Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial
Year: 2022
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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.
Source: Critical Care
Authors: Eleni Karakike, Brendon P. Scicluna, Maria Roumpoutsou, Ioannis Mitrou, Niki Karampela, Athanasios Karageorgos, Konstantinos Psaroulis, Eleni Massa, Achillefs Pitsoulis, Panagiotis Chaloulis, Evanthia Pappa, Irene T. Schrijver, Frantzeska Frantzeskaki, Malvina Lada, Nicolas Dauby, David De Bels, Ioannis Floros, Souzana Anisoglou, Eleni Antoniadou, Maria Patrani, Glykeria Vlachogianni, Eleni Mouloudi, Anastasia Antoniadou, David Grimaldi, Thierry Roger, W. Joost Wiersinga, Iraklis Tsangaris, Evangelos J. Giamarellos-Bourboulis
Institutions: National and Kapodistrian University of Athens, University of Malta, Mater Dei Hospital, Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Hippocration General Hospital, Theageneio General Hospital, Laiko General Hospital of Athens, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Sismanoglio General Hospital, Université Libre de Bruxelles, Centre Hospitalier Universitaire de Saint-Pierre, Centre Hospitalier Universitaire Brugmann
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,690
Award: G8609360947
OpenAlex ID: W4283069360