Prophylactic Effects of Esketamine in Surgical Patients

NCT05180318 | Withdrawn Phase 4

• 1 other identifier: WJ-2020-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Evidences have showing that esketamine has anti-inflammatory and therapeutic effects on depression and cardiac surgery. The investigators' preliminary results suggest that combined prophylactic and therapeutic use of esketamine could decrease the plasma levels of pro-inflammatory cytokines after LPS-induced endotoxemia. The investigators also found that combined prophylactic and therapeutic use of esketamine could attenuate systemic inflammation and inflammatory multi-organ injury in mice after CLP-induced lethal sepsis. Surgical trauma could elicit a marked inflammatory response with increased expression of pro-inflammatory cytokines, as well as postoperative immunosuppression. However, it remains unclear whether combined prophylactic and therapeutic use of esketamine could improve postoperative immunosuppression and alleviates systemic inflammatory response. This project aims to study whether combined prophylactic and therapeutic use of esketamine could improve the decreased number of lymphocyte subsets and increased plasma pro-inflammatory cytokines.

Conditions

Surgical Injury

Keywords

Esketamine; Inflammatory cytokines; Lymphocyte subsets

Outcome Measures

Primary Outcomes (2)

• Recovery percentage of peripheral blood lymphocyte subsets

  CD3+、CD3+CD4+、CD3+CD8+、CD3-CD16+CD56+ NK cells、CD19+ B cells

  24 hours after surgery

• Deterioration percentage of peripheral blood pro-inflammatory cytokines

  IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ、TNF-α

  24 hours after surgery

Secondary Outcomes (6)

• Plasma levels of atrial natriuretic peptide (ANP)

  At 24 hours after surgery

• Recovery percentage of peripheral blood neutrophil to lymphocyte ratio (NLR)

  At 24 hours after surgery

• Total length of hospital stay

  Up to 24 weeks

• Infectious complications after inclusion during hospitalization

  Up to 24 weeks

• 28-day mortality rate

  Up to 28 days after inclusion

Study Arms (2)

0.9% saline preadministration group

PLACEBO COMPARATOR

0.9% saline will be given intravenously 24-36 hours before operation and immediately after operation

Drug: 0.9% saline

Esketamine preadministration group

EXPERIMENTAL

Esketamine (0.25 mg/kg) will be given intravenously 24-36 hours before surgery (infusion time: 40 min) and immediately after surgery (infusion time: 40 min).

Drug: Esketamine Hydrochloride 28 Mg in 0.2 mL NASAL SOLUTION [Spravato]

Interventions

Esketamine Hydrochloride 28 Mg in 0.2 mL NASAL SOLUTION [Spravato] DRUG

Esketamine (0.25 mg/kg) will be given intravenously 24-36 hours before surgery (infusion time: 40 min) and immediately after surgery (infusion time: 40 min).

Also known as: (S)-ketamine

Esketamine preadministration group

0.9% saline DRUG

0.9% saline

0.9% saline preadministration group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-80 years old without restriction of gender, race, religion, creed or nationality;
• Surgery with general anesthesia operation with estimated operation time of at least 2 hours;
• Patients and/or their family members know and agree to participate in the trial.

You may not qualify if:

• Local anesthesia surgery;
• Being admitted to ICU immediately after surgery;
• Pregnant or breastfeeding;
• History of solid organ or bone marrow transplantation;
• Diseases that may affect immune-related indicators, including autoimmune diseases (rheumatoid arthritis and systemic lupus erythematosus, etc.), and malignant hematological tumours (leukaemia and lymphoma, etc.);
• Acute brain injury, including traumatic brain injury, subarachnoid hemorrhage, acute ischemic stroke, acute intracranial hemorrhage and acute intracranial infection;
• Chronic nephrosis;
• Acute myocardial infarction or severe heart failure (NYHA: Grade 4);
• Severe chronic liver disease (child-Pugh: Grade C);
• Deafness, aphasia, mental illness or severe cognitive impairment;
• Endotracheal intubation could not be removed within 24 hours after surgery
• Patients and/or their family members refuse to participate in the trial.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

MeSH Terms

Conditions

Intraoperative Complications

Interventions

Esketamine; Ketamine; Saline Solution

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Jiancheng Zhang, MD, PhD

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: December 1, 2021
• First Posted: January 6, 2022
• Study Start: October 1, 2024
• Primary Completion: November 30, 2024
• Study Completion: December 31, 2024
• Last Updated: April 29, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Six months after publication.
• Access Criteria: Upon reasonable request.

Locations

CN (1)