Modulation of Microbiota Metabolism in Cardiac Surgery Patients

NCT ID: NCT04921436

Last Updated: 2024-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-03
• Study Completion Date: 2023-07-31

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.

Conditions

Multiple Organ Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

cardiac surgery

Intervention Type: PROCEDURE

prophylactic use of antibiotic-inhibitors

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)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

cardiac surgery

prophylactic use of antibiotic-inhibitors

Intervention Type: PROCEDURE

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federal Research and Clinical Centre of Intensive Care Medicine and Rehabilitology

OTHER

Sponsor Role: collaborator

Petrovsky National Research Centre of Surgery

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MAXIM BABAEV, D.Sc.

Role: PRINCIPAL_INVESTIGATOR

Petrovsky National Research Centre of Surgery

Locations

Petrovsky National Reasearch Centre of Surgery

Moscow, , Russia

Countries

Russia

Other Identifiers

10031967MM

Identifier Type: -

Identifier Source: org_study_id