Benefit of Clarithromycin in Patients With Severe Infections Through Modulation of the Immune System

• Status: Completed
• Trial end date: 2020-12-19
• Target enrollment: 0
• Participant gender: All

Summary

High mortality associated with sepsis and Multiple Organ Dysfunction Syndrome (MODS) calls for alternative, individualized therapies in selected patients that might benefit form specific interventions. Role of macrolides as potential immunomodulatory treatment in sepsis is promising, but unclear. Subgroup analysis of previous large-scale clinical trials on patients with ventilator-associated pneumonia or gram-negative sepsis, showed that addition of clarithromycin to standard antibiotic therapy conferred a significant survival benefit in the subgroup of patients with respiratory dysfunction and MODS. The INCLASS study is aiming to assess the efficacy of intravenous treatment of clarithromycin in the reduction of 28-day mortality among patients suffering from these entities.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hellenic Institute for the Study of Sepsis
• Collaborator: European Commission
• Treatments: Clarithromycin

Criteria

Inclusion Criteria:

• Adult patients (≥18 years)

• Patients of both genders

• Informed consent form signed by patient or by first-degree relative in case of patient unable to consent

• Negative (blood or urinary) pregnancy test for female patients of reproductive age

• Willingness to receive contraception during and seven days after the administration of the study drug.

• Presence of one or more of the following infections: hospital-acquired pneumonia (HAP), health-care associated pneumonia (HCAP), ventilator-associated pneumonia (VAP), primary Gram-negative bacteremia and intra-abdominal infections.

• Presence of sepsis as defined by: Sequential Organ Failure Assessment (SOFA) score of 2 or more points for patients who are admitted with infection at the emergency department or increase of admission SOFA score by 2 or more points consequent to infection, for patients already hospitalized

• Respiratory dysfunction defined as one Partial Arterial Oxygen Pressure to Fraction of Inspired Oxygen (PaO2/FiO2) ratio inferior to 200, independently of the Positive End Expiratory Pressure (PEEP) level.

• Total SOFA points for organ dysfunctions other than the respiratory function more than 3

Exclusion Criteria:

• Denial for informed consent

• Age inferior to 18 years

• Pregnancy (confirmed by blood or urinary pregnancy test) or lactation for female patients of reproductive age.

• Unwillingness to receive contraception during and seven days after the administration of the study drug.

• HIV infection (with known Cluster of Differentiation 4-positive [CD4] cell count ≤ 200/mm3)

• Solid organ, or bone marrow transplantation

• Corticosteroid oral or intravenous intake greater than 0.4 mg/kg of equivalent prednisone daily over the last 15 days

• Known active neoplasms compromising short-term survival (1 month)

• Neutropenia <1000/mm3

• Known allergy to macrolides

• Previous participation in the study

• Administration of a macrolide for the current infection