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ElderlyPhase 4NCT07523334

Impact of Esketamine on Delayed Neurocognitive Recovery in Older Patients

A Phase 4 study testing Esketamine 1, Esketamine 2 and Esketamine 3 in people with Elderly and Noncardiac Surgery, run by Peking University First Hospital at 2 sites in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

Esketamine is frequently used during the perioperative period for supplemental analgesia. Small sample size trials showed that subanesthetic dose esketamine may decrease postoperative neurocognitive complications. However, conflicting results exist and optimal dose of esketamine remains to be determined. Read more about this study

Who is it for?
Ages 65 to 90 yearsHealthy volunteers can take part
What is being tested?
Esketamine 1, Esketamine 2 and Esketamine 3
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
120 participants
Where
2 sitesChina
Study dates
Apr 2026to Dec 2026
Phase
Phase 4
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 65 to 90 years
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • Aged >=65 but <= 90 years;
  • Scheduled to undergo non-cardiac surgery with an expected duration of >= 2 hours under general anesthesia;
  • Requiring patient-controlled intravenous analgesia (PCIA) after surgery.

Who cannot join

  • Unable to communicate preoperatively due to visual or auditory impairment, language barrier, or severe dementia;
  • Comorbid with schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis;
  • Traumatic brain injury or neurosurgery;
  • Severe hepatic dysfunction (Child-Pugh Class C), severe renal dysfunction (receiving dialysis preoperatively), or American Society of Anesthesiologists physical status classification >= Ⅳ;
  • Expected admission to the Intensive Care Unit with endotracheal intubation after surgery;
  • Anaphylaxis to esketamine;
  • Participation in other clinical studies, or any other conditions that are considered unsuitable to be involved in the study.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Dong-Xin Wang, MD, PhD contact

+86 13910731903

wangdongxin@hotmail.com

Jia-Hui Ma, PhD contact

mjh@bjmu.edu.cn

China2 sites

  • Peking University First Hospital

    Beijing, Beijing Municipality, 100034

    Jia-Hui Ma, PhD, mjh@bjmu.edu.cn

  • Tianjin Medical University General Hospital

    Tanjing, Tianjing, 300052

    Yi-Ze Li, MD, liyizelisa@126.com

Other trials in China

About this study

Official title: Impact of Esketamine on Delayed Neurocognitive Recovery in Older Patients Undergoing Non-cardiac Surgery: a Two-center, Dose-exploring Pilot Trial

Esketamine is frequently used during the perioperative period for supplemental analgesia. Small sample size trials showed that subanesthetic dose esketamine may decrease postoperative neurocognitive complications. However, conflicting results exist and optimal dose of esketamine remains to be determined. This dose-exploring pilot trial is designed to evaluate the safety and efficacy of three different perioperative esketamine dosing regimens in older patients undergoing major non-cardiac surgery. The primary purpose is to explore the optimal dosing strategy that produce maximal neurocognitive benefits with minimal adverse neuropsychiatric symptoms.

Read the detailed description

Postoperative neurocognitive complications including delirium and delayed neurocognitive recovery are common in older patients after major surgery and associated with worse early and long-term outcomes. Risk factors of neurocognitive complications are multiple. Predisposing factors include older age, low education, and cognitive decline. Precipitating factors include major surgery, high dose opioids, severe pain, and sleep disturbances. The underlying mechanisms are not totally clear but may include surgery-related stress response and inflammation.

Ketamine is a noncompetitive N-Methyl-D-aspartic acid (NMDA) receptor antagonist and has been used as an anesthetic and analgesic for decades. Esketamine is the S-enantiomer of ketamine and has an analgesic potent of approximately 2 times of that of ketamine. Available studies showed that subanesthetic dose ketamine/esketamine may reduce delirium and/or delayed neurocognitive recovery. However, conflicting results exist. Furthermore, even subanesthetic dose ketamine/esketamine may produce neuropsychiatric symptoms which are harmful for neurocognitive recovery.

This dose-exploring pilot trial is designed to evaluate the safety and efficacy of three different perioperative esketamine dosing regimens in older patients undergoing major non-cardiac surgery. The primary purpose is to explore the optimal dosing strategy that produce maximal neurocognitive benefits with minimal adverse neuropsychiatric symptoms.

Being tested
Esketamine 1, Esketamine 2, Esketamine 3, Normal saline
Keywords
Older patients, Noncardiac surgery, Delayed neurocognitive recovery, Postoperative delirium, Esketamine
Medical subject headings
Emergence Delirium

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Esketamine 1Drug

    Also called Esketamine dose 1

    During anesthesia, a loading dose esketamine (0.5 mg/ml) 0.4 ml/kg will be infused over 30 minutes (0.1 mg/kg) after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h (0.05 mg/kg/h) until 1 hour before the expected end of surgery.

    After surgery, patient-controlled intravenous analgesia will be established with esketamine (0.25 mg/ml) and sufentanil (1 ug/ml), programmed to deliver 2-ml bolus (0.5 mg esketamine) with a 8-10-minute lock-out time and a 1-ml/h (0.25 mg/h esketamine) background infusion, and used for up to 48 hours.

  • Esketamine 2Drug

    Also called Esketamine dose 2

    During anesthesia, a loading dose esketamine (1.0 mg/ml) 0.4 ml/kg will be infused over 30 minutes (0.2 mg/kg) after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h (0.1 mg/kg/h) until 1 hour before the expected end of surgery.

    After surgery, patient-controlled intravenous analgesia will be established with esketamine (0.5 mg/ml) and sufentanil (1 ug/ml), programmed to deliver 2-ml bolus (1 mg esketamine) with a 8-10-minute lock-out time and a 1-ml/h (0.5 mg/h esketamine) background infusion, and used for up to 48 hours.

  • Esketamine 3Drug

    Also called Esketamine dose 3

    During anesthesia, a loading dose esketamine (1.5 mg/ml) 0.4 ml/kg will be infused over 30 minutes (0.3 mg/kg) after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h (0.15 mg/kg/h) until 1 hour before the expected end of surgery.

    After surgery, patient-controlled intravenous analgesia will be established with esketamine (0.75 mg/ml) and sufentanil (1 ug/ml), programmed to deliver 2-ml bolus (1.5 mg esketamine) with a 8-10-minute lock-out time and a 1-ml/h (0.75 mg/h esketamine) background infusion, and used for up to 48 hours.

  • Normal salineDrug

    Also called Placebo

    During anesthesia, a loading dose placebo (normal saline) 0.4 ml/kg will be infused over 30 minutes after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h until 1 hour before the expected end of surgery.

    After surgery, patient-controlled intravenous analgesia will be established with sufentanil (1 ug/ml), programmed to deliver 2-ml bolus with a 8-10-minute lock-out time and a 1-ml/h background infusion, and used for up to 48 hours.

Study groups in NCT07523334
Study groupRoleWhat they receive
Esketamine dose 1ExperimentalDuring anesthesia, a loading dose esketamine (0.5 mg/ml) 0.4 ml/kg will be infused over 30 minutes (0.1 mg/kg) after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h (0.05 mg/kg/h) until 1 hour before the expected end of surgery. After surgery, patient-controlled intravenous analgesia will be established with esketamine (0.25 mg/ml) and sufentanil (1 ug/ml), programmed to deliver 2-ml bolus (0.5 mg esketamine) with a 8-10-minute lock-out time and a 1-ml/h (0.25 mg/h esketamine) background infusion, and used for up to 48 hours.
Receives: Drug: Esketamine 1
Esketamine dose 2ExperimentalDuring anesthesia, a loading dose esketamine (1 mg/ml) 0.4 ml/kg will be infused over 30 minutes (0.2 mg/kg) after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h (0.1 mg/kg/h) until 1 hour before the expected end of surgery. After surgery, patient-controlled intravenous analgesia will be established with esketamine (0.5 mg/ml) and sufentanil (1 ug/ml), programmed to deliver 2-ml bolus (1 mg esketamine) with a 8-10-minute lock-out time and a 1-ml/h (0.5 mg/h esketamine) background infusion, and used for up to 48 hours.
Receives: Drug: Esketamine 2
Esketamine dose 3ExperimentalDuring anesthesia, a loading dose esketamine (1.5 mg/ml) 0.4 ml/kg will be infused over 30 minutes (0.3 mg/kg) after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h (0.15 mg/kg/h) until 1 hour before the expected end of surgery. After surgery, patient-controlled intravenous analgesia will be established with esketamine (0.75 mg/ml) and sufentanil (1 ug/ml), programmed to deliver 2-ml bolus (1.5 mg esketamine) with a 8-10-minute lock-out time and a 1-ml/h (0.75 mg/h esketamine) background infusion, and used for up to 48 hours.
Receives: Drug: Esketamine 3
PlaceboPlacebo comparatorDuring anesthesia, a loading dose placebo (normal saline) 0.4 ml/kg will be infused over 30 minutes after anesthesia induction, followed by a continuous infusion at 0.1 ml/kg/h until 1 hour before the expected end of surgery. After surgery, patient-controlled intravenous analgesia will be established with sufentanil (1 ug/ml), programmed to deliver 2-ml bolus with a 8-10-minute lock-out time and a 1-ml/h background infusion, and used for up to 48 hours.
Receives: Drug: Normal saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dissociative symptoms

    Dissociative symptoms will be assessed at 30 minutes after extubation and then twice daily (8:00-10:00, 18:00-20:00) during the first 4 days after surgery, using the 6-item Clinician Administered Dissociative State Scale (CADSS-6; scores range frrom 0 to 24 with higher scores indicating more severe dissociative symptoms; a score >=3 indicates presence of dissociative symptoms).

    Measured: Up to 4 days after surgery

Secondary outcomes (3)

  1. Incidence of emergence delirium

    Emergence delirium will be assessed at 30 minutes after extubation, during stay in the postanesthesia care unit, using the Confusion Assessment Methods for the Intensive Care Unit (CAM-ICU).

    Measured: At 30 minutes after extubation

  2. Incidence of postoperative delirium

    Postoperative delirium will be assessed twice daily (8:00-10:00, 18:00-20:00) during the first 4 days after surgery, using the 3-Minute Diagnostic Interview for the Confusion Assessment Method (3D-CAM) for non-intubated patients or the Confusion Assessment Methods for the Intensive Care Unit (CAM-ICU) for intubated patients.

    Measured: Up to 4 days after surgery

  3. Incidence of delayed neurocognitive recovery

    Cognitive function will be assessed with the Montreal Cognitive Assessment (MoCA; scores range from 0 to 30, with higher scores indicating better function) at baseline and on the 5th day/before hospital discharge after surgery. Delayed neurocognitive recovery is defined as |Z| score of MoCA decline >=1.96. Z score = (MoCA change of patients - MoCA change of normal control)/standard deviation of MoCA change of normal control.

    Measured: Up to 5 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Apr 2026
  2. Study startApr 2026 (estimated)
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

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 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07523334
Sponsor's protocol ID
2026-0166
Status last verified
Apr 2026
First submitted
4 Apr 2026
Last updated
14 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Brodier EA, Cibelli M. Postoperative cognitive dysfunction in clinical practice. BJA Educ. 2021 Feb;21(2):75-82. doi: 10.1016/j.bjae.2020.10.004. Epub 2020 Dec 24. No abstract available.

    PubMed 33889433

  • Johnson T, Monk T, Rasmussen LS, Abildstrom H, Houx P, Korttila K, Kuipers HM, Hanning CD, Siersma VD, Kristensen D, Canet J, Ibanaz MT, Moller JT; ISPOCD2 Investigators. Postoperative cognitive dysfunction in middle-aged patients. Anesthesiology. 2002 Jun;96(6):1351-7. doi: 10.1097/00000542-200206000-00014.

    PubMed 12170047

  • Zhang ZR, Li YZ, Wu XQ, Chen WJ, Xu J, Zhao WH, Gong XY. Postoperative cognitive dysfunction in elderly postcardiac surgery patients: progress in rehabilitation application research. Front Rehabil Sci. 2024 Dec 17;5:1525813. doi: 10.3389/fresc.2024.1525813. eCollection 2024.

    PubMed 39741908

  • Liu Y, Fu H, Wang T. Neuroinflammation in perioperative neurocognitive disorders: From bench to the bedside. CNS Neurosci Ther. 2022 Apr;28(4):484-496. doi: 10.1111/cns.13794. Epub 2022 Jan 6.

    PubMed 34990087

  • Li YL, Huang HF, Le Y. Risk factors and predictive value of perioperative neurocognitive disorders in elderly patients with gastrointestinal tumors. BMC Anesthesiol. 2021 Jul 19;21(1):193. doi: 10.1186/s12871-021-01405-7.

    PubMed 34281529

  • Charipova K, Urits I, Viswanath O, Urman RD. Preoperative assessment and optimization of cognitive dysfunction and frailty in the ambulatory surgical patient. Curr Opin Anaesthesiol. 2020 Dec;33(6):732-739. doi: 10.1097/ACO.0000000000000901.

    PubMed 32769745

  • Amado LA, Perrie H, Scribante J, Ben-Israel KA. Preoperative cognitive dysfunction in older elective noncardiac surgical patients in South Africa. Br J Anaesth. 2020 Sep;125(3):275-281. doi: 10.1016/j.bja.2020.04.072. Epub 2020 Jun 10.

    PubMed 32532428

  • Mahanna-Gabrielli E, Schenning KJ, Eriksson LI, Browndyke JN, Wright CB, Culley DJ, Evered L, Scott DA, Wang NY, Brown CH 4th, Oh E, Purdon P, Inouye S, Berger M, Whittington RA, Price CC, Deiner S. State of the clinical science of perioperative brain health: report from the American Society of Anesthesiologists Brain Health Initiative Summit 2018. Br J Anaesth. 2019 Oct;123(4):464-478. doi: 10.1016/j.bja.2019.07.004. Epub 2019 Aug 19.

    PubMed 31439308

  • Berger M, Schenning KJ, Brown CH 4th, Deiner SG, Whittington RA, Eckenhoff RG, Angst MS, Avramescu S, Bekker A, Brzezinski M, Crosby G, Culley DJ, Eckenhoff M, Eriksson LI, Evered L, Ibinson J, Kline RP, Kofke A, Ma D, Mathew JP, Maze M, Orser BA, Price CC, Scott DA, Silbert B, Su D, Terrando N, Wang DS, Wei H, Xie Z, Zuo Z; Perioperative Neurotoxicity Working Group. Best Practices for Postoperative Brain Health: Recommendations From the Fifth International Perioperative Neurotoxicity Working Group. Anesth Analg. 2018 Dec;127(6):1406-1413. doi: 10.1213/ANE.0000000000003841.

    PubMed 30303868

  • Krzych LJ, Pluta MP, Putowski Z, Czok M. Investigating Association between Intraoperative Hypotension and Postoperative Neurocognitive Disorders in Non-Cardiac Surgery: A Comprehensive Review. J Clin Med. 2020 Sep 30;9(10):3183. doi: 10.3390/jcm9103183.

    PubMed 33008109

  • Wang T, Huang X, Sun S, Wang Y, Han L, Zhang T, Zhang T, Chen X. Recent Advances in the Mechanisms of Postoperative Neurocognitive Dysfunction: A Narrative Review. Biomedicines. 2025 Jan 7;13(1):115. doi: 10.3390/biomedicines13010115.

    PubMed 39857699

  • Fleischmann R, Leroy S. Perioperative Management and Its Impact on Neurocognitive Disorders in the Postoperative Scenario [M]//MARTIN C R, PREEDY V R, PATEL V B, et al. Handbook of the Biology and Pathology of Mental Disorders. Cham; Springer International Publishing. 2025: 1-28

  • Vaughan CW, Ingram SL, Connor MA, Christie MJ. How opioids inhibit GABA-mediated neurotransmission. Nature. 1997 Dec 11;390(6660):611-4. doi: 10.1038/37610.

    PubMed 9403690

  • Cao B, Xu Q, Shi Y, Zhao R, Li H, Zheng J, Liu F, Wan Y, Wei B. Pathology of pain and its implications for therapeutic interventions. Signal Transduct Target Ther. 2024 Jun 8;9(1):155. doi: 10.1038/s41392-024-01845-w.

    PubMed 38851750

  • Matveychuk D, Thomas RK, Swainson J, Khullar A, MacKay MA, Baker GB, Dursun SM. Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers. Ther Adv Psychopharmacol. 2020 May 11;10:2045125320916657. doi: 10.1177/2045125320916657. eCollection 2020.

    PubMed 32440333

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Esketamine 1, Esketamine 2 and Esketamine 3 in people with Elderly and Noncardiac Surgery, run by Peking University First Hospital at 2 sites 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 3 inclusion and 7 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: opening soon, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 Dong-Xin Wang, MD, PhD (+86 13910731903, wangdongxin@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dissociative symptoms (time frame: Up to 4 days after surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07523334, which also lists 38 linked publications.

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 14 Apr 2026.

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