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

Phase 4

• Conditions: Adults; Anesthesia; Postoperative Pain
• Interventions: Drug: Conventional therapy + S (+)-Ketamine; Drug: Conventional therapy

• Registration Number: NCT04837170
• Lead Sponsor: Chinese PLA General Hospital

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 Timeline

• Status Verified: 2021-04
• Study First Submitted: 2021-04-06
• Study First Submitted QC: 2021-04-06
• Last Update Submitted: 2021-04-06
• Study First Posted: 2021-04-08
• Last Update Posted: 2021-04-08
• Study Start: 2021-05-01
• Primary Completion: 2022-06-01
• Study Completion: 2022-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12000

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:

  10. Patients with risk of serious rise of blood pressure or intracranial pressure;

  11. Patients with high intraocular pressure (glaucoma) or penetrating ocular trauma;

  12. Patients with poorly controlled or untreated hypertension (Resting systolic blood pressure greater than 180 mmHg, or resting diastolic blood pressure greater than 100mmHg);

  13. Patients with untreated or undertreated hyperthyroidism.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
S (+)-Ketamine group	Conventional therapy + S (+)-Ketamine	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.
Control group	Conventional therapy	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Simple Mental State Examination (MMSE) Scale score	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.
NRS pain scores	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	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	Hour 0-48 after surgery	The incidence of rescue analgesia within 48h after surgery
The Patient Efficacy Questionnaire (IPOQ ) scores	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	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.
Recovery time	Day 0	The time from the end of the operation to recovery(can be awakened)
The incidence of unexpected intraoperative events	Intraoperative	Unexpected events during operation include intraoperative cough, laryngeal spasm, body movement, tachycardia,decreased oxygen saturation, respiratory depression, bradycardia, hypertension and hypotension.
Pharmacoeconomic indicators	Hour 48 after surgery	Calculating incremental cost-effectiveness ratio （ICER）based on cost-effectiveness analysis.
Incidence of postoperative delirium	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.
Hospital Anxiety and Depression (HAD) Scale score	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.