The goal of this clinical trial is to assess whether clarithromycin, given as an adjunct to standard-of-care antibiotic therapy, can reduce the risk of new infections and secondary sepsis in adult patients hospitalized with community-acquired pneumonia (CAP), sepsis, and sepsis-induced immunoparalysis (SII). The primary objective is to evaluate the effect of clarithromycin on the incidence of new infection, including worsening or recurrence of the initial CAP episode, new infections at other sites, and secondary sepsis during the 28-day follow-up period. Secondary objectives are to investigate the impact of clarithromycin on mortality, sepsis response, type of secondary infection, time to antimicrobial escalation, hospital readmission, quality of life, cost-effectiveness, and biomarkers of sepsis-induced immunoparalysis.
Researchers will compare clarithromycin plus standard-of-care antibiotic therapy to placebo plus standard-of-care antibiotic therapy.
Participants will:
* Receive clarithromycin or placebo, administered orally or intravenously, in addition to standard-of-care antibiotic therapy for up to 7 days. * Be evaluated during treatment and follow-up through Day 28, with additional assessment of mortality, hospital readmission, and health status through Day 90.
Age equal to or above 18 years
Patients of either gender
Written informed consent provided by the patient. For patients without decision-making capacity, informed consent must be obtained from a legally designated representative following the national legislation.
Negative (blood or urinary) pregnancy test for female patients of reproductive age
Age below 18 years
Denial of written informed consent
Pregnancy (confirmed by blood or urinary pregnancy test) or lactation for female patients
Unwillingness to receive contraception during and seven days after the administration of the IMPstudy drug (for Female patients)
Parallel
Placebo
DrugThere is no other intervention in this clinical study and participation in another clinical study is an exclusion criterion.
clarithromycin
DrugThere is no other intervention in this clinical study and participation in another clinical study is an exclusion criterion.
Incidence of new infection
The incidence of new infection within 28 days following randomization, comparing intravenous or oral clarithromycin plus standard-of-care (SoC) antibiotic therapy with placebo plus SoC. The composite endpoint includes any of the following: * Worsening of the CAP episode, defined as the need to change SoC antibiotic treatment during the first 7 days. A change to moxifloxacin due to detection of atypical pathogens is not considered worsening. * Recurrence of CAP symptoms after initial improvement, requiring initiation of new treatment or a change in treatment after Day 7. * Any new infection at a non-pulmonary site during the first 28 days. * Secondary sepsis occurring between Day 8 and Day 28, defined as the onset of a new infection or recurrence of the CAP episode accompanied by an increase of at least 2 points in the total SOFA-1 score compared with the SOFA-1 score immediately before the new infection or CAP recurrence.
All-cause mortality at Day 28
Proportion of participants who die from any cause within 28 days after randomization.
All-cause mortality at Day 90
Proportion of participants who die from any cause within 90 days after randomization.
Sepsis response at Day 7
Proportion of participants achieving at least a 25% decrease in the total SOFA-1 score from the pre-treatment Day 1 score by Day 7.
Type of new sepsis episode
Characterization of new sepsis episodes according to the predominant pathogen and site of infection.
Sepsis response by SOFA-2
Proportion of participants achieving at least a 25% decrease in the total SOFA-2 score from the pre-treatment Day 1 score by Day 7.
Primary endpoint according to baseline IL-6 and IFN-γ levels
Analysis of the primary composite endpoint according to patient subgroups defined by baseline levels of IL-6 and IFN-γ.
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