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- Title
Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial.
- Authors
Karakike, Eleni; Scicluna, Brendon P.; Roumpoutsou, Maria; Mitrou, Ioannis; Karampela, Niki; Karageorgos, Athanasios; Psaroulis, Konstantinos; Massa, Eleni; Pitsoulis, Achillefs; Chaloulis, Panagiotis; Pappa, Evanthia; Schrijver, Irene T.; Frantzeskaki, Frantzeska; Lada, Malvina; Dauby, Nicolas; De Bels, David; Floros, Ioannis; Anisoglou, Souzana; Antoniadou, Eleni; Patrani, Maria
- Abstract
Background: Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. Methods: We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. Results: Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) − 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35–3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06–0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. Conclusions: Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.
- Publication
Critical Care, 2022, Vol 26, Issue 1, p1
- ISSN
1364-8535
- Publication type
Article
- DOI
10.1186/s13054-022-04055-4