Clinical trial NCT04921436: Modulation of Microbiota Metabolism in Cardiac Surgery Patients
Official title: Modulation of Microbiota Metabolism in Cardiac Surgery Patients With at High Risk of Postoperative Multiple Organ Dysfunctions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Organ Dysfunction
Keywords: microbiota;
sepsis;
antibiotics;
cardiac surgery
Lead sponsor: Petrovsky National Research Centre of Surgery
Sponsor class: OTHER
Collaborators: name: Federal Research and Clinical Centre of Intensive Care Medicine and Rehabilitology
First posted: 2021-06-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In group I, antibiotics-inhibitors of microbial metabolism are used in the perioperative period and the next 2 postoperative days The second group uses standard antibiotic prophylaxis
Primary purpose: PREVENTION

Brief summary: An imbalance in the microbiota (most often intestinal) largely determines the onset of a disease state, and often a critical state. Cardiac surgery accompanied by heart failure and hypoperfusion is a proven risk factor for the development of metabolic disorders of the intestinal flora and bacterial translocation. Previously, it was shown that the change in serum concentrations of phenolic metabolites of the intestinal microbiota reflects the dynamics of the severity of the patient's condition and can be used for objective monitoring of treatment. Preoperative analysis of microbial metabolites makes it possible to reliably identify the group of patients with the highest risk of developing postoperative organ dysfunctions. In patients with a baseline level of the sum of phenolic acid concentrations over 3.5 mmol / L, the likelihood of postoperative complications is 10 times higher (OR - 10.5; 95% CI 1.35-81.7, p = 0.026). Reducing the metabolic activity of opportunistic bacteria and the level of aromatic microbial metabolites associated with sepsis through the prophylactic use of antibiotics belonging to the group of protein synthesis inhibitors at the level of bacterial cell ribosomes is of great interest.

Detailed description: MMMMODCS (Modulation of Microbiota Metabolism Multiple Organ Dysfunctions in Cardiac Surgery) is a single-center clinical study, during which it is planned to study the safety and efficacy of the perioperative use of antibiotic inhibitors of protein synthesis at the ribosome level of bacterial cells (hereinafter: antibiotic inhibitors) in patients with the high risk of developing multiple organ dysfunction (MOD) of infectious genesis. The high-risk group is represented by patients who are planned to have surgery on the thoracoabdominal aorta; combined operations on coronary vessels and heart valves; patients with initially low heart ejection fraction (less than 45%). The study was designed to find out if the prophylactic use of a combination of antibiotic inhibitors prevents an increase in concentration (or contributes to a decrease with an initial increase) of aromatic microbial metabolites (AMM) above 3.5 mmol / L and the development of MOD, requiring a long stay in the intensive care unit more than 6 days). After signing an informed consent prior to surgery, patients will be randomized into one of two cohorts: with or without a combination of antibiotic inhibitors.

In a cohort with prophylactic treatment, in addition to standard antibiotic prophylaxis (I, II generation cephalosporins), combinations of the following antibiotic inhibitors (Doxycycline or Rimfampicin + Gentamicin or Clarithromycin) will be used orally or intravenously, depending on the patient's condition.

The AMM level will be measured in blood serum samples on a gas chromatography-mass spectrometer before the operation, on the 3rd and 6th days after the operation. The rest of the indicators will be discussed at the same points.

Eligibility criteria: Inclusion criteria:

* patients with aneurysmal aortic disease / aortic rupture;
* patients with ischemic heart disease and dysfunction of the valves;
* patients with initially low heart ejection fraction (less than 45%).

Exclusion criterion:

* tolerance to antibacterial drugs;
* taking oncological chemotherapy drugs;
* taking probiotics and nutritional supplements within the last month;
* intraoperative complications (shock of any etiology, allergic reactions).

Primary outcomes:
measure: AMM level
timeFrame: 3 - 6 days after surgery
measure: the duration of stay in the ICU
timeFrame: one week
Secondary outcomes:
measure: adverse events associated with taking antibiotics (allergic / anaphylactic reactions); cases of sepsis (according to the criteria of Sepsis-3) / septic shock; patients with SOFA more than 7 points more
timeFrame: 6 days after surgery
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Petrovsky National Reasearch Centre of Surgery
Study officials:
affiliation: Petrovsky National Research Centre of Surgery
name: MAXIM BABAEV, D.Sc.
role: PRINCIPAL_INVESTIGATOR
References: