Anti-inflammatory Action of Oral Clarithromycin in Community-acquired Pneumonia

• Status: Recruiting
• Trial end date: 2023-04-20
• Target enrollment: 0
• Participant gender: All

Summary

Traditional management of community-acquired pneumonia (CAP) relies on the prompt administration of antimicrobials that target the most common causative pathogens. Retrospective analysis of observational clinical studies in CAP showed that the addition of macrolides to standard antibiotic therapy conferred a significant survival benefit. The proposed benefit of macrolides is coming from their anti-inflammatory mode of action. An RCT that proves the attenuation of the high inflammatory burden of the host with CAP after addition of clarithromycin in the treatment regimen is missing. This RCT is aiming to prove that addition of oral clarithromycin to a β-lactam rapidly attenuates the high inflammatory burden of the host in CAP.

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

Details

• Lead Sponsor: Hellenic Institute for the Study of Sepsis
• Treatments: Ceftriaxone; Clarithromycin; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination

Criteria

Inclusion Criteria:

• Adult patients (≥18 years)

• Male of female gender

• In case of non-menopausal women, unwillingness to become pregnant during the study period. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study.

• Written informed consent provided by the patients or by a first-degree relative in case of patients unable to consent

• Presence of at least two signs of SIRS (see below for definition)

• SOFA score ≥2 (see Appendix I)

• PCT ≥0.25 ng/ml

• Presence of at least two of the following signs: i) cough; ii) purulent sputum expectoration; iii) dyspnea; and/or iv) pleuritic chest pain

• Presence of CAP (see below for definition)

SIRS is defined by the presence of at least two of the following criteria:

• Core temperature >38 Celsius degrees or <36 Celsius degrees

• Heart rate >90 beats/minute

• Breath rate >20 breaths/minute or pco2<32 mmHg

• Total white blood cell count >12,000/mm3 or <4,000/mm3 or >15% bands

CAP is defined as the presence of auscultatory findings compatible with CAP and new consolidation in chest X-ray in a patient without any history of contact with the hospital environment or with health-care facilities the last 90 days.

Exclusion Criteria:

• Age below 18 years

• Denial of written informed consent

• Presence of infection by SARS-CoV-2 (COVID-19)

• Intake of any macrolide for the current episode of CAP under study

• Oral or intravenous intake of corticosteroids defined as any more than 0.4mg/kg daily intake of equivalent prednisone for the last 15 days

• Neutropenia defined as an absolute neutrophil count below 1,000/mm3

• Known infection by the human immunodeficiency virus

• Any chronic anti-cytokine treatment (e.g. antibodies against TNF for rheumatoid arthritis)

• Hospitalization for more than 2 days the last 90 days

• QTc interval at rest ECG ≥500 msec or history of known congenital long QT syndrome

• Concomitant administration with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4, (lovastatin or simvastatin), and presence of any contraindications for the study drug

• Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study.