervention and assessment procedures
Key exclusion criteria (9 listed)
- History of neurological disorders
- Cognitive dysfunction assessed by the Mini-Cog scale
- History of antipsychotic or sedative medication use in the past 4 weeks
- Poorly controlled or untreated hypertension
- Sinus bradycardia, cardiac conduction block, or severe heart failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Propofol + Remifentanil +MidazolamParticipants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. Midazolam (2 mg) will be administered intravenously.The propofol plasma-site concentration will be set to 1.8 μg/mL, then reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS > 60 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate. | Drug | Propofol + Remifentanil + Midazolam |
| Propofol + Remifentanil + DexmedetomidineParticipants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. Dexmedetomidine 1 μg/kg infused over 10 minutes.The propofol plasma-site concentration will be set to 1.8 μg/mL, then reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS > 60 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate. | Drug | Propofol + Remifentanil + Dexmedetomidine |
| Propofol + Remifentanil + EsketamineParticipants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. Esketamine (0.3 mg/kg) will be administered intravenously.The propofol plasma-site concentration will be set to 1.8 μg/mL, then reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS > 75 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate. | Drug | Propofol + Remifentanil + Esketamine |
| Propofol + RemifentanilParticipants in this arm will receive total intravenous anesthesia (TIVA) with propofol and remifentanil during the maintenance period. After placement of the knee prosthesis, the isolated forearm technique (IFT) will be initiated. Participants will wear headphones playing recorded standardized instructions. Rocuronium (0.3 mg/kg) will be administered via the non-dominant arm. The propofol plasma-site concentration will be reduced in stepwise decrements of 0.3 μg/mL, with each concentration maintained for 5 minutes, until any of the following endpoints is reached: (1) positive IFT response , (2) BIS > 60 sustained for 1 minute, (3) electroencephalogram signs of arousal, or (4) clinical judgment by the anesthesiologist that anesthesia depth is inadequate. | Drug | Propofol + Remifentanil |
Primary outcome
BIS value
Time frame: From the start of the intra-operative stepwise reduction phase until the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia, assessed up to 30 minutes.
BIS value recorded at the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia.
Propofol Effect-Site Concentration
Time frame: From the start of the intra-operative stepwise reduction phase until the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia, assessed up to 30 minutes.
Propofol effect-site concentration recorded at the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia.
6 secondary outcomes
Modified Brice Questionnaire
Time frame: From PACU admission to 48 hours postoperatively. Assessed before PACU discharge, 24 hours and 48 hours postoperatively.
Time from Discontinuation of Anesthetics to Laryngeal Mask Airway Removal
Time frame: From discontinuation of anesthetics to LMA removal, assessed up to 60 minutes.
Time to Modified Aldrete Score of 10 in the Post Anesthesia Care Unit
Time frame: From PACU admission to Modified Aldrete Score of 10, assessed up to 60 minutes.
Adverse Events During Emergence from Anesthesia
Time frame: From discontinuation of anesthetics to PACU discharge, assessed up to 2 hours.
Postoperative Pain Intensity Measured by Numeric Rating Scale
Time frame: From PACU admission to 48 hours postoperatively. Assessed at PACU admission, PACU discharge, 24 hours and 48 hours postoperatively.
Analgesic Consumption
Time frame: From PACU admission to 48 hours postoperatively. Recorded during PACU stay, 24 hours and 48 hours postoperatively.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Propofol + Remifentanil +Midazolam, Propofol + Remifentanil + Dexmedetomidine and Propofol + Remifentanil + Esketamine in people with Knee Osteoarthritis and Replacement, Knee, run by China-Japan Friendship Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact MA (+86-10-84205882, maye_1316@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BIS value (time frame: From the start of the intra-operative stepwise reduction phase until the first occurrence of IFT positivity or any predefined clinical sign of inadequate anesthesia, assessed up to 30 minutes.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026; AzTrials last refreshed its copy on 6 Nov 2026.