Effectiveness of antitussives, anticholinergics or honey versus usual care in adults with uncomplicated acute bronchitis: a study protocol of an open randomised clinical trial in primary care

Josep M Cots, Ana Moragas, Ana García-Sangenís, Rosa Morros, Ainhoa Gomez-Lumbreras, Dan Ouchi, Ramon Monfà, Helena Pera, Jesus Pujol, Carolina Bayona, Mariam de la Poza-Abad, Carl Llor, Josep M Cots, Ana Moragas, Ana García-Sangenís, Rosa Morros, Ainhoa Gomez-Lumbreras, Dan Ouchi, Ramon Monfà, Helena Pera, Jesus Pujol, Carolina Bayona, Mariam de la Poza-Abad, Carl Llor

Abstract

Introduction: Despite the frequent use of therapies in acute bronchitis, the evidence of their benefit is lacking, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of three symptomatic therapies (dextromethorphan, ipratropium or honey) associated with usual care and the usual care in adults with acute bronchitis.

Methods and analysis: This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than 3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, dextromethorphan 30 mg three times a day, ipratropium bromide inhaler 20 µg two puffs three times a day or honey 30 mg (a spoonful) three times a day, all taken for up to 14 days. The exclusion criteria will be pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs or admitted to a long-term residence.

Sample: 668 patients. The primary outcome will be the number of days with moderate-to-severe cough. All patients will be given a paper-based symptom diary to be self-administered. A second visit will be scheduled at day 2 or 3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called 6 weeks after the baseline visit.

Ethics and dissemination: The study has been approved by the Ethical Board of IDIAP Jordi Gol (reference number: AC18/002). The findings of this trial will be disseminated through research conferences and peer-review journals.

Trial registration number: NCT03738917; Pre-results.

Keywords: infectious diseases; respiratory infections; therapeutics.

Conflict of interest statement

Competing interests: AM and CL report receiving research grants from Abbott Diagnostics.

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study scheme. GPs, general practitioners.

References

    1. Woodhead M, Blasi F, Ewig S, et al. . Guidelines for the management of adult lower respiratory tract infections--full version. Clin Microbiol Infect 2011;17(Suppl.6):E1–59. 10.1111/j.1469-0691.2011.03672.x
    1. Macfarlane J, Holmes W, Gard P, et al. . Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community. Thorax 2001;56:109–14. 10.1136/thorax.56.2.109
    1. Albert RH. Diagnosis and treatment of acute bronchitis. Am Fam Physician 2010;82:1345–50.
    1. Tackett KL, Atkins A. Evidence-based acute bronchitis therapy. J Pharm Pract 2012;25:586–90. 10.1177/0897190012460826
    1. Chalmers JD, Hill AT. Investigation of "non-responding" presumed lower respiratory tract infection in primary care. BMJ 2011;343:d5840 10.1136/bmj.d5840
    1. Smith SM, Fahey T, Smucny J, et al. . Antibiotics for acute bronchitis. Cochrane Database Syst Rev 2017;6:CD000245 10.1002/14651858.CD000245.pub4
    1. Hamoen M, Broekhuizen BD, Little P, et al. . Medication use in European primary care patients with lower respiratory tract infection: an observational study. Br J Gen Pract 2014;64:e81–91. 10.3399/bjgp14X677130
    1. Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database Syst Rev 2014;11:CD001831 10.1002/14651858.CD001831.pub5
    1. Morice A, Abdul-Manap R. Drug treatments for coughs and colds. Prescriber 1998;9:74–9.
    1. Llor C, Moragas A, Bayona C, et al. . Efficacy of anti-inflammatory or antibiotic treatment in patients with non-complicated acute bronchitis and discoloured sputum: randomised placebo controlled trial. BMJ 2013;347:f5762 10.1136/bmj.f5762
    1. Little P, Moore M, Kelly J, et al. . Ibuprofen, paracetamol, and steam for patients with respiratory tract infections in primary care: pragmatic randomised factorial trial. BMJ 2013;347:f6041 10.1136/bmj.f6041
    1. El-Gohary M, Hay AD, Coventry P, et al. . Corticosteroids for acute and subacute cough following respiratory tract infection: a systematic review. Fam Pract 2013;30:492–500. 10.1093/fampra/cmt034
    1. Björnsdóttir I, Einarson TR, Gudmundsson LS, et al. . Efficacy of diphenhydramine against cough in humans: a review. Pharm World Sci 2007;29:577–83. 10.1007/s11096-007-9122-2
    1. Yale SH, Liu K. Echinacea purpurea therapy for the treatment of the common cold: a randomized, double-blind, placebo-controlled clinical trial. Arch Intern Med 2004;164:1237–41. 10.1001/archinte.164.11.1237
    1. Timmer A, Günther J, Motschall E, et al. . Pelargonium sidoides extract for treating acute respiratory tract infections. Cochrane Database Syst Rev 2013;10:CD006323 10.1002/14651858.CD006323.pub3
    1. Jiang L, Li K, Wu T. Chinese medicinal herbs for acute bronchitis. Cochrane Database Syst Rev 2012;2:CD004560 10.1002/14651858.CD004560.pub4
    1. Holzinger F, Chenot JF. Systematic review of clinical trials assessing the effectiveness of ivy leaf (hedera helix) for acute upper respiratory tract infections. Evid Based Complement Alternat Med 2011;2011:1–9. 10.1155/2011/382789
    1. Parvez L, Vaidya M, Sakhardande A, et al. . Evaluation of antitussive agents in man. Pulm Pharmacol 1996;9:299–308. 10.1006/pulp.1996.0039
    1. Pavesi L, Subburaj S, Porter-Shaw K. Application and validation of a computerized cough acquisition system for objective monitoring of acute cough: a meta-analysis. Chest 2001;120:1121–8. 10.1378/chest.120.4.1121
    1. Freestone C, Eccles R. Assessment of the antitussive efficacy of codeine in cough associated with common cold. J Pharm Pharmacol 1997;49:1045–9. 10.1111/j.2042-7158.1997.tb06039.x
    1. Paul IM, Yoder KE, Crowell KR, et al. . Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents. Pediatrics 2004;114:e85–e90. 10.1542/peds.114.1.e85
    1. Korppi M, Laurikainen K, Pietikäinen M, et al. . Antitussives in the treatment of acute transient cough in children. Acta Paediatr Scand 1991;80:969–71. 10.1111/j.1651-2227.1991.tb11764.x
    1. Braman SS. Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice guidelines. Chest 2006;129:95S–103. 10.1378/chest.129.1_suppl.95S
    1. Melbye H, Kongerud J, Vorland L. Reversible airflow limitation in adults with respiratory infection. Eur Respir J 1994;7:1239–45. 10.1183/09031936.94.07071239
    1. Becker LA, Hom J, Villasis-Keever M, et al. . Beta2-agonists for acute cough or a clinical diagnosis of acute bronchitis. Cochrane Database Syst Rev 2015;9:CD001726.
    1. Melbye H, Aasebø U, Straume B. Symptomatic effect of inhaled fenoterol in acute bronchitis: a placebo-controlled double-blind study. Fam Pract 1991;8:216–22. 10.1093/fampra/8.3.216
    1. Higenbottam TW. Anticholinergics and cough. Postgrad Med J 1987;63(Suppl 1):75–8.
    1. Zanasi A, Lecchi M, Del Forno M, et al. . A randomized, placebo-controlled, double-blind trial on the management of post-infective cough by inhaled ipratropium and salbutamol administered in combination. Pulm Pharmacol Ther 2014;29:224–32. 10.1016/j.pupt.2014.07.008
    1. Coulson FR, Fryer AD. Muscarinic acetylcholine receptors and airway diseases. Pharmacol Ther 2003;98:59–69. 10.1016/S0163-7258(03)00004-4
    1. Wang K, Birring SS, Taylor K, et al. . Montelukast for postinfectious cough in adults: a double-blind randomised placebo-controlled trial. Lancet Respir Med 2014;2:35–43. 10.1016/S2213-2600(13)70245-5
    1. Cayley WE. Beta2 Agonists for Acute Cough or a Clinical Diagnosis of Acute Bronchitis. Am Fam Physician 2017;95:551.
    1. Oduwole O, Udoh EE, Oyo-Ita A, et al. . Honey for acute cough in children. Cochrane Database Syst Rev 2018;4:CD007094 10.1002/14651858.CD007094.pub5
    1. Khan RU, Naz S, Abudabos AM. Towards a better understanding of the therapeutic applications and corresponding mechanisms of action of honey. Environ Sci Pollut Res Int 2017;24:27755–66. 10.1007/s11356-017-0567-0
    1. Lusby PE, Coombes AL, Wilkinson JM. Bactericidal activity of different honeys against pathogenic bacteria. Arch Med Res 2005;36:464–7. 10.1016/j.arcmed.2005.03.038
    1. de la Poza Abad M, Mas Dalmau G, Moreno Bakedano M, et al. . Prescription Strategies in Acute Uncomplicated Respiratory Infections: A Randomized Clinical Trial. JAMA Intern Med 2016;176:21–9. 10.1001/jamainternmed.2015.7088
    1. de la Poza Abad M, Mas Dalmau G, Moreno Bakedano M, et al. . Rationale, design and organization of the delayed antibiotic prescription (DAP) trial: a randomized controlled trial of the efficacy and safety of delayed antibiotic prescribing strategies in the non-complicated acute respiratory tract infections in general practice. BMC Fam Pract 2013;14:63 10.1186/1471-2296-14-63

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