Lancet Respir Med

Addition of clarithromycin to CAP therapy validated in randomized trial

January 16, 2024

Adding clarithromycin to standard of care enhanced early clinical response and attenuated the inflammatory response in patients hospitalized with CAP.

• The phase 3 double-blind, randomized ACCESS trial enrolled hospitalized adults with CAP who had systemic inflammatory response syndrome, Sequential Organ Failure Assessment (SOFA) score ≥2, and procalcitonin ≥0.25 ng/mL. Participants were randomly assigned (1:1) to standard of care medication (including IV third-generation cephalosporin or IV β-lactam plus β-lactamase inhibitor combo) plus either oral placebo or oral clarithromycin 500 mg bid for 7 days. Primary composite endpoint required that patients fulfilled both of the following conditions after 72 hours: (1) decrease in respiratory symptom severity score of ≥50% as an indicator of early clinical response and (2) decrease in SOFA score of ≥30% or favorable procalcitonin kinetics (defined as ≥80% decrease from baseline or procalcitonin <0.25 ng/mL), or both, as an indicator of early inflammatory response.
• A total of 278 individuals were randomly allocated to receive standard of care in combination with either clarithromycin (n=139) or placebo (n=139). Of those, 134 patients in the clarithromycin group (five withdrew consent) and 133 patients in the placebo group (six withdrew consent) were included in the primary endpoint analysis. Primary endpoint was met in 68% of patients in the clarithromycin group vs. 38% of patients in the placebo group (odds ratio [OR], 3.40; 95% confidence interval [CI], 2.06-5.63; p<0·0001). Serious treatment-emergent adverse events (TEAEs) occurred in 43% of patients in the clarithromycin group and 53% of patients in the placebo group (OR 1.46; 95% CI, 0.89-2.35; p=0·14). None of the serious TEAEs were deemed to be related to treatment assignment.
• The findings suggest the importance of adding clarithromycin to β-lactams for treatment of inpatients with CAP to achieve early clinical response and early dampening of the inflammatory burden.

Source:

Giamarellos-Bourboulis EJ, et al. (2024, January 3). Lancet Respir Med. Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial. https://pubmed.ncbi.nlm.nih.gov/38184008/