The Effects of Gut Micribiota Disruption on the Immune Response After Open Heart Surgery

NCT03939273 | Unknown DMC

• 2 other identifiers: The REMEDI trial2019-000964-54
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

In this randomized, double-blind, placebo-controlled study, the investigators will assess whether preoperative disruption of the gut microbiota by a course of broad spectrum antibiotics will attenuate the postoperative systemic inflammatory response after on-pump cardiac surgery

Conditions

Systemic Inflammatory Response Syndrome; Postoperative Shock; Coronary Artery Disease; Extracorporeal Circulation; Complications

Keywords

Systemic Inflammation; Microbiome; CABG; Coronary Artery Bypass Graft; Innate Immunity; Gut microbiota

Outcome Measures

Primary Outcomes (1)

• Between group differences in Area Under the Curve (AUC) of the time-concentration curve of interleukin (IL)-6 plasma concentrations.

  Blood samples will be obtained at predefined time points during and after surgery to assess plasma levels (in pg/mL) of circulating inflammatory mediators. To assess between group differences, the AUC of the time-concentration curve (expressed in arbitrary units) of each inflammatory mediator will be calculated.

  During surgery and up to 24 hours after surgery

Secondary Outcomes (1)

• Between group differences in AUC of the time-concentration curve of other inflammatory mediators.

  During surgery and up to 24 hours after surgery

Study Arms (2)

Active group

ACTIVE COMPARATOR

A preoperative seven day course of oral ciprofloxacin 500 mg twice a day, oral vancomycin 500 mg thrice per day, oral metronidazole 500 mg thrice per day and a six day course of oral fluconazole 200 mg once per day.

Drug: Vancomycin Oral; Drug: Metronidazole Oral; Drug: Ciprofloxacin Pill; Drug: Fluconazole Oral Product

Control group

PLACEBO COMPARATOR

A preoperative seven day course of placebo, consisting of pills and capsules identical in appearance and number to the active group

Drug: Placebos

Interventions

Vancomycin Oral DRUG

500 mg thrice per day for seven days

Active group

Metronidazole Oral DRUG

500 mg thrice per day for seven days

Active group

Ciprofloxacin Pill DRUG

500 mg twice per day for seven days

Active group

Fluconazole Oral Product DRUG

200 mg once per day for six days

Active group

Placebos DRUG

seven day course of placebo tablets and capsules identical in appearance and number to active treatment

Control group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Scheduled for elective on-pump cardiac surgery.
• Written informed consent to participate in this trial prior to any study-mandated procedure

You may not qualify if:

• Use of any antibiotic or antifungal therapies within 30 days prior to surgery
• History of inflammatory bowel disease
• History of bowel resection and / or short bowel syndrome
• Pre-operative creatinine clearance \< 50 ml/min
• Severe hepatic impairment
• Immune compromised
• Solid organ transplantation
• Known HIV
• Pregnancy
• Use of immunosuppressive drugs
• Emergency surgery
• Haematological disorders
• Disorders from myeloid and / or lymphoid origin
• Leucopenia
• Known hypersensitivity to any of the investigational and/or non-investigational products or their excipients.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Medical Centre

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

MeSH Terms

Conditions

Systemic Inflammatory Response Syndrome; Coronary Artery Disease

Interventions

Vancomycin; Metronidazole; Ciprofloxacin

Condition Hierarchy (Ancestors)

Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Peter Pickkers, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aron Jansen, MD

CONTACT

+31 24 36 55618; aron.jansen@radboudumc.nl

Quirine Habes, MD

CONTACT

quirine.habes@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized double-blind placebo-controlled trial

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: May 6, 2019
• Study Start: March 1, 2022
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: March 12, 2021

Record last verified: 2021-03

Locations

NL (1)