Colistin Methanesulfonate Sodium Inhalation for Prophylaxis of Ventilator-Associated Pneumonia (CIVAP): A Prospective, Multicentre, Double-Blind, Randomized, Placebo-Controlled Trial

Summary

Previous studies have identified Acinetobacter baumannii (AB), Pseudomonas aeruginosa (PA), and Klebsiella pneumoniae (KP) as the predominant pathogens responsible for ventilator-associated pneumonia (VAP). The challenge of drug resistance, especially against carbapenem is intensifying, with variations noted across different regions. Multidrug-resistant organisms associated VAP (MDR-VAP) are increasing in frequency and are associated with significant morbidity, mortality, therefore imposes a heavy burden on the healthcare system. Colistin methanesulfonate sodium (CMS) has shown effectiveness against gram-negative bacteria, including carbapenem-resistant organisms (CRO) such as carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Klebsiella pneumoniae (CRKP). This trial aims to evaluate the efficacy of a 3-day course of inhaled CMS in lowering the incidence of VAP among patients undergoing invasive mechanical ventilation for at least two days and at high risk of MDR-VAP.

Timeline

Start

2025-07-15

Primary completion

2026-09

Completion

2026-12

Publications

• Background Wu Z, Zhang S, Cao Y, Wang Q, Sun K, Zheng X. Comparison of the clinical efficacy and toxicity of nebulized polymyxin monotherapy and combined intravenous and nebulized polymyxin for the treatment of ventilator-associated pneumonia caused by carbapenem-resistant gram-negative bacteria: a retrospective cohort study. Front Pharmacol. 2023 Aug 16;14:1209063. doi: 10.3389/fphar.2023.1209063. eCollection 2023.
• Background Povoa FCC, Cardinal-Fernandez P, Maia IS, Reboredo MM, Pinheiro BV. Effect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: A systematic review and meta-analysis. J Crit Care. 2018 Feb;43:240-245. doi: 10.1016/j.jcrc.2017.09.019. Epub 2017 Sep 18.
• Background Lu Q, Luo R, Bodin L, Yang J, Zahr N, Aubry A, Golmard JL, Rouby JJ; Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology. 2012 Dec;117(6):1335-47. doi: 10.1097/ALN.0b013e31827515de.
• Background Biswas S, Brunel JM, Dubus JC, Reynaud-Gaubert M, Rolain JM. Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti Infect Ther. 2012 Aug;10(8):917-34. doi: 10.1586/eri.12.78.
• Background Yu Z, Qin W, Lin J, Fang S, Qiu J. Antibacterial mechanisms of polymyxin and bacterial resistance. Biomed Res Int. 2015;2015:679109. doi: 10.1155/2015/679109. Epub 2015 Jan 15.
• Background Zhang X, Cui X, Jiang M, Huang S, Yang M. Nebulized colistin as the adjunctive treatment for ventilator-associated pneumonia: A systematic review and meta-analysis. J Crit Care. 2023 Oct;77:154315. doi: 10.1016/j.jcrc.2023.154315. Epub 2023 Apr 28.
• Background Hu JN, Hu SQ, Li ZL, Bao C, Liu Q, Liu C, Xu SY. Risk factors of multidrug-resistant bacteria infection in patients with ventilator-associated pneumonia: A systematic review and meta-analysis. J Infect Chemother. 2023 Oct;29(10):942-947. doi: 10.1016/j.jiac.2023.06.008. Epub 2023 Jun 13.
• Background Ranzani OT, Niederman MS, Torres A. Ventilator-associated pneumonia. Intensive Care Med. 2022 Sep;48(9):1222-1226. doi: 10.1007/s00134-022-06773-3. Epub 2022 Jun 30. No abstract available.
• Background Xie J, Yang Y, Huang Y, Kang Y, Xu Y, Ma X, Wang X, Liu J, Wu D, Tang Y, Qin B, Guan X, Li J, Yu K, Liu D, Yan J, Qiu H. The Current Epidemiological Landscape of Ventilator-associated Pneumonia in the Intensive Care Unit: A Multicenter Prospective Observational Study in China. Clin Infect Dis. 2018 Nov 13;67(suppl_2):S153-S161. doi: 10.1093/cid/ciy692.
• Background Ding X, Ma X, Gao S, Su L, Shan G, Hu Y, Chen J, Ma D, Zhang F, Zhu W, Sun G, Meng X, Ma L, Zhou X, Liu D, Du B; China National Critical Care Quality Control Center Group. Effect of ICU quality control indicators on VAP incidence rate and mortality: a retrospective study of 1267 hospitals in China. Crit Care. 2022 Dec 29;26(1):405. doi: 10.1186/s13054-022-04285-6.
• Background Ehrmann S, Barbier F, Demiselle J, Quenot JP, Herbrecht JE, Roux D, Lacherade JC, Landais M, Seguin P, Schnell D, Veinstein A, Gouin P, Lasocki S, Lu Q, Beduneau G, Ferrandiere M, Plantefeve G, Dahyot-Fizelier C, Chebib N, Mercier E, Heuze-Vourc'h N, Respaud R, Gregoire N, Garot D, Nay MA, Meziani F, Andreu P, Clere-Jehl R, Zucman N, Azais MA, Saint-Martin M, Gandonniere CS, Benzekri D, Merdji H, Tavernier E; Reva and CRICS-TRIGGERSEP F-CRIN Research Networks. Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia. N Engl J Med. 2023 Nov 30;389(22):2052-2062. doi: 10.1056/NEJMoa2310307. Epub 2023 Oct 25.
• Background Papazian L, Klompas M, Luyt CE. Ventilator-associated pneumonia in adults: a narrative review. Intensive Care Med. 2020 May;46(5):888-906. doi: 10.1007/s00134-020-05980-0. Epub 2020 Mar 10.
• Background Metersky ML, Kalil AC. Management of Ventilator-Associated Pneumonia: Guidelines. Infect Dis Clin North Am. 2024 Mar;38(1):87-101. doi: 10.1016/j.idc.2023.12.004.

Drugs

Indications

No indication recorded.