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

• ClinicalTrials.gov Identifier: NCT04837170
• Recruitment Status: Not yet recruiting
• First Posted: April 8, 2021
• Last Update Posted: April 8, 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
• Information provided by (Responsible Party): Weidong Mi, Chinese PLA General Hospital

Tracking Information

• First Submitted Date: April 6, 2021
• First Posted Date: April 8, 2021
• Last Update Posted Date: April 8, 2021
• Estimated Study Start Date: May 1, 2021
• Estimated Primary Completion Date: June 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 6, 2021)

• The area under the broken line of NRS score [ Time Frame: Hour 0-48 after surgery ]
  The score of Numerical Rating Scale(NRS) is 0-10, the higher the score, the more severe the pain.
• Opioid consumption [ Time Frame: Hour 0-48 after surgery ]
  Total opioid consumption(conversion to equivalent morphine)

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 6, 2021)

• NRS pain scores [ Time Frame: Hour 0-48 after surgery ]
  The score of Numerical Rating Scale(NRS) is 0-10, the higher the score, the more severe the pain.
• Time of first rescue analgesia [ Time Frame: Hour 0-48 after surgery ]
  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 [ Time Frame: Hour 0-48 after surgery ]
  The incidence of rescue analgesia within 48h after surgery
• Recovery time [ Time Frame: Day 0 ]
  The time from the end of the operation to recovery(can be awakened)
• The incidence of unexpected intraoperative events [ Time Frame: Intraoperative ]
  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 [ Time Frame: Hour 48 after surgery ]
  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 [ Time Frame: Hour 0-48 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 [ Time Frame: Hour 48 after surgery ]
  Calculating incremental cost-effectiveness ratio （ICER）based on cost-effectiveness analysis.
• Incidence of postoperative delirium [ Time Frame: Hour 0-48 after surgery ]
  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 [ Time Frame: Hour 48 after surgery ]
  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 [ Time Frame: Hour 48 after surgery ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Experimental group : Control group=2:1

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Postoperative Pain
• Adults
• Anesthesia

Intervention

• Drug: Conventional therapy + S (+)-Ketamine
  Patients who undergo general anesthesia using S(+)-ketamine hydrochloride for anesthesia induction,maintenance or postoperative analgesia.
  Other Names:

  • Conventional therapy + S-ketamine
  • Conventional therapy + Esketamine
• 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.
  Other Name: Routine treatment

Study Arms

• Experimental: S (+)-Ketamine group

  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:

  1. Bolus intravenous injection before skin incision, the dose is 0.1~0.5 mg/kg;
  2. 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;
  3. Continuous intravenous infusion after surgery with a dose of 0.02~0.1 mg/kg/h for 24~48 h.
  Intervention: Drug: Conventional therapy + S (+)-Ketamine
• Active Comparator: Control group
  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: Drug: Conventional therapy

• Publications *: 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.

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 6, 2021): 12000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2022
• Estimated Primary Completion Date: June 1, 2022 (Final data collection date for primary outcome measure)

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:

  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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Weidong Mi, MD; 8613381082966; wwdd1962@aliyun.com

Contact: Hong Wang, MD; 8613661363231; 301wh@163.com

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04837170
• Other Study ID Numbers: SAFE-SK-A
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Weidong Mi, Chinese PLA General Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Chinese PLA General Hospital
• Original Study Sponsor: Same as current

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

Investigators

• Study Chair: Weidong Mi, MD; Chinese PLA General Hospital

• PRS Account: Chinese PLA General Hospital
• Verification Date: April 2021