Benefit of Clarithromycin in Patients With Severe Infections Through Modulation of the Immune System (INCLASS)
Sepsis, Pneumonia, Gram-Negative Bacteria Infection
About this trial
This is an interventional treatment trial for Sepsis focused on measuring Macrolides
Eligibility 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
Sites / Locations
- Intensive Care Unit, Saint-Pierre University Hospital
- Intensive Care Unit, Brugmann University Hospital
- Intensive Care Unit, Erasme University Hospital
- Intensive Care Unit, Korgialeneio-Benakeio General Hospital
- Intensive Care Unit, Laikon General Hospital
- 2nd Department of Intensive Care Medicine, Attikon University Hospital
- 4th Department of Internal Medicine, Attikon University Hospital
- 2nd Department of Internal Medicine, Sismanogleio General Hospital
- Intensive Care Unit, Agios Dimitrios General Hospital
- Intensive Care Unit, G. Gennimatas General Hospital
- Intensive Care Unit, Theageneio Oncological Hospital
- Intensive Care Unit, Ippokrateion General Hospital
Arms of the Study
Arm 1
Arm 2
Placebo Comparator
Active Comparator
Placebo
Clarithromycin
After enrollment, the placebo arm will receive water for injection at a volume of 20ml diluted to a final volume of 250 ml dextrose in water 5%, infused once daily through intravenous route, within 1 hour, for a duration of four consecutive days.
After enrollment, the active drug arm will receive 1g of clarithromycin (500 mg powder for concentrate for solution for infusion per vial), dissolved into 20 ml water for injection and then diluted to a final volume of 250 ml dextrose in water 5%. This will be infused through intravenous route, once daily within 1 hour, for a duration of four consecutive days.