Older PatientsPhase 4NCT07576543
Long-term Follow-up of Dexmedetomidine-esketamine and tDCS for Neurocognitive Complications After Surgery
A Phase 4 study testing Dex-Esk and Active tDCS in people with Older Patients and Surgery, run by Peking University First Hospital at 6 sites in China.
Trial summary
Neurocognitive complications, mainly delirium and neurocognitive disorders, are common cerebral complications in older patients after surgery and associated with worse long-term outcomes. Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Older Patients, Surgery, Dexmedetomidine
- What is being tested?
- Dex-Esk and Active tDCS
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,996 participants
- Where
- 6 sitesChina
- Study dates
- Oct 2026to Dec 2031
- Phase
- Phase 4
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 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Aged 65 to 90 years;
- Preoperative Mini-Cognitive Assessment (Mini-Cog) score ≤ 2 points, indicating possible cognitive impairment ranging from mild to moderate;
- Scheduled to undergo elective non-cardiac, non-neurosurgical surgery under general anesthesia, with an expected surgical duration > 1 hour;
- Required patient-controlled intravenous analgesia (PCIA) after surgery.
Who cannot join
- Preoperative inability to communicate due to coma, severe dementia, endstage disease, or language impairment;
- History of schizophrenia, epilepsy, Parkinson's disease, brain trauma/surgery, or myasthenia gravis;
- Presence of metal implants in the intracranial or cervical region (such as cochlear implants, aneurysm clips, deep brain stimulation electrodes), or skin damage or severe skin disease on the head;
- Severe cardiac dysfunction (left ventricular ejection fraction < 30%), comorbid with sick sinus syndrome, severe bradycardia (heart rate < 50 bpm), or second-degree or higher atrioventricular block, or implantation of a cardiac pacemaker;
- Uncontrolled hyperthyroidism or pheochromocytoma;
- Severe liver dysfunction (Child-Pugh class C), severe renal dysfunction (requiring dialysis), or ASA classification ≥ IV;
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- Allergy to dexmedetomidine or esketamine;
- Participation in other clinical studies within the past 3 months;
- Emergency surgery or organ transplant surgery;
- Other conditions that are deemed unsuitable for study participation.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
China6 sites
Peking University First Hospital
Beijing, Beijing Municipality, 100034
Dong-Xin Wang, MD, PhD, +86 10 83572784, wangdongxin@hotmail.com
Zhen-Zhen Xu, MD, 86 10 83572460, zjxvzhenzhen@126.com
Fujian Medical University Union Hospital
Fuzhou, Fujian, 362011
Dan-Feng Zhang, MD, mazui1234@163.com
First Affilited Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310006
Dian-San Su, MD, diansansu@yahoo.com
Second Affilited Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310009
Min Yan, MD, zryanmin@zju.edu.cn
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036
Tao Luo, MD, 496855048@qq.com
Xijing Hospital, Air Force Medical University
Xi'an, Shaanxi, 710032
Zhi-Hong Lu, MD, deerlu23@163.com
About this study
Official title: Long-term Follow-up of Perioperative Dexmedetomidine-esketamine Combination and Transcranial Direct Current Stimulation for Prevention of Neurocognitive Complications in Older Patients After Non-cardiac Surgery
Neurocognitive complications, mainly delirium and neurocognitive disorders, are common cerebral complications in older patients after surgery and associated with worse long-term outcomes. An ongoing 2×2 factorial trial conducted by the investigators plan to test the effects of perioperative dexmedetomidine-esketamine combination and transcranial direct current stimulation (tDCS) on postoperative neurocognitive complications in older patients. This long-term follow-up of the ongoing trial aims to investigate the effects of perioperative dexmedetomidine-esketamine combination and tDCS on long-term outcomes in older patients after noncardiac surgery.
Read the detailed description
Neurocognitive complications, mainly delirium and neurocognitive disorders, are common cerebral complications in older patients after surgery. Occurrence of neurocognitive complications is associated with prolonge hospital stay and increased in-hospital death. Furthermore, occurrence of neurocognitive complications is associated with adverse long-term outcomes, including cognitive decline, poor quality of life, and reduced long-term survival.
Dexmedetomidine is a highly selective alpha 2 adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. Available evidence showed that perioperative dexmedetomidine decreased early postoperative neurocognitive complications in older patients, possibly by improving analgesia and sleep quality and relieving surgery-related inflammation. However, routine dose dexmedetomidine increases bradycardia and hypotension which are potentially harmful to older patients.
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 twice as potent as racemic ketamine. Recent studies found that subanesthetic dose of esketamine is effective in improving analgesia and sleep quality and relieving surgery-related stress response. However, even subanesthetic ketamine or esketamine increases neuropsychiatric side effects.
In clinical practice, dexmedetomidine-esketamine combination has been used for premedication in children and postoperative analgesia in adults and showed additive or synergistic effects. An ongoing trial conducted by the investigators plan to test the hypothesis that perioperative use of dexmedetomidine-esketamine combination may prevent postoperative neurocognitive complications in older patients. It is reasonable to hypothesize that perioperative dexmedetomdine-esketamine might also have favorable effects on long-term outcomes.
Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique and increasingly used for treatment of various neurological diseases. Studies in the perioperative settings showed that perioperative use of tDCS improved sleep quality and reduced delirium occurrence early after surgery. The ongoing trial coducted by the investigators plan to test the hypothesis that perioperative use of tDCS may reduce postoperative neurocognitive complications in older patients. Perioperative tDCS might also have favorable effects on long-term outcomes.
This long-term follow-up of the ongoing 2×2 factorial trial aims to investigate the effects of perioperative dexmedetomidine-esketamine combination and tDCS on long-term outcomes in older patients after noncardiac surgery.
- Conditions
- Older Patients, Surgery, Dexmedetomidine, Esketamine, Transcranial Direct Current Stimulation, Cognitive Function
- Being tested
- Dex-Esk, Placebo, Active tDCS, Sham tDCS
- Keywords
- Older patients, Surgery, Dexmedetomidine, Esketamine, Transcranial direct current stimulation, Cognitive function, Survival
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dex-EskDrug
Also called Dexmedetomidine-esketamine combination
Dexmedetomidine-esketamine combination (1 μg/mL dexmedetomidine and 0.5 mg/mL esketamine) will be administered after anesthesia induction, firstly as a loading dose at a rate of [0.4 x body weight (kg)] mL/h for 30 minutes (0.2 μg/kg dexmedetomidine and 0.1 mg/kg esketamine), followed by a maintenance infusion at a rate of [0.1 x body weight (kg)] mL/h (0.1 μg/kg/h dexmedetomidine and 0.05 mg/kg/h esketamine) until one hour before expected end surgery.
Postoperative patient-controlled analgesia will be established with a 100 mL mixture (containing 1.0 μg/mL sufentanil, 1.0 μg/mL dexmedetomidine, and 0.25 mg/mL esketamine in normal saline), programmed to deliver 2-mL boluses with an 8-minute lockout interval and an 1-mL/h background infusion, and provided for 48 hours (at least 24 hours).
PlaceboDrug
Also called Normal saline
Placebo (normal saline) will be administered after anesthesia induction, firstly as a loading dose at a rate of [0.4 x body weight (kg)] mL/h for 30 minutes, followed by a maintenance infusion at a rate of [0.1 x body weight (kg)] mL/h until one hour before expected end surgery.
Postoperative patient-controlled analgesia will be established with a 100 mL mixture (containing 1.0 μg/mL sufentanil in normal saline), programmed to deliver 2-mL boluses with an 8-minute lockout interval and an 1-mL/h background infusion, and provided for 48 hours (at least 24 hours).
Active tDCSDevice
Also called Active transcranial direct current stimulation
Active transcranial direct current stimulation (tDCS) will be administered using a battery-powered stimulator. The anode will be positioned over the left dorsolateral prefrontal cortex (DLPFC, F3) and the cathode over the right supraorbital region (Fp2). The stimulation intensity will be set at 2.0 mA, featuring a 30-second linear ramp-up at the beginning and a 30-second ramp-down at the end of each session.
Each participant will receive a total of three 20-minute sessions of active tDCS. The first session will be provided at 40 minutes after extubation in the post-anesthesia care unit. Two other sessions will be provided on postoperative days 1 and 2 (between 10:00 and 12:00 am).
Sham tDCSDevice
Also called Sham transcranial direct current stimulation
Sham transcranial direct current stimulation (tDCS) will be administered using a battery-powered stimulator. The anode will be positioned over the left dorsolateral prefrontal cortex (DLPFC, F3) and the cathode over the right supraorbital region (Fp2). To ensure blinding, the device will deliver a initial 30-second ramp-up to 2.0 mA followed immediately by a 30-second ramp-down to 0 mA. The device remains "ON" for the remaining 19 minutes with no effective current output, mimicking the peripheral scalp sensation without delivering cortical modulation.
Each participant will receive a total of three 20-minute sessions of sham tDCS. The first session will be provided at 40 minutes after extubation in the post-anesthesia care unit. Two other sessions will be provided on postoperative days 1 and 2 (between 10:00 and 12:00 am).
| Study group | Role | What they receive |
|---|---|---|
| Dex-Esk + active tDCS | Experimental | Participants will receive dexmedetomidine-esketamine (Dex-Esk) combination and active transcranial direct current stimulation (tDCS). Receives: Drug: Dex-Esk; Device: Active tDCS |
| Dex-Esk + sham tDCS | Experimental | Participants will receive dexmedetomidine-esketamine (Dex-Esk) combination and sham (placebo) transcranial direct current stimulation (tDCS). Receives: Drug: Dex-Esk; Device: Sham tDCS |
| Placebo + active tDCS | Experimental | Participants will receive placebo (normal saline) and active transcranial direct current stimulation (tDCS). Receives: Drug: Placebo; Device: Active tDCS |
| Placebo + sham tDCS | Placebo comparator | Participants will receive placebo (normal saline) and sham (placebo) transcranial direct current stimulation (tDCS). Receives: Drug: Placebo; Device: Sham tDCS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of postoperative neurocognitive disorders (pNCD) at 3 months
Cognitive function will be assessed at baseline using the Montreal Cognitive Assessment (MoCA; scores range from 0 to 30, with higher scores indicating better cognitive function), and at 3 months after surgery using the Telephone MoCA (T-MoCA; scores range from 0 to 22, with higher scores indicating better cognitive function).
Postoperative neurocognitive disorders (pNCD) is defined as a decrease in T-MoCA score from baseline of ≥1 SD (standardized deviation).
Measured: At 3 months after surgery
Secondary outcomes (1)
Event-free survival
Time interval from index surgery to cancer recurrence/metastasis/progression, new-onset cancer, new-onset serious illness (requiring hospitalization), or all-cause death, whichever comes first.
Measured: Up to 1 year after surgery of the last enrolled patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2026
- Study startOct 2026 (estimated)
- Primary completionDec 2030 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (84)Papers the sponsor has linked to this study.
- Other trials for Older PatientsStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,996 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University First Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Peking University Shenzhen Hospital, Second Affiliated Hospital, Zhejiang University, School of Medicine, Fujian Medical University Union Hospital, The First Affiliated Hospital of Air Force Medicial University, First Affiliated Hospital of Zhejiang University
- Responsible party
- Principal investigator, Dong-Xin Wang, Peking University First Hospital
- Investigators
- Dong-Xin Wang, MD, PhD, Principal investigator, Peking University First Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07576543
- Sponsor's protocol ID
- 2026-1219-LT
- Other IDs
- 82293644
- Status last verified
- Oct 2026
- First submitted
- 3 May 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PubMed 19097774Tao M, Yang J, Liu R, Zhang S, Han Y, Li C, Wei Q, Chen D, Fang J, Zhang H, Wang Y, Liu H, Cao JL. Efficacy of transcranial direct current stimulation for improving postoperative quality of recovery in elderly patients undergoing lower limb major arthroplasty: a randomized controlled substudy. Front Neurol. 2024 Jan 24;15:1327558. doi: 10.3389/fneur.2024.1327558. eCollection 2024.
PubMed 38327619Rodrigues NB, McIntyre RS, Lipsitz O, Lee Y, Cha DS, Shekotikhina M, Vinberg M, Gill H, Subramaniapillai M, Kratiuk K, Lin K, Ho R, Mansur RB, Rosenblat JD. A simplified 6-Item clinician administered dissociative symptom scale (CADSS-6) for monitoring dissociative effects of sub-anesthetic ketamine infusions. J Affect Disord. 2021 Mar 1;282:160-164. doi: 10.1016/j.jad.2020.12.119. Epub 2020 Dec 29.
PubMed 33418362Shinall MC Jr, Arya S, Youk A, Varley P, Shah R, Massarweh NN, Shireman PK, Johanning JM, Brown AJ, Christie NA, Crist L, Curtin CM, Drolet BC, Dhupar R, Griffin J, Ibinson JW, Johnson JT, Kinney S, LaGrange C, Langerman A, Loyd GE, Mady LJ, Mott MP, Patri M, Siebler JC, Stimson CJ, Thorell WE, Vincent SA, Hall DE. Association of Preoperative Patient Frailty and Operative Stress With Postoperative Mortality. JAMA Surg. 2020 Jan 1;155(1):e194620. doi: 10.1001/jamasurg.2019.4620. Epub 2020 Jan 15.
PubMed 31721994Zisapel N, Nir T. Determination of the minimal clinically significant difference on a patient visual analog sleep quality scale. J Sleep Res. 2003 Dec;12(4):291-8. doi: 10.1046/j.0962-1105.2003.00365.x.
PubMed 14633240Martin S, Chandran A, Zografos L, Zlateva G. Evaluation of the impact of fibromyalgia on patients' sleep and the content validity of two sleep scales. Health Qual Life Outcomes. 2009 Jul 10;7:64. doi: 10.1186/1477-7525-7-64.
PubMed 19591683Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.
PubMed 2748771Wang W, Bian Q, Zhao Y, Li X, Wang W, Du J, Zhang G, Zhou Q, Zhao M. Reliability and validity of the Chinese version of the Patient Health Questionnaire (PHQ-9) in the general population. Gen Hosp Psychiatry. 2014 Sep-Oct;36(5):539-44. doi: 10.1016/j.genhosppsych.2014.05.021. Epub 2014 Jun 6.
PubMed 25023953Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969 Autumn;9(3):179-86. No abstract available.
PubMed 5349366Lai Y, Zhao M, Jiang C, Du X, Wang Z, Zhang J, Bai Y, Xu B, Zhang W, Tang R, Sang C, Long D, Dong J, Ma C. Validation of T-MoCA in the Screening of Mild Cognitive Impairment in Chinese Patients With Atrial Fibrillation. Front Cardiovasc Med. 2022 Jun 22;9:896846. doi: 10.3389/fcvm.2022.896846. eCollection 2022.
PubMed 35811734Wong A, Nyenhuis D, Black SE, Law LS, Lo ES, Kwan PW, Au L, Chan AY, Wong LK, Nasreddine Z, Mok V. Montreal Cognitive Assessment 5-minute protocol is a brief, valid, reliable, and feasible cognitive screen for telephone administration. Stroke. 2015 Apr;46(4):1059-64. doi: 10.1161/STROKEAHA.114.007253. Epub 2015 Feb 19.
PubMed 25700290Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.
PubMed 15817019Creavin ST, Wisniewski S, Noel-Storr AH, Trevelyan CM, Hampton T, Rayment D, Thom VM, Nash KJ, Elhamoui H, Milligan R, Patel AS, Tsivos DV, Wing T, Phillips E, Kellman SM, Shackleton HL, Singleton GF, Neale BE, Watton ME, Cullum S. Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations. Cochrane Database Syst Rev. 2016 Jan 13;2016(1):CD011145. doi: 10.1002/14651858.CD011145.pub2.
PubMed 26760674Kunicki ZJ, Ngo LH, Marcantonio ER, Tommet D, Feng Y, Fong TG, Schmitt EM, Travison TG, Jones RN, Inouye SK. Six-Year Cognitive Trajectory in Older Adults Following Major Surgery and Delirium. JAMA Intern Med. 2023 May 1;183(5):442-450. doi: 10.1001/jamainternmed.2023.0144.
PubMed 36939716Li C, Tao M, Chen D, Wei Q, Xiong X, Zhao W, Tan W, Yang J, Han Y, Zhang H, Zhang S, Liu H, Cao JL. Transcranial Direct Current Stimulation for Anxiety During Laparoscopic Colorectal Cancer Surgery: A Randomized Clinical Trial. JAMA Netw Open. 2024 Apr 1;7(4):e246589. doi: 10.1001/jamanetworkopen.2024.6589.
PubMed 38635271