Attenuation of the high inflammatory burden in Community-Aquired Pneumonia (CAP) MedDRA version: 20.0 Level: PT Classification code 10035664 Term: Pneumonia System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Klaricid
Product Name: Clarithromycin
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Hellenic Institute for the Study of Sepsis
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age =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 • SOFA score =2 • 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 93 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 185
Exclusion criteria
Exclusion criteria: • Age below 18 years • Denial of written informed consent • 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) • Infection by the SARS-CoV-2 virus • 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 drugs • Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Based on evidence coming from observational studies that addition of macrolides in the treatment regimen of CAP exhibits some anti-inflammatory mode of action, this RCT is aiming to prove that addition of oral clarithromycin to a ß-lactam rapidly attenuates the high inflammatory burden of the host in CAP. ;Secondary Objective: Not applicable;Primary end point(s): This is defined on day 4 and it is a composite endpoint. This endpoint is composed by two conditions A and B. Condition A is: the sum of scoring for the symptoms of cough, dyspnea, purulent sputum expectoration and pleuritic chest pain on visit 4 is decreased by at least 50% from the baseline score of day 1 without the development of any new symptom Condition B is: The SOFA score on visit 4 is decreased by at least 30% from the baseline SOFA score of day 1 and/or serum PCT on visit 4 has decreased by at least 80% from baseline PCT on screening or it is below 0.25 ng/ml;Timepoint(s) of evaluation of this end point: Screening visit Day 1 Day 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Mortality after 28 and 90 days • Clinical success at the EOT visit • Development of new organ dysfunctions until day 90 • New sepsis episode and time to new sepsis episode until day 90 • Hospital discharge until day 90 • Hospital readmission until day 90 • Achievement of more than 50% decrease of baseline SOFA score at EOT visit • Change of function of monocytes, Th1, Th2 and T17 cells • Change of gene expression of anti-inflammatory genes • Change of key gene expression of the cholesterol homeostasis pathway namely genes MVK, SC5D, MVD, STARD4 and SQLE • Anti-inflammatory PCT change • Change of the IL-10/TNFa ratio and of circulating IL-6/IL-8 • Epidemiology of pathogens of CAP for patients with at least two signs of SIRS The above endpoints will also be analyzed separately for patients infected or colonized by clarithromycin-susceptible and clarithromycin-resistant S.pneumoniae;Timepoint(s) of evaluation of this end point: Day 1 Day 8 Day 28 Day 90 | — |
Countries
Greece
Contacts
Public ContactPresident of the Board
Hellenic Institute for the Study of Sepsis
Outcome results
None listed