Procalcitonin-guided initiation of antibiotics in AECOPD inpatients: study protocol for a multicenter randomised controlled trial

Lixue Huang, Jinxiang Wang, Xiaoying Gu, Weili Sheng, Yeming Wang, Bin Cao, Lixue Huang, Jinxiang Wang, Xiaoying Gu, Weili Sheng, Yeming Wang, Bin Cao

Abstract

Introduction: Current antibiotic prescription for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is generally based on the Anthonisen criteria in The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guideline that have a potential risk of antibiotics overuse. The dilemma is to identify patients who are most likely to benefit from antibiotics while avoiding unnecessary antibiotic use. Procalcitonin (PCT), a more sensitive and specific biomarker of bacterial infection than other conventional laboratory tests, has the potential to determine those patients in whom antibiotics would be beneficial. It is unclear whether PCT-guided antibiotic therapy is safe and effective for patients hospitalised with AECOPD. The study hypothesis is that PCT-guided antibiotic therapy could reduce the antibiotic prescription rate for AECOPD, compared with the GOLD guideline recommendations, without negatively impacting the treatment success rate.

Methods and analysis: In this multicenter, open-label, randomised controlled trial, we aim to enrol 500 hospitalised patients with AECOPD that will be randomly assigned to either a PCT-guided group or a GOLD guideline-guided group. The coprimary endpoints are antibiotic prescription rate for AECOPD within 30 days post randomisation and treatment success rate at day 30 post randomisation. The secondary outcomes include: antibiotic prescription rate at day 1 post randomisation; hospital antibiotic exposure; length of hospital stay; rate of subsequent exacerbation and hospital readmission; overall mortality within 30 days post randomisation; changes in lung function and the score of COPD assessment test and modified Medical Research Council; and rate of intensive care unit admission.

Ethics and dissemination: This trial has been approved by the ethic committee of China-Japan Friendship Hospital. The findings of the study will be disseminated in peer-reviewed journals. If the results of the study are positive, PCT-guided antibiotic therapy is likely to change the guidelines for antibiotic recommendations for patients with AECOPD.

Trial registration number: ClinicalTrials.gov: NCT04682899.

Keywords: clinical trials; primary care; protocols & guidelines; thoracic medicine.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
The flow chart of enrolled participants. AECOPD, acute exacerbation of chronic obstructive pulmonary disease; PCT, procalcitonin.

References

    1. Zhou M, Wang H, Zhu J, et al. . Cause-Specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the global burden of disease study 2013. Lancet 2016;387:251–72. 10.1016/S0140-6736(15)00551-6
    1. Zhong N, Wang C, Yao W, et al. . Prevalence of chronic obstructive pulmonary disease in China: a large, population-based survey. Am J Respir Crit Care Med 2007;176:753–60. 10.1164/rccm.200612-1749OC
    1. Wang C, Xu J, Yang L, et al. . Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet 2018;391:1706–17. 10.1016/S0140-6736(18)30841-9
    1. Global Initiative for Chronic Obstructive Lung Disease . Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. gold, 2020. Available:
    1. Lindenauer PK, Pekow P, Gao S, et al. . Quality of care for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 2006;144:894–903. 10.7326/0003-4819-144-12-200606200-00006
    1. López-Campos JL, Hartl S, Pozo-Rodriguez F, et al. . Antibiotic prescription for COPD exacerbations admitted to hospital: European COPD audit. PLoS One 2015;10:e0124374. 10.1371/journal.pone.0124374
    1. Ma Y, Huang K, Liang C, et al. . Real-World antibiotic use in treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in China: evidence from the ACURE study. Front Pharmacol 2021;12:649884. 10.3389/fphar.2021.649884
    1. Butler CC, Gillespie D, White P, et al. . C-Reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med 2019;381:111–20. 10.1056/NEJMoa1803185
    1. Anthonisen NR, Manfreda J, Warren CP, et al. . Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987;106:196–204. 10.7326/0003-4819-106-2-196
    1. Global Initiative for Chronic Obstructive Lung Disease . Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2020.
    1. Brusse-Keizer MGJ, Grotenhuis AJ, Kerstjens HAM, et al. . Relation of sputum colour to bacterial load in acute exacerbations of COPD. Respir Med 2009;103:601–6. 10.1016/j.rmed.2008.10.012
    1. Daniels JMA, de Graaff CS, Vlaspolder F, et al. . Sputum colour reported by patients is not a reliable marker of the presence of bacteria in acute exacerbations of chronic obstructive pulmonary disease. Clin Microbiol Infect 2010;16:583–8. 10.1111/j.1469-0691.2009.02892.x
    1. Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. . Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet 2004;363:600–7. 10.1016/S0140-6736(04)15591-8
    1. Kristoffersen KB, Søgaard OS, Wejse C, et al. . Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission--a randomized trial. Clin Microbiol Infect 2009;15:481–7. 10.1111/j.1469-0691.2009.02709.x
    1. Schuetz P, Christ-Crain M, Thomann R, et al. . Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009;302:1059–66. 10.1001/jama.2009.1297
    1. Stolz D, Christ-Crain M, Bingisser R, et al. . Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest 2007;131:9–19. 10.1378/chest.06-1500
    1. Wang J-X, Zhang S-M, Li X-H, et al. . Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial. Int J Infect Dis 2016;48:40–5. 10.1016/j.ijid.2016.04.024
    1. Chan A-W, Tetzlaff JM, Gøtzsche PC, et al. . Spirit 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:e7586. 10.1136/bmj.e7586
    1. Assink-de Jong E, de Lange DW, van Oers JA, et al. . Stop Antibiotics on guidance of Procalcitonin Study (SAPS): a randomised prospective multicenter investigator-initiated trial to analyse whether daily measurements of procalcitonin versus a standard-of-care approach can safely shorten antibiotic duration in intensive care unit patients--calculated sample size: 1816 patients. BMC Infect Dis 2013;13:178. 10.1186/1471-2334-13-178
    1. Chow AW, Hall CB, Klein JO, et al. . Evaluation of new anti-infective drugs for the treatment of respiratory tract infections. infectious diseases Society of America and the food and drug administration. Clin Infect Dis 1992;15 Suppl 1:S62–88. 10.1093/clind/15.supplement_1.s62
    1. Jones PW, Harding G, Berry P, et al. . Development and first validation of the COPD assessment test. Eur Respir J 2009;34:648–54. 10.1183/09031936.00102509
    1. Fletcher CM. Standardised questionnaire on respiratory symptoms: a statement prepared and Approved by the MRC Committee on the aetiology of chronic bronchitis (MRC breathlessness score). BMJ 1960;2:1662.
    1. Prins HJ, Duijkers R, Lutter R, et al. . Blood eosinophilia as a marker of early and late treatment failure in severe acute exacerbations of COPD. Respir Med 2017;131:118–24. 10.1016/j.rmed.2017.07.064
    1. Rohde GGU, Koch A, Welte T, et al. . Randomized double blind placebo-controlled study to demonstrate that antibiotics are not needed in moderate acute exacerbations of COPD--the ABACOPD study. BMC Pulm Med 2015;15:5. 10.1186/1471-2466-15-5
    1. Llor C, Moragas A, Hernández S, et al. . Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012;186:716–23. 10.1164/rccm.201206-0996OC
    1. Miravitlles M, Moragas A, Hernández S, et al. . Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest 2013;144:1571–7. 10.1378/chest.13-0518
    1. van Velzen P, Ter Riet G, Bresser P, et al. . Doxycycline for outpatient-treated acute exacerbations of COPD: a randomised double-blind placebo-controlled trial. Lancet Respir Med 2017;5:492–9. 10.1016/S2213-2600(17)30165-0
    1. Assicot M, Gendrel D, Carsin H, et al. . High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341:515–8. 10.1016/0140-6736(93)90277-N
    1. Harbarth S, Holeckova K, Froidevaux C, et al. . Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001;164:396–402. 10.1164/ajrccm.164.3.2009052
    1. Simon L, Gauvin F, Amre DK, et al. . Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 2004;39:206–17. 10.1086/421997
    1. Mathioudakis AG, Chatzimavridou-Grigoriadou V, Corlateanu A, et al. . Procalcitonin to guide antibiotic administration in COPD exacerbations: a meta-analysis. Eur Respir Rev 2017;26. 10.1183/16000617.0073-2016. [Epub ahead of print: 31 01 2017].

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