Clinical trial NCT04800393: The Impact of Inhalation vs Total Intravenous Anesthesia on the Immune Status and Mortality in Patients Undergoing Breast Cancer Surgery: a Prospective Double-Blind Randomized Clinical Trial.
Official title: The Impact of Inhalation vs Total Intravenous Anesthesia on the Immune Status and Mortality in Patients Undergoing Breast Cancer Surgery: a Prospective Double-Blind Randomized Clinical Trial (TeMP - Trial).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anesthesia
Breast Cancer
Keywords: Anesthesia
Breast Cancer
Phagocyte Cell Dysfunction
Immune Suppression
Inhalation anesthesia
volatile anesthesia
total intravenous anesthesia
interleukins
phagocytosis
neutrophil-lymphocyte ratio
natural killers
oncology
Lead sponsor: Moscow Clinical Scientific Center
Sponsor class: OTHER
Collaborators: name: Negovsky Reanimatology Research Institute
First posted: 2021-03-16
Enrollment: 130
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Even decade ago it was believed that the choice method of anesthesia did not affect the course of the oncological process, but recent evidence has begun to emerge that inhalation anesthesia vs TIVA is associated with a higher number of adverse outcomes. Apparently, it makes sense to conduct mRCT in order to assess the effect of IA on immune system in patients operated on for breast cancer comprehensively. The results of that kind of RCT may finally give us an answer whether the choice of anesthesia affects the immune status of patients undergoing surgery for breast cancer. The evaluation of complications and long-term survival will allow to recommend to use or not to use IA for this type of surgery.

Objective: The Impact of Inhalation vs Total Intravenous Anesthesia on the Immune Status and Mortality in Patients Undergoing Breast Cancer Surgery

Detailed description: The power calculation for this study was based on an assessment of Neutrophil-lymphocyte ratio (NLR) in patients undergoing breast cancer resection with total intravenous and inhalation anesthesia in two studies:

1. Cho J.S. et al., 2017 - 48 patients (PMID: 28924368, TIVA group: NLR = 3.37 ± 1.27; inhalation group: NLR = 3.85 ± 1.46)
2. Ní Eochagáin A. et al., 2018 - 116 patients (PMID: 29457215, TIVA group: NLR = 3.20 ± 1.37; inhalation group: NLR = 4.10 ± 1.90).

The pooled mean NLR in the TIVA group is 3.25±1.34, in the inhalation anesthesia group: 4.03±1.78.

Difference in means (effect size): 0.78, for level α=0.05, power 1-β=80% and expected standard deviation of 1.5, 65 patients in each group should be recruited, taking into account a 10% margin (total number of patients: 130).

Eligibility criteria: Inclusion Criteria:

* The age of the patients is from 45 to 74 years;
* Primary operable breast cancer (BC) without prior chemotherapy;
* Cytologically confirmed breast malignant tumor of IA-IIA stages (T1-2, N0, M0);
* Signed informed consent.

Exclusion Criteria:

* Acute cerebrovascular accident (CVA) occurred in the previous 6 months;
* Myocardial infarction (MI) occurred in the previous 6 months;
* Acute arterial thrombosis occurred in the previous 6 months;
* Acute venous thromboembolism occurred in the previous 6 months;
* Subarachnoid hemorrhage occurred during the previous 3 months;
* Chronic kidney disease (CKD) stage 3B-5;
* Сhronic heart failure (NYHA) class 3-4;
* Pregnancy;
* History of another location cancer;
* History of drug addiction;
* Autoimmune diseases in history;
* Post-randomization: withdrawal of informed consent (refusal to continue participating in the study);
* Post-randomization: surgical intervention, performed not in full (verified non-resected lesions in the early p/o period, 2 weeks p/o).

Primary outcomes:
measure: Neutrophil-lymphocyte ratio
timeFrame: 1 hour after surgery
measure: Neutrophil-lymphocyte ratio
timeFrame: 24 hours after surgery
Secondary outcomes:
measure: Matrix metallopeptidase 9
timeFrame: 1 hour after surgery
measure: Matrix metallopeptidase 9
timeFrame: 24 hour after surgery
measure: C-reactive protein
timeFrame: 1 hour after surgery
measure: C-reactive protein
timeFrame: 24 hour after surgery
measure: Natural killer cells of blood (CD3-CD16 +)
timeFrame: 1 hour after surgery
measure: Natural killer cells of blood (CD3-CD16 +)
timeFrame: 24 hour after surgery
measure: Immunoregulatory index of T helpers (CD3 + CD4 +) / cytotoxic T cells (CD3 + CD8 +)
timeFrame: 1 hour after surgery
measure: Immunoregulatory index of T helpers (CD3 + CD4 +) / cytotoxic T cells (CD3 + CD8 +)
timeFrame: 24 hour after surgery
measure: IL-6
timeFrame: 1 hour after surgery
measure: IL-6
timeFrame: 24 hour after surgery
Other outcomes:
measure: T cells of blood (CD3 +)
timeFrame: 1 hour after surgery
measure: T cells of blood (CD3 +)
timeFrame: 24 hours after surgery
measure: T helpers of blood (CD3 + CD4 +)
timeFrame: 1 hour after surgery
measure: T helpers of blood (CD3 + CD4 +)
timeFrame: 24 hours after surgery
measure: Cytotoxic T cells of blood (CD3 + CD8 +)
timeFrame: 1 hour after surgery
measure: Cytotoxic T cells of blood (CD3 + CD8 +)
timeFrame: 24 hours after surgery
measure: B cells of blood (CD19 + CD3-)
timeFrame: 1 hour after surgery
measure: B cells of blood (CD19 + CD3-)
timeFrame: 24 hour after surgery
measure: T cells (CD3 +) + B cells (CD19 + CD3 -) + Natural killer cells (CD3-CD16 +) of blood
timeFrame: 1 hour after surgery
measure: T cells (CD3 +) + B cells (CD19 + CD3 -) + Natural killer cells (CD3-CD16 +) of blood
timeFrame: 24 hours after surgery
measure: Phagocytosis
timeFrame: 1 hour after surgery
measure: Phagocytosis
timeFrame: 24 hours after surgery
measure: IgA
timeFrame: 1 hour after surgery
measure: IgA
timeFrame: 24 hours after surgery
measure: IgM
timeFrame: 1 hour after surgery
measure: IgM
timeFrame: 24 hours after surgery
measure: IgG
timeFrame: 1 hour after surgery
measure: IgG
timeFrame: 24 hours after surgery
measure: Complement component C3
timeFrame: 1 hour after surgery
measure: Complement component C3
timeFrame: 24 hours after surgery
measure: Complement component C4
timeFrame: 1 hour after surgery
measure: Complement component C4
timeFrame: 24 hours after surgery
measure: Overall survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 3 year
measure: Overall survival
timeFrame: 5 year
measure: Disease-free survival
timeFrame: 1 year
measure: Disease-free survival
timeFrame: 3 year
measure: Disease-free survival
timeFrame: 5 year
Locations:
city: Moscow
country: Russian Federation
facility: Moscow Scientific Clinical Center
Study officials:
affiliation: Moscow Scientific Clinical Center
name: Valerii Subbotin, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Negovsky Reanimatology Research Institute
name: Valery Likhvantsev, PhD
role: STUDY_DIRECTOR
References: