Erythromycin in Septic Patients: Immunomodulatory Role and Clinical Impact

NCT04665089 | Completed

• 1 other identifier: Rabta
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

In sepsis and septic shock, the host response is characterized by a complex of immune-inflammatory reactions; triggered and activated by microbial components. These reactions are controlled by a balance of pro-inflammatory cytokines and anti-inflammatory cytokines. The imbalance of this immune response is a source of organ dysfunction; major prognostic factor during septic condition. This pretext has created the need for therapies aimed to modulate the overstated of host response. During the past 2 decades, macrolide molecules proved interest to be immunomodulatory agents; due beyond their antibacterial activity. Their regulatory role in the production of cytokines was demonstrated in the management of severe acute community pneumonia. The investigators hypothesize that the adjunction of macrolides to standard therapy in patients with sepsis or septic shock is associated to a favorable immunomodulatory and clinical effects.

Conditions

Sepsis; Septic Shock; Immunoinflammatory Response

Keywords

sepsis; erythromycin; immunity; inflammation; mortality

Outcome Measures

Primary Outcomes (1)

• Change of TNF α / IL-10 ratio

  The pro-inflammatory / anti-inflammatory balance will be estimated by measuring the TNF α / IL-10 ratio at baseline and that at day 6. The difference (Δ) of TNF α / IL-10 ratio between day 0 (or baseline) and day 6 will be calculated in each arm then compared between the 2 arms.

  Change from Baseline TNF α / IL-10 ratio at 6 days

Secondary Outcomes (4)

• mortality

  28 days

• Procalcitonine

  At day 0 and day 6 of inclusion

• vasopressors requirement in mg/H

  during follow-up, an average of 28 days

• vasopressors requirement in days

  during follow-up, an average of 28 days

Study Arms (2)

Erythromycin arm

ACTIVE COMPARATOR

The erythromycin arm (n=55) receives, in addition to the standard antimicrobial therapy, erythromycin 1 g three times per day intravenously: each gram is diluted in 250 ml of 5% glucose serum to be administered over 1 hour for 5 days.

Drug: Erythromycin

Placebo arm

PLACEBO COMPARATOR

The placebo arm (n=55) receives, in addition to the standard antimicrobial therapy, isotonic saline, intravenously, 20 ml diluted in 250 ml of 5% glucose serum to be administered over 1 hour for 5 days.

Drug: Erythromycin

Interventions

Erythromycin DRUG

Before each intervention (either at inclusion: day 0) and after the end of 5 days of erythromycin or placebo (day 6), the following dosages will be performed: * Pro-inflammatory cytokine (TNF alpha) * Anti-inflammatory cytokine (IL-10) * Procalcitonin (PCT) Then, analysis of the variations in the TNF/ IL-10 ratio, the blood count, CRP and PCT parameters (between Day 0 and Day 6)

Also known as: specific dosages

Erythromycin arm; Placebo arm

Eligibility Criteria

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

You may qualify if:

• a patient in whom the diagnosis of sepsis or septic shock is diagnosed (According to the definitions updated by the sepsis 3 consensus in 2016)

You may not qualify if:

• Macrolide use for another indication.
• Known allergy to macrolides.
• A corrected QT prolonged (\> 440 ms for man and 460 ms for woman) or taking drugs with an increased risk of QT prolongation.
• QT prolongation attributed to erythromycin
• Underlying dysimmunity (unbalanced diabetes, autoimmune disease, etc.)
• Pregnant or breastfeeding woman.
• Death or discharge while participating in the protocol (day 0 to day 6)
• Non-compliance with the protocol

Sponsors & Collaborators

• Tunis University: lead

Study Sites (1)

intensive care unit of the University Hospital Center La Rabta

Tunis, 1007, Tunisia

Location

Related Publications (1)

• Trifi A, Tlili B, Kallel Sellami M, Feki M, Mehdi A, Seghir E, Messaoud L, Abdellatif S, Ben Lakhal S. Immunologic effect and clinical impact of erythromycin in septic patients: A randomized clinical trial. J Crit Care. 2024 Jun;81:154533. doi: 10.1016/j.jcrc.2024.154533. Epub 2024 Feb 14.

  PMID: 38359518 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic; Inflammation

Interventions

Erythromycin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: single-blind randomized clinical trial comparing 2 arms: erythromycin versus a placebo

Study Record Dates

• First Submitted: November 20, 2020
• First Posted: December 11, 2020
• Study Start: January 1, 2022
• Primary Completion: January 30, 2023
• Study Completion: April 30, 2023
• Last Updated: May 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)