Effect of Intravenous S-ketamine on Opioid Consumption

• ClinicalTrials.gov Identifier: NCT05060068
• Recruitment Status: Recruiting
• First Posted: September 28, 2021
• Last Update Posted: July 20, 2022
• Sponsor: The Second Hospital of Anhui Medical University
• Information provided by (Responsible Party): Yun Wu, The Second Hospital of Anhui Medical University

Study Description

Brief Summary:

Female patients with an American Society of Anesthesia (ASA) physical status I-II, scheduled for elective breast cancer surgery will be included in the study. Subjects will be randomly assigned to one of three groups: the placebo group, the low-dose S-ketamine group, and the high-dose S-ketamine group. The primary outcome is the consumption of sufentanil during the surgery.

Condition or disease	Intervention/treatment	Phase
Breast Cancer Surgery	Drug: S-ketamine (low dose); Drug: Placebo; Drug: S-ketamine (high dose)	Not Applicable

Detailed Description:

All patients will be scheduled to a propofol-remifentanil general anesthesia and receive non-steroid anti-inflammatory drug before incision. Bolus sufentanil will be administered according to the blood pressure, heart rate and bispectral index perioperatively. Patients unable to understand the study procedure or unable to give informed consent, with concurrent analgesic or sedative medication, with history of chronic pain, psychiatric disorders, or alcohol or drug abuse, with an allergy to the study medication, who are pregnant or breast feeding, with a BMI >30 and <18 kg/m2, with severe cardiac, pulmonary, hepatic or renal dysfunction, with intracranial hypertension will be excluded.

Subjects will be randomly assigned to one of three groups: the placebo group, the low-dose S-ketamine group, and the high-dose S-ketamine group. The study medication will be administered in a bolus injected over 30 s after induction, followed by continuous infusion, which started after the initial bolus. The placebo group will receive a bolus of 0.9% saline, followed by continuous infusion of 0.9% saline. The low-dose ketamine group will be administered a bolus of 0.5 mg/kg S-ketamine in saline, followed by 2μg/kg/min S-ketamine in saline, whereas the high-dose ketamine group will be administered a bolus of 0.5 mg/kg S-ketamine in saline, followed by continuous infusion of 4μg/kg/min S-ketamine in saline. The syringes and infusions will be identical for all of the groups and will run at the same rate in all subjects to enable blinding of the investigators. Study medication will be terminated 30 min prior to the end of the surgery. After surgery and in the postanesthesia care unit, patients will be asked about their pain level on a numeric rating scale (NRS), and about the presence of intraoperative awareness, nausea, vomiting, and hallucinations. Rescue analgesia of sufentanil will be provided when NRS ≥ 4 or patients require. Pain level will also be assessed at 0.5, 2, 4, 6, 12 and 24 hour postoperatively as well as 3 and 6 month after the surgery. Depression scale will be evaluated before the surgery and in the 7th postoperative day.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 825 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The syringes and infusions will be identical for all of the groups and will run at the same rate in all subjects to enable blinding of the investigators. Outcomes will be evaluated by anesthesiologists who are blinded to the treatment allocation. Patients, nurses, observers, and the statistician will be blinded to patient allocation throughout the study period.
• Primary Purpose: Treatment
• Official Title: Effect of Intravenous S-ketamine on Opioid Consumption and Postoperative Pain in Patients Undergoing Breast Cancer Surgery：a Multicenter, Randomised, Control Trial
• Actual Study Start Date: October 7, 2021
• Estimated Primary Completion Date: July 7, 2023
• Estimated Study Completion Date: July 7, 2023

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo group; Patients in the placebo group will receive a bolus of 0.9% saline, followed by continuous infusion of 0.9% saline until 30 min prior to the end of the surgery.	Drug: Placebo; Patients in the placebo group will receive a bolus of 0.9% saline, followed by continuous infusion of 0.9% saline until 30 min prior to the end of the surgery.; Other Name: CON
Experimental: Low-dose ketamine group; Patients in the low-dose ketamine group will receive a bolus of 0.5 mg/kg S-ketamine in saline, followed by continuous infusion of 2 μg/kg/min S-ketamine in saline until 30 min prior to the end of the surgery.	Drug: S-ketamine (low dose); Patients in the low-dose ketamine group will receive a bolus of 0.5 mg/kg S-ketamine in saline, followed by continuous infusion of 2 μg/kg/min S-ketamine in saline until 30 min prior to the end of the surgery.; Other Name: LKET
Experimental: High-dose ketamine group; Patients in the low-dose ketamine group will receive a bolus of 0.5 mg/kg S-ketamine in saline, followed by continuous infusion of 4 μg/kg/min S-ketamine in saline until 30 min prior to the end of the surgery.	Drug: S-ketamine (high dose); Patients in the high-dose ketamine group will receive a bolus of 0.5 mg/kg S-ketamine in saline, followed by continuous infusion of 4 μg/kg/min S-ketamine in saline until 30 min prior to the end of the surgery.; Other Name: HKET

Outcome Measures

Primary Outcome Measures :

1. consumption of sufentanil [ Time Frame: during the surgery ]
   the consumption of sufentanil during the surgery.

Secondary Outcome Measures :

1. postoperative pain assessment [ Time Frame: at 0.5, 2, 4, 6, 12 and 24 hours respectively after surgery; Month 3 and Month 6 after surgery ]
   Patients will be asked about their pain level at rest and moving on a numeric rating scale evaluated on a 11-point (0 = no pain, 10 = worst pain imaginable).
2. consumption of analgesics [ Time Frame: in the first 24 hour after surgery ]
   cumulative analgesic consumption after surgery
3. Richmond Agitation-Sedation Scale (RASS) [ Time Frame: 30 minutes after surgery ]
   Richmond Agitation-Sedation Scale is a 10-point scale. The values and definitions for each level of agitation and sedation are displayed as follows: +4, Combative, overtly combative or violent; immediate danger to staff; +3, Very agitation, pulls on or removes tube(s) or catheter(s) or has aggressive behavior toward staff; +2, Agitated, frequent nonpurposeful movement or patient-ventilator dyssynchrony; +1, Restless, anxious or apprehensive but movements not aggressive or vigorous; 0, Alert and calm; -1, Drowsy, not fully alert, but has sustained (more than 10 seconds) awakening, with eye contact, to voice; -2, Light sedation, briefly (less than 10 seconds) awakens with eye contact to voice; -3, Moderate sedation, any movement (but no eye contact) to voice; -4, Deep sedation, no response to voice, but any movement to physical stimulation; -5, Unarousable, no response to voice or physical stimulation
4. sleep quality scale [ Time Frame: sleep quality scale will be assessed in the morning (8:00 am）of first postoperative day ]
   Quality of sleep in the night of surgery day using a 4-point scale (1 = "slept well," 2 = "disturbed sleep," 3 = "nightmares," and 4 = "sleepless") will be recorded.
5. consumption of propofol [ Time Frame: during the surgery ]
   the consumption of propofol during the surgery.
6. consumption of remifentanil [ Time Frame: during the surgery ]
   the consumption of remifentanil during the surgery.
7. length of anesthesia [ Time Frame: at the end of anesthesia ]
   from beginning to the end of anesthesia
8. length of surgery [ Time Frame: at the end of surgery ]
   from beginning to the end of surgery
9. recovery time [ Time Frame: at the time when patients waking up ]
   awakening time from surgery
10. consumption of vasoactive agents [ Time Frame: during the surgery ]
    the consumption of any vasoactive agent (such as phenylephrine, urapidil, ephedrine)
11. blood pressure [ Time Frame: before anesthesia, prior to incision, 5, 10, 30, 60 and 120 minutes after incision, at the end of surgery and 30 minutes after surgery ]
    noninvasive blood pressure
12. heart rate [ Time Frame: before anesthesia, prior to incision, 5, 10, 30, 60 and 120 minutes after incision, at the end of surgery and 30 minutes after surgery ]
    Heart rate of the patients
13. bispectral index [ Time Frame: before anesthesia, prior to incision, 5, 10, 30, 60 and 120 minutes after incision, at the end of surgery and 30 minutes after surgery ]
    Bispectral index during the surgery
14. adverse effects [ Time Frame: through 24 hours after the surgery ]
    The presence of intraoperative awareness, nausea, vomiting, and hallucinations after surgery
15. Edinburgh postnatal depression scale [ Time Frame: before surgery and at the 7th day after surgery ]
    Depression scale generated from Edinburgh postnatal depression scale will be assessed. The minimum value is 0, and the maximum value is 30. The higher score means the higher possibility of depression.
16. ambulation time [ Time Frame: 7 days after surgery ]
    interval time of patients' transit from bed rest to ambulation after surgery
17. hospitalization postoperatively [ Time Frame: two weeks after surgery ]
    days of hospital staying after surgery

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Female patients with an American Society of Anesthesia (ASA) physical status I-II
2. Scheduled for elective breast cancer surgery

Exclusion Criteria:

1. Patients unable to understand the study procedure or unable to give informed consent
2. with concurrent analgesic or sedative medication,
3. with history of chronic pain
4. with history of psychiatric disorders
5. with history of alcohol or drug abuse
6. with an allergy to the study medication
7. who are pregnant or breast feeding
8. with a BMI >30 and <18 kg/m^2
9. with severe cardiac, pulmonary, hepatic or renal dysfunction
10. with intracranial hypertension

Contacts and Locations

Contacts

Contact: Yun Wu, M.D., Ph. D.; +8613865958254; wuyunanyi@163.com

Locations

China

Second Affiliated Hospital of Anhui Medical University; Recruiting

Hefei, China, 230601

Contact: Yun Wu, MD +8613865958254 wuyunanyi@163.com

Sponsors and Collaborators

The Second Hospital of Anhui Medical University

Investigators

• Study Chair: Ye Zhang, M.D., Ph. D.; The Second Hospital of Anhui Medical University

More Information

Publications:

Brinck ECV, Maisniemi K, Kankare J, Tielinen L, Tarkkila P, Kontinen VK. Analgesic Effect of Intraoperative Intravenous S-Ketamine in Opioid-Naive Patients After Major Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Anesth Analg. 2021 Jan;132(1):69-79. doi: 10.1213/ANE.0000000000004729.

Hamp T, Baron-Stefaniak J, Krammel M, Reiter B, Langauer A, Stimpfl T, Plochl W. Effect of intravenous S-ketamine on the MAC of sevoflurane: a randomised, placebo-controlled, double-blinded clinical trial. Br J Anaesth. 2018 Dec;121(6):1242-1248. doi: 10.1016/j.bja.2018.08.023. Epub 2018 Oct 15.

• Responsible Party: Yun Wu, Principal Investigator, The Second Hospital of Anhui Medical University
• ClinicalTrials.gov Identifier: NCT05060068
• Other Study ID Numbers: YX2021-070(F1)
• First Posted: September 28, 2021
• Last Update Posted: July 20, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All IPD that underlie results in a publication are to be shared with other researchers.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: The IPD will become available when summary data are published.
• Access Criteria: Yun Wu and Ye Zhang will review requests and criteria to share IPD. Requests are to be sent by email to wuyunanyi@163.com or zhangye_hassan@sina.com.

• 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

Keywords provided by Yun Wu, The Second Hospital of Anhui Medical University:

breast cancer surgery; S-ketamine; opioid consumption

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Ketamine; Esketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antidepressive Agents; Psychotropic Drugs