Clinical trial NCT04837170: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Postoperative Pain
Adults
Anesthesia
Keywords: S-ketamine,Esketamine,S (+) - ketamine
Acute Pain
Depression, Anxiety
Delirium
Hyperalgesia
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu Provincial People's Hospital
name: Beijing Hospital
name: The Affiliated Hospital of Qingdao University
name: Renmin Hospital of Wuhan University
name: First Affiliated Hospital Xi'an Jiaotong University
name: First Affiliated Hospital, Sun Yat-Sen University
name: Shengjing Hospital
name: Southern Medical University, China
First posted: 2021-04-08
Enrollment: 12000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental group : Control group=2:1
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The area under the broken line of NRS score
timeFrame: Hour 0-48 after surgery
measure: Opioid consumption
timeFrame: Hour 0-48 after surgery
Secondary outcomes:
measure: NRS pain scores
timeFrame: Hour 0-48 after surgery
measure: Time of first rescue analgesia
timeFrame: Hour 0-48 after surgery
measure: The incidence of rescue analgesia
timeFrame: Hour 0-48 after surgery
measure: Recovery time
timeFrame: Day 0
measure: The incidence of unexpected intraoperative events
timeFrame: Intraoperative
measure: The Patient Efficacy Questionnaire (IPOQ ) scores
timeFrame: Hour 48 after surgery
measure: The incidence of adverse events after surgery
timeFrame: Hour 0-48 after surgery
measure: Pharmacoeconomic indicators
timeFrame: Hour 48 after surgery
measure: Incidence of postoperative delirium
timeFrame: Hour 0-48 after surgery
measure: Simple Mental State Examination (MMSE) Scale score
timeFrame: Hour 48 after surgery
measure: Hospital Anxiety and Depression (HAD) Scale score
timeFrame: Hour 48 after surgery
Other outcomes:
Locations:
Study officials:
affiliation: Chinese PLA General Hospital
name: Weidong Mi, MD
role: STUDY_CHAIR
References:
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.