Modulation of Microbiota Metabolism in Cardiac Surgery Patients (MMMMODCS)

Modulation of Microbiota Metabolism in Cardiac Surgery Patients With at High Risk of Postoperative Multiple Organ Dysfunctions

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.

Study Overview

• Status: Completed
• Conditions: Multiple Organ Dysfunction
• Intervention / Treatment: Procedure: cardiac surgery

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119991
    • Petrovsky National Reasearch Centre of Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cardiac surgery patients with preventive treatment; In addition to standard antibiotic prophylaxis (cefazolin 2 g 60 minutes before skin incision and 2 g 3 times a day after surgery), the following antibiotic regimens will be used perioperatively: Doxycycline (the day before surgery 200 mg and 100 mg on days 1 and 2 after surgery) or Rimfampicin (150 mg 2 times a day before and after surgery) + Gentamicin (240 mg 3 times a day before and 2 days after surgery) or Clarithromycin (500 mg once daily for up to 2 days after surgery). The route of administration (oral / intravenous) will depend on the condition of the patient.	Procedure: cardiac surgery; prophylactic use of antibiotic-inhibitors
No Intervention: cardiac surgery patients without preventive treatment; standard antibiotic prophylaxis (cefazolin 2 g 60 minutes before skin incision and 2 g 3 times a day after surgery)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AMM level	the frequency of detecting patients with an AMM level in the blood serum of no more than 3.5 μmol / l (according to the results of GC-MS analysis)	3 - 6 days after surgery
the duration of stay in the ICU	the frequency of detecting patients	one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	the frequency of detecting patients	6 days after surgery

Collaborators and Investigators

• Sponsor: Petrovsky National Research Centre of Surgery
• Collaborators: Federal Research and Clinical Centre of Intensive Care Medicine and Rehabilitology
• Investigators: Principal Investigator: MAXIM BABAEV, D.Sc., Petrovsky National Research Centre of Surgery

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2021
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: May 24, 2021
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Estimated): November 25, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: cardiac surgery; microbiota;; sepsis;; antibiotics
• Other Study ID Numbers: 10031967MM

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No