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Safety and Efficacy Evaluation of S (+) - Ketamine in Adults

Primary Purpose

Postoperative Pain, Adults, Anesthesia

Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Conventional therapy + S (+)-Ketamine
Conventional therapy
Sponsored by
Chinese PLA General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postoperative Pain focused on measuring S-ketamine,Esketamine,S (+) - ketamine, Acute Pain, Depression, Anxiety, Delirium, Hyperalgesia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 1. Age ≥18 years old;
  • 2. Scheduled for elective digestive tract surgery, gynecological surgery, urological surgery, thoracic surgery, orthopedic limb surgery, orthopedic spine surgery or body surface surgery (thyroid surgery or breast surgery), head and neck surgery;
  • 3. ASA score Ⅰ～Ⅲ;
  • 4. The informed consent form was signed by the patients.

Exclusion Criteria:

  • 1. The expected length of hospital stay of the patient is less than 48h;
  • 2. Patients expected to be admitted to the ICU after surgery;
  • 3. Patients expected to return to the ward with tracheal catheter after surgery;
  • 4. Be allergic to S (+) - ketamine;
  • 5. Patients with severe disorder of consciousness or mental system diseases (schizophrenia, mania, bipolar disorder, psychosis, etc.) or cognitive dysfunction;
  • 6. Patients with a history of severe cardiovascular disease (congestive heart failure, severe angina attack, or unstable angina or myocardial infarction within 6 months);
  • 7. Patients during pregnancy or lactation;
  • 8. Patients with MMSE score <18 points;

  • 9. Patients with any of the following contraindications of S (+) - ketamine:

    1. Patients with risk of serious rise of blood pressure or intracranial pressure;
    2. Patients with high intraocular pressure (glaucoma) or penetrating ocular trauma;
    3. Patients with poorly controlled or untreated hypertension (Resting systolic blood pressure greater than 180 mmHg, or resting diastolic blood pressure greater than 100mmHg);
    4. Patients with untreated or undertreated hyperthyroidism.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    S (+)-Ketamine group

    Control group

    Arm Description

    Drug: Conventional therapy + S (+)-Ketamine In principle, there are no specific restrictions on the dosage, mode of administration, timing, and compatibility of S-ketamine hydrochloride injection,but the recommended dosage is given, which is lower than the dosage specified in the instructions. Recommended use and dosage of S (+)-Ketamine: Bolus intravenous injection before skin incision, the dose is 0.1~0.5 mg/kg; Bolus intravenous injection (dose 0.1~0.5 mg/kg) before skin incision +continuous intravenous infusion (dose of 0.1~0.25 mg/kg/h) during operation; Continuous intravenous infusion after surgery with a dose of 0.02~0.1 mg/kg/h for 24~48 h.

    Drug: Conventional therapy Receiving conventional therapy without S (+)-Ketamine hydrochloride injection. There is no restrictions in drugs, doses and incompatibility, the researchers can choose appropriate medication regimens based on clinical practice, but other NMDA receptor antagonists are not be allowed to use, such as dextromethorphan and amantadine.

    Outcomes

    Primary Outcome Measures

    The area under the broken line of NRS score
    The score of Numerical Rating Scale(NRS) is 0-10, the higher the score, the more severe the pain.
    Opioid consumption
    Total opioid consumption(conversion to equivalent morphine)

    Secondary Outcome Measures

    NRS pain scores
    The score of Numerical Rating Scale(NRS) is 0-10, the higher the score, the more severe the pain.
    Time of first rescue analgesia
    The time from the end of the operation to the first rescue analgesics after the operation. Rescue analgesia refers to the analgesia according to the patient's requirements in addition to routine postoperative analgesia.
    The incidence of rescue analgesia
    The incidence of rescue analgesia within 48h after surgery
    Recovery time
    The time from the end of the operation to recovery(can be awakened)
    The incidence of unexpected intraoperative events
    Unexpected events during operation include intraoperative cough, laryngeal spasm, body movement, tachycardia,decreased oxygen saturation, respiratory depression, bradycardia, hypertension and hypotension.
    The Patient Efficacy Questionnaire (IPOQ ) scores
    Patient Efficacy Questionnaire (IPOQ ) scale include 13 questions , each question's score is 0-10 or 0-100%, it involves postoperative pain, mood and quality of life. The higher the score, the more severe the pain symptoms.
    The incidence of adverse events after surgery
    The incidence of adverse events from the end of the operation to 48h after surgery. Including nausea, vomiting, increased secretions, dizziness, oversedation, infection,anesthetic awareness, nightmares, restlessness, pruritus, disorientation, delirium, respiratory depression, diplopia, diarrhea, intestinal obstruction, urinary retention, gastroesophageal reflux, constipation, chills, hallucinations, etc.
    Pharmacoeconomic indicators
    Calculating incremental cost-effectiveness ratio （ICER）based on cost-effectiveness analysis.
    Incidence of postoperative delirium
    The Chinese version of the 3D-CAM scale is used for the diagnosis of delirium, and the assessment will be carried out at 24h, 48h and 72h after the operation. If the patient is discharged 72h after the patient is discharged, it may not be assessed.
    Simple Mental State Examination (MMSE) Scale score
    The total score of Simple Mental State Examination Scale (MMSE) is 30,the higher the score, the better the cognitive function.
    Hospital Anxiety and Depression (HAD) Scale score
    Hospital Anxiety and Depression Scale (HAD) includes anxiety measure(7questions,0-21pionts) and depression measure(7 questions,0-21pionts),the higher the score, the more severe thesymptoms.

    Full Information

    First Posted
    April 6, 2021
    Last Updated
    April 6, 2021
    Sponsor
    Chinese PLA General Hospital
    Collaborators
    Jiangsu Provincial People's Hospital, Beijing Hospital, The Affiliated Hospital of Qingdao University, Renmin Hospital of Wuhan University, First Affiliated Hospital Xi'an Jiaotong University, First Affiliated Hospital, Sun Yat-Sen University, Shengjing Hospital, Southern Medical University, China
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04837170
    Brief Title
    Safety and Efficacy Evaluation of S (+) - Ketamine in Adults
    Official Title
    Safety and Efficacy Evaluation of S（+）-Ketamine for Postoperative Acute Pain in Adults in Perioperative Settings: A Multicenter, Randomized, Open-label, Active Controlled Pragmatic Clinical Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2021
    Overall Recruitment Status
    Unknown status
    Study Start Date
    May 1, 2021 (Anticipated)
    Primary Completion Date
    June 1, 2022 (Anticipated)
    Study Completion Date
    June 30, 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Chinese PLA General Hospital
    Collaborators
    Jiangsu Provincial People's Hospital, Beijing Hospital, The Affiliated Hospital of Qingdao University, Renmin Hospital of Wuhan University, First Affiliated Hospital Xi'an Jiaotong University, First Affiliated Hospital, Sun Yat-Sen University, Shengjing Hospital, Southern Medical University, China

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    A multicenter, randomized, open-label, active controlled pragmatic clinical trial that evaluates the safety and efficacy of S (+) -ketamine for postoperative acute pain in adults in perioperative settings.
    Detailed Description
    Patients often suffer acute pain after operation ，which may affect the recovery. Opioid such as morphine is the most commonly analgesic drugs, but opioid has many obviously adverse reactions ,for example respiratory depression,circulation inhibition,tolerance, addiction, nausea, vomiting, pruritus, etc. S (+) - ketamine has been described to decrease acute pain and opioid consumption,but it needs to confirm for chinese patients undergoing surgery. Objective:Evaluate the efficacy and safety of S (+) - ketamine on acute perioperative pain for chinese adult patients,and look for the best dosage, mode of administration, timing, and compatibility ,as well explore the effect of S (+) - ketamine on postoperative delirium,anxiety ,depression and cognitive dysfunction.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Postoperative Pain, Adults, Anesthesia
    Keywords
    S-ketamine,Esketamine,S (+) - ketamine, Acute Pain, Depression, Anxiety, Delirium, Hyperalgesia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Model Description
    Experimental group : Control group=2:1
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    12000 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    S (+)-Ketamine group
    Arm Type
    Experimental
    Arm Description
    Drug: Conventional therapy + S (+)-Ketamine In principle, there are no specific restrictions on the dosage, mode of administration, timing, and compatibility of S-ketamine hydrochloride injection,but the recommended dosage is given, which is lower than the dosage specified in the instructions. Recommended use and dosage of S (+)-Ketamine: Bolus intravenous injection before skin incision, the dose is 0.1~0.5 mg/kg; Bolus intravenous injection (dose 0.1~0.5 mg/kg) before skin incision +continuous intravenous infusion (dose of 0.1~0.25 mg/kg/h) during operation; Continuous intravenous infusion after surgery with a dose of 0.02~0.1 mg/kg/h for 24~48 h.
    Arm Title
    Control group
    Arm Type
    Active Comparator
    Arm Description
    Drug: Conventional therapy Receiving conventional therapy without S (+)-Ketamine hydrochloride injection. There is no restrictions in drugs, doses and incompatibility, the researchers can choose appropriate medication regimens based on clinical practice, but other NMDA receptor antagonists are not be allowed to use, such as dextromethorphan and amantadine.
    Intervention Type
    Drug
    Intervention Name(s)
    Conventional therapy + S (+)-Ketamine
    Other Intervention Name(s)
    Conventional therapy + S-ketamine, Conventional therapy + Esketamine
    Intervention Description
    Patients who undergo general anesthesia using S(+)-ketamine hydrochloride for anesthesia induction,maintenance or postoperative analgesia.
    Intervention Type
    Drug
    Intervention Name(s)
    Conventional therapy
    Other Intervention Name(s)
    Routine treatment
    Intervention Description
    Receiving conventional therapy without S (+)-Ketamine hydrochloride injection. There is no restrictions in drugs, doses and incompatibility, the researchers can choose appropriate medication regimens based on clinical practice, but other NMDA receptor antagonists are not be allowed to use, such as dextromethorphan and amantadine.
    Primary Outcome Measure Information:
    Title
    The area under the broken line of NRS score
    Description
    The score of Numerical Rating Scale(NRS) is 0-10, the higher the score, the more severe the pain.
    Time Frame
    Hour 0-48 after surgery
    Title
    Opioid consumption
    Description
    Total opioid consumption(conversion to equivalent morphine)
    Time Frame
    Hour 0-48 after surgery
    Secondary Outcome Measure Information:
    Title
    NRS pain scores
    Description
    The score of Numerical Rating Scale(NRS) is 0-10, the higher the score, the more severe the pain.
    Time Frame
    Hour 0-48 after surgery
    Title
    Time of first rescue analgesia
    Description
    The time from the end of the operation to the first rescue analgesics after the operation. Rescue analgesia refers to the analgesia according to the patient's requirements in addition to routine postoperative analgesia.
    Time Frame
    Hour 0-48 after surgery
    Title
    The incidence of rescue analgesia
    Description
    The incidence of rescue analgesia within 48h after surgery
    Time Frame
    Hour 0-48 after surgery
    Title
    Recovery time
    Description
    The time from the end of the operation to recovery(can be awakened)
    Time Frame
    Day 0
    Title
    The incidence of unexpected intraoperative events
    Description
    Unexpected events during operation include intraoperative cough, laryngeal spasm, body movement, tachycardia,decreased oxygen saturation, respiratory depression, bradycardia, hypertension and hypotension.
    Time Frame
    Intraoperative
    Title
    The Patient Efficacy Questionnaire (IPOQ ) scores
    Description
    Patient Efficacy Questionnaire (IPOQ ) scale include 13 questions , each question's score is 0-10 or 0-100%, it involves postoperative pain, mood and quality of life. The higher the score, the more severe the pain symptoms.
    Time Frame
    Hour 48 after surgery
    Title
    The incidence of adverse events after surgery
    Description
    The incidence of adverse events from the end of the operation to 48h after surgery. Including nausea, vomiting, increased secretions, dizziness, oversedation, infection,anesthetic awareness, nightmares, restlessness, pruritus, disorientation, delirium, respiratory depression, diplopia, diarrhea, intestinal obstruction, urinary retention, gastroesophageal reflux, constipation, chills, hallucinations, etc.
    Time Frame
    Hour 0-48 after surgery
    Title
    Pharmacoeconomic indicators
    Description
    Calculating incremental cost-effectiveness ratio （ICER）based on cost-effectiveness analysis.
    Time Frame
    Hour 48 after surgery
    Title
    Incidence of postoperative delirium
    Description
    The Chinese version of the 3D-CAM scale is used for the diagnosis of delirium, and the assessment will be carried out at 24h, 48h and 72h after the operation. If the patient is discharged 72h after the patient is discharged, it may not be assessed.
    Time Frame
    Hour 0-48 after surgery
    Title
    Simple Mental State Examination (MMSE) Scale score
    Description
    The total score of Simple Mental State Examination Scale (MMSE) is 30,the higher the score, the better the cognitive function.
    Time Frame
    Hour 48 after surgery
    Title
    Hospital Anxiety and Depression (HAD) Scale score
    Description
    Hospital Anxiety and Depression Scale (HAD) includes anxiety measure(7questions,0-21pionts) and depression measure(7 questions,0-21pionts),the higher the score, the more severe thesymptoms.
    Time Frame
    Hour 48 after surgery

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 1. Age ≥18 years old; 2. Scheduled for elective digestive tract surgery, gynecological surgery, urological surgery, thoracic surgery, orthopedic limb surgery, orthopedic spine surgery or body surface surgery (thyroid surgery or breast surgery), head and neck surgery; 3. ASA score Ⅰ～Ⅲ; 4. The informed consent form was signed by the patients. Exclusion Criteria: 1. The expected length of hospital stay of the patient is less than 48h; 2. Patients expected to be admitted to the ICU after surgery; 3. Patients expected to return to the ward with tracheal catheter after surgery; 4. Be allergic to S (+) - ketamine; 5. Patients with severe disorder of consciousness or mental system diseases (schizophrenia, mania, bipolar disorder, psychosis, etc.) or cognitive dysfunction; 6. Patients with a history of severe cardiovascular disease (congestive heart failure, severe angina attack, or unstable angina or myocardial infarction within 6 months); 7. Patients during pregnancy or lactation; 8. Patients with MMSE score <18 points; 9. Patients with any of the following contraindications of S (+) - ketamine: Patients with risk of serious rise of blood pressure or intracranial pressure; Patients with high intraocular pressure (glaucoma) or penetrating ocular trauma; Patients with poorly controlled or untreated hypertension (Resting systolic blood pressure greater than 180 mmHg, or resting diastolic blood pressure greater than 100mmHg); Patients with untreated or undertreated hyperthyroidism.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Weidong Mi, MD
    Phone
    8613381082966
    Email
    wwdd1962@aliyun.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Hong Wang, MD
    Phone
    8613661363231
    Email
    301wh@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Weidong Mi, MD
    Organizational Affiliation
    Chinese PLA General Hospital
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    34916327
    Citation
    Wang H, Duan CY, Huang WQ, Zhao P, Zhou LZ, Liu YH, Liu CM, Chu HC, Wang Q, Diao YG, Hua Z, Meng QT, Li H, Zhang XY, Mi WD, Chen PY. Perioperative intravenous S(+)-ketamine for acute postoperative pain in adults: study protocol for a multicentre, randomised, open-label, positive-controlled, pragmatic clinical trial (SAFE-SK-A trial). BMJ Open. 2021 Dec 16;11(12):e054681. doi: 10.1136/bmjopen-2021-054681.
    Results Reference
    derived

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    Safety and Efficacy Evaluation of S (+) - Ketamine in Adults

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