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The Effects of Subanesthetic S-ketamine on Postoperative Delirium and Cognitive Function in the Elderly Undergoing Non-cardiac Thoracic Surgery (SKED)

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ClinicalTrials.gov Identifier: NCT05242692
Recruitment Status : Recruiting
First Posted : February 16, 2022
Last Update Posted : March 9, 2022
Sponsor:
Information provided by (Responsible Party):
Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Tracking Information
First Submitted Date  ICMJE December 23, 2021
First Posted Date  ICMJE February 16, 2022
Last Update Posted Date March 9, 2022
Actual Study Start Date  ICMJE February 17, 2022
Estimated Primary Completion Date December 16, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 15, 2022)		 Number of Patients With Post-operative Delirium in 4 Days After Surgery [ Time Frame: Within 4 days after surgery ]
3-minute Diagnostic Confusion Assessment Method (3D-CAM)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2022)
  • Severity of Delirium [ Time Frame: Within 4 days after surgery ]
    Confusion Assessment Method- Severity (CAM-S, Mild-to-moderate delirium will be defined as a CAM-S score of 3 to 5, while severe delirium will be defined as a CAM-S score of 6 to 7)
  • Duration of postoperative delirium [ Time Frame: Within 4 days after surgery ]
    Positive days of postoperative delirium
Original Secondary Outcome Measures  ICMJE
 (submitted: February 15, 2022)
  • Severity of Delirium [ Time Frame: Within 4 days after surgery ]
    CAM- Severity (Mild-to-moderate delirium will be defined as a CAM-S score of 3 to 5, while severe delirium will be defined as a CAM-S score of 6 to 7)
  • Duration of postoperative delirium [ Time Frame: Within 4 days after surgery ]
    Positive days of postoperative delirium
Current Other Pre-specified Outcome Measures
 (submitted: February 22, 2022)
  • Emergency delirium [ Time Frame: From 30 minutes after the arrival in the post anesthesia care unit (PACU) until the time-point of PACU discharge, assessed up to 2 hours ]
    Richard Agitation-Sedation Scale (RASS) (RASS score ≥ 1 indicates emergency delirium, the higher scores mean a worse outcome.)
  • Pain severity [ Time Frame: Within 2 days after surgery ]
    Numeric rating scale (NRS)0 = [no pain], 0 < NRS < 4 [mild pain], 4 ≤ NRS < 7 [moderate pain], 7 ≤ NRS <10 [severe pain], NRS = 10 [worst pain imaginable]
  • Quality of sleep [ Time Frame: Within 4 days after surgery ]
    Numeric rating scale(0 = best-quality sleep, 10 = worst-quality sleep)
  • Cognitive function [ Time Frame: On postoperative day 30 ]
    Telephone interview for cognitive status-40 (TICS-40); A score below 21 will be defined as mild cognitive impairment, the higher scores mean a worse outcome.
  • Cognitive function [ Time Frame: On postoperative day 60 ]
    Telephone interview for cognitive status-40 (TICS-40); A score below 21 will be defined as mild cognitive impairment, the higher scores mean a worse outcome.
  • Concentration of plasma acetylcholine (ACh) [ Time Frame: Within 5 minutes before induction ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma acetylcholine (ACh) [ Time Frame: Within 5 minutes after the end of skin closure ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma acetylcholine (ACh) [ Time Frame: On postoperative day 4 ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma brain deprived neurotrophic factor (BDNF) [ Time Frame: Within 5 minutes before induction ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma brain deprived neurotrophic factor (BDNF) [ Time Frame: Within 5 minutes after the end of skin closure ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma brain deprived neurotrophic factor (BDNF) [ Time Frame: On postoperative day 4 ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma tumor necrosis factor (TNF) [ Time Frame: Within 5 minutes before induction ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma tumor necrosis factor (TNF) [ Time Frame: Within 5 minutes after the end of skin closure ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma tumor necrosis factor (TNF) [ Time Frame: On postoperative day 4 ]
    Enzyme-linked immunosorbent assay (ELISA) method
Original Other Pre-specified Outcome Measures
 (submitted: February 15, 2022)
  • Emergency delirium [ Time Frame: From 30 minutes after the arrival in the post anesthesia care unit (PACU) until the time-point of PACU discharge, assessed up to 2 hours ]
    Richard Agitation-Sedation Scale (RASS) (RASS score ≥ 1 indicates emergency delirium)
  • Pain severity [ Time Frame: Within 2 days after surgery ]
    Numeric rating scale (NRS)0 = [no pain], 0 < NRS < 4 [mild pain], 4 ≤ NRS < 7 [moderate pain], 7 ≤ NRS <10 [severe pain], NRS = 10 [worst pain imaginable]
  • Quality of sleep [ Time Frame: Within 4 days after surgery ]
    Numeric rating scale(0 = best-quality sleep, 10 = worst-quality sleep)
  • Cognitive function [ Time Frame: On postoperative day 30 ]
    Telephone interview for cognitive status-40 (TICS-40); A score below 21 will be defined as mild cognitive impairment
  • Cognitive function [ Time Frame: On postoperative day 60 ]
    Telephone interview for cognitive status-40 (TICS-40); A score below 21 will be defined as mild cognitive impairment
  • Concentration of plasma acetylcholine (ACh) [ Time Frame: Within 5 minutes before induction ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma acetylcholine (ACh) [ Time Frame: Within 5 minutes after the end of skin closure ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma acetylcholine (ACh) [ Time Frame: On postoperative day 4 ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma brain deprived neurotrophic factor (BDNF) [ Time Frame: Within 5 minutes before induction ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma brain deprived neurotrophic factor (BDNF) [ Time Frame: Within 5 minutes after the end of skin closure ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma brain deprived neurotrophic factor (BDNF) [ Time Frame: On postoperative day 4 ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma tumor necrosis factor (TNF) [ Time Frame: Within 5 minutes before induction ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma tumor necrosis factor (TNF) [ Time Frame: Within 5 minutes after the end of skin closure ]
    Enzyme-linked immunosorbent assay (ELISA) method
  • Concentration of plasma tumor necrosis factor (TNF) [ Time Frame: On postoperative day 4 ]
    Enzyme-linked immunosorbent assay (ELISA) method
 
Descriptive Information
Brief Title  ICMJE The Effects of Subanesthetic S-ketamine on Postoperative Delirium and Cognitive Function in the Elderly Undergoing Non-cardiac Thoracic Surgery
Official Title  ICMJE The Effects of Subanesthetic S-ketamine on Postoperative Delirium and Cognitive Function in the Elderly Undergoing Non-cardiac Thoracic Surgery: a Protocol for Randomized, Double-blinded, placebo-and Positive-controlled, Non-inferiority Trial
Brief Summary Postoperative delirium (POD) is a common and distressing complication after thoracic surgery. S-ketamine has neuroprotective properties as a dissociative anesthetic. Emerging literature has indicated that S-ketamine can reduce cognitive impairment in depressed patients. However, the role of S-ketamine in preventing postoperative delirium is still unknown. Therefore, this study aims to evaluate the effect of intraoperatively prophylactic S-ketamine compared to dexmedetomidine on the incidence of postoperative delirium in elderly patients undergoing non-cardiac thoracic surgery.
Detailed Description Postoperative delirium (POD) is a common and distressing complication after thoracic surgery. S-ketamine has neuroprotective properties as a dissociative anesthetic. Emerging literature has indicated that S-ketamine can reduce cognitive impairment in depressed patients. However, the role of S-ketamine in preventing postoperative delirium is still unknown. Therefore, this study aims to evaluate the effect of intraoperatively prophylactic S-ketamine compared to dexmedetomidine on the incidence of postoperative delirium in elderly patients undergoing non-cardiac thoracic surgery. This will be a randomized, double-blinded, placebo-and positive-controlled, non-inferiority trial that enrolls patients aged 60 or over undergoing thoracic surgery. The primary outcome will be the incidence of postoperative delirium within 4 days after surgery and assessed using a 3-minute Diagnostic Confusion Assessment Method (3D-CAM) twice a day. The main secondary outcomes will be the severity and duration of postoperative delirium. Other prespecified secondary outcomes will be the incidence of emergency delirium, postoperative pain, quality of sleep, cognitive function, and the plasm concentration of acetylcholine, brain-derived neurotrophic factor, and tumor necrosis factor.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
The labeled "Study medication" syringes (50ml) in identical appearance, and the infusion regimen formulated by the pharmacist based on the randomization, will be distributed to the attending anesthesiologists responsible for anesthetic management as soon as the research team informs the central pharmacy about the patient heading for surgery. To avoid anesthesiologists' speculation about the randomized assignment, the study drugs will be infused at a similar rate. The anesthesiologists, the patients, the investigators responsible for follow-up, and the statisticians are all masked to randomized allocations until the final statistical analyses are completed. The blindness will be unmasked by the primary investigator in a medical emergency including deterioration of patient's condition intraoperatively or adverse events postoperatively.
Primary Purpose: Prevention
Condition  ICMJE
  • Postoperative Delirium
  • Elderly Patients
Intervention  ICMJE
  • Drug: S-ketamine
    Loading dose: 0.25mg/kg in 10 minutes Maintenance dose: 0.1mg/kg/h
  • Drug: Dexmedetomidine
    Loading dose: 0.4 ug/kg in 10 minutes Maintenance dose: 0.2 ug/kg/h
  • Drug: Normal saline
    Refer to either S-ketamine or Dexmedetomidine
Study Arms  ICMJE
  • Experimental: S-ketamine
    S-ketamine (50 mg, 2 ml) is diluted to 50 ml (1 mg/ml) with 48 ml normal saline;
    Intervention: Drug: S-ketamine
  • Active Comparator: Dexmedetomidine
    Dexmedetomidine (200 ug, 2 ml) is diluted to 100 ml (2 ug/ml) with 98 ml normal saline;
    Intervention: Drug: Dexmedetomidine
  • Placebo Comparator: Normal saline
    Control group only contains 50 ml normal saline in light of blindness
    Intervention: Drug: Normal saline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 15, 2022)		 780
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2024
Estimated Primary Completion Date December 16, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged 60 years or over
  • Both genders
  • American anesthesiologist association (ASA) physical status classificationⅠ-Ⅲ
  • Diagnosed with lung, esophagus, or mediastinum disorders
  • Undergoing open or video-assisted thoracic surgery including lobectomy, segmentectomy, pneumonectomy, esophagectomy, or resection of mediastinal tumor
  • General anesthesia with one-lung ventilation (OLV) or bronchial blocker.
  • An expected operation duration of 2 hours or more.
  • Voluntarily participate in the trial and sign informed consent.

Exclusion Criteria:

  • History of psychiatric disease or severe depression
  • History of glaucoma or hyperthyroidism
  • History of severe hepatic (Child-Pugh grade C) or renal (requirement for renal replacement therapy) disorder.
  • Body mass index (BMI) greater 35 kg/m2
  • Dementia history or baseline Mini-Mental State Examination (MMSE) score less than 23
  • Severe audio-visual impairments, or inability to speak Mandarin or Cantonese precluding communication
  • Sinus bradycardia (heart rate < 50 beats per minutes, bpm), sick sinus or Wolff- Parkinson-White syndromes, or Ⅱ degree atrioventricular block and over
  • Poorly controlled hypertension (resting systolic blood pressure over 180 mm Hg, or resting diastolic blood pressure over 100 mm Hg)
  • Allergic to dexmedetomidine, S-ketamine or any of their formulation ingredients;
  • Taking sedatives, antidepressants or glucocorticoids
  • Alcohol or drug abuser
  • Life expectancy of less than 2 months due to extensive tumor metastasis.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: WEI WEI, MD +8618520698366 1575041594@qq.com
Contact: Yonghua Yao, MD +8613711568864 726832646@qq.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05242692
Other Study ID Numbers  ICMJE ATHGuangzhou
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Yihua Li, PhD Cancer hospital and institute of Guangzhou medical university
PRS Account Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP