Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT05180318 |
| Other study ID # |
WJ-2020-01 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2024 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
April 2024 |
| Source |
Wuhan Union Hospital, China |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
Esketamine is a new antidepressant approved by the US Food and Drug Administration (FDA) in
2019. It has rapid action and accurate treatment effect for refractory severe depression.
Studies have shown that esketamine also has significant anti-inflammatory effects. The
investigators' previous study found that esketamine has a good preventive effect on
inflammatory response, but the effect of preoperative preadministration of esketamine on
postoperative systemic immune function and systemic inflammatory response is not clear.
Clinical studies have shown that esketamine (0.25 mg/kg, 40 min infusion time) can rapidly
improve the depressive symptoms of patients with treatment-resistant depression. Esketamine
is shown to be able to play a neuroprotective role by reducing glial cell activation and the
production of inflammatory cytokines such as tumor necrosis factor (TNF-α) and interleukin-6
(IL-6). Esketamine at a dose of 0.2 mg/kg or 0.4 mg/kg has significant antidepressant effects
in the treatment of resistant depression. The antidepressant effects of esketamine may be
closely related to its anti-inflammatory effect. During cardiopulmonary bypass surgery,
anesthesia induction was supplemented with 1-3 mg/kg esketamine, anesthesia maintenance was
supplemented with 2-3 mg/kg/h esketamine, anesthesia maintenance time was 283 minutes, the
total amount of esketamine was 1580mg on average. Esketamine decreased plasma levels of IL-6
(6 h after opening the aorta) and IL-8 (1 and 6 h after opening the aorta) and increased
plasma levels of IL-10 (1 h after opening the aorta). In the investigators' preliminary study
on the role of esketamine in systemic inflammation induced by lipopolysaccharide (LPS), the
investigators found that in systemic LPS (5 mg/kg)-induced systemic inflammation model,
esketamine (10 mg/kg, IP) was administrated twice 24 hours before LPS administration and 10
minutes after LPS administration. The plasma levels of IL-6, IL-17A and interferon γ (IFN-γ)
were significantly decreased 24 h after LPS administration in mice. Single administration of
esketamine 10 min after LPS administration did not significantly reduce the plasma levels of
IL-6 and IL-17A at 24 h. The investigators further found that in mice with LPS (8
mg/kg)-induced systemic inflammation, twice intraperitoneal administration of esketamine (10
mg/kg, IP) 24 hours before LPS administration and 10 minutes after LPS administration also
significantly reduced the plasma levels of IL-17A 24 hours after LPS administration.
Surgery-induced trauma could cause significant inflammatory responses, manifested by
increased expression of pro-inflammatory cytokines. Studies have found that ketamine at a
dose of 0.5 mg/kg administrated immediately before chest surgery could reduce the plasma
levels of IL-6 and C-reactive protein 24 hours after surgery. However, it remains unclear
whether preoperative and immediate postoperative administration of esketamine could improve
postoperative immune function and alleviate systemic inflammatory response.
The investigators will include patients subjected to elective surgery strictly according to
the inclusion and exclusion criteria to investigate whether preoperative and immediate
postoperative administration of esketamine has postoperative anti-inflammatory effects on
postoperative delirium, postoperative pain, and postoperative sleep, as well as on total
length of hospital stay, in-hospital infection complications, in-hospital mortality, and
90-day readmission rates. Prophylactic administration of esketamine before surgery is
expected to provide a new therapeutic strategy for alleviating postoperative systemic
inflammation and improving postoperative immune suppression.
Enrolled patients were randomly assigned to two groups: the esketamine preadministration
group and the placebo control group. Esketamine at a dose of 0.25 mg/kg (40 min infusion
time) or normal saline was given intravenously 24-36 hours before surgery, and esketamine at
a dose of 0.25 mg/kg (40 min infusion time) or normal saline was given intravenously
immediately after surgery.
Seven tubes of venous blood were collected and sent to the laboratory and immunology
department of Union Hospital affiliated to Tongji Medical College, Huazhong University of
Science and Technology, 24 hours before and after the first administration of esketamine, and
seven tests including blood routine, coagulation, liver function, kidney function,
electrolytes, C-reactive protein, myocardial enzyme, BNP, lymphocyte subsets and cytokines
were performed. A tube of venous blood was taken at each of the two time points in the study
and centrifuged to obtain plasma, which was frozen and stored at -80℃ for ELISA detection of
ANP.
If the adverse events of esketamine appear during the study, patients or authorized client
withdraw from the study actively, or drugs that seriously affect systemic inflammation and
immune function (such as non-steroidal anti-inflammatory drugs, immunosuppressants,
immunoenhancers, high doses of hormones (more than 10mg prednisolone per day or equivalent
dose of other hormones, etc.) were used in clinical treatment, the study will be terminated.
In this study, adverse reactions were evaluated daily and closely monitored within 7 days
after inclusion.
