{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:59:25Z","timestamp":1773280765819,"version":"3.50.1"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T00:00:00Z","timestamp":1576454400000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["32003B_160072"],"award-info":[{"award-number":["32003B_160072"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013349","name":"Lungenliga Schweiz","doi-asserted-by":"publisher","award":["2015-08"],"award-info":[{"award-number":["2015-08"]}],"id":[{"id":"10.13039\/501100013349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic obstructive pulmonary disease (COPD) is a major public health issue affecting approximately 4% to 7% of the Swiss population. According to current inpatient guidelines, systemic corticosteroids are important in the treatment of acute COPD exacerbations and should be given for 5 to 7 days. Several studies suggest that corticosteroids accelerate the recovery of FEV1 (forced expiratory volume in 1 second), enhance oxygenation, decrease the duration of hospitalization, and improve clinical outcomes. However, the additional therapeutic benefit regarding FEV1 recovery appears to be most apparent in the first 3 to 5 days. No data are available on the optimum duration of corticosteroid treatment in primary-care patients with acute COPD exacerbations. Given that many COPD patients are treated as outpatients, there is an urgent need to improve the evidence base on COPD management in this setting. The aim of this study is to investigate whether a 3-day treatment with orally administered corticosteroids is non-inferior to a 5-day treatment in acute exacerbations of COPD in a primary-care setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\/design<\/jats:title>\n                    <jats:p>\n                      This study is a prospective double-blind randomized controlled trial conducted in a primary-care setting. It is anticipated that 470 patients with acutely exacerbated COPD will be recruited. Participants are randomized to receive systemic corticosteroid treatment of 40\u2009mg prednisone daily for 5 days (conventional arm,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009235) or for 3 days followed by 2 days of placebo (experimental arm,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009235). Antibiotic treatment for 7 days is given to all patients with CRP\u2009\u2265\u200950\u2009mg\/l, those with a known diagnosis of bronchiectasis, or those presenting with Anthonisen type I exacerbation. Additional treatment after inclusion is left at the discretion of the treating general practitioner. Follow-up visits are performed on days 3 and 7, followed by telephone interviews on days 30, 90, and 180 after inclusion in the study. The primary endpoint is the time to next exacerbation during the 6-month follow-up period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The study is designed to assess whether a 3-day course of corticosteroid treatment is not inferior to the conventional 5-day treatment course in outpatients with exacerbated COPD regarding time to next exacerbation. Depending on the results, this trial may lead to a reduction in the cumulative corticosteroid dose in COPD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02386735\">NCT02386735<\/jats:ext-link>\n                      . Registered on 12 March 2015.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-019-3856-8","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T09:02:48Z","timestamp":1576486968000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Reduction of corticosteroid use in outpatient treatment of exacerbated COPD\u00a0- Study protocol for a randomized, double-blind, non-inferiority study, (The RECUT-trial)"],"prefix":"10.1186","volume":"20","author":[{"given":"Pascal","family":"Urwyler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8605-1893","authenticated-orcid":false,"given":"Maria","family":"Boesing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Abig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Cattaneo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Dieterle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Zeller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert","family":"Bachler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Markun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Senn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Merlo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Essig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Ullmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Rutishauser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mac\u00e9 M","family":"Schuurmans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg Daniel","family":"Leuppi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,16]]},"reference":[{"issue":"6","key":"3856_CR1","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1183\/09031936.00004110","volume":"36","author":"PO Bridevaux","year":"2010","unstructured":"Bridevaux PO, Probst-Hensch NM, Schindler C, Curjuric I, Felber Dietrich D, Braendli O, et al. Prevalence of airflow obstruction in smokers and never-smokers in Switzerland. Eur Respir J. 2010;36(6):1259\u201369.","journal-title":"Eur Respir J"},{"issue":"6","key":"3856_CR2","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1159\/000243162","volume":"79","author":"JD Leuppi","year":"2010","unstructured":"Leuppi JD, Miedinger D, Chhajed PN, Buess C, Schafroth S, Bucher HC, et al. Quality of spirometry in primary care for case finding of airway obstruction in smokers. Respiration. 2010;79(6):469\u201374.","journal-title":"Respiration"},{"key":"3856_CR3","first-page":"w13567","volume":"142","author":"A Jochmann","year":"2012","unstructured":"Jochmann A, Scherr A, Jochmann DC, Miedinger D, Torok SS, Chhajed PN, et al. Impact of adherence to the GOLD guidelines on symptom prevalence, lung function decline and exacerbation rate in the Swiss COPD cohort. Swiss Med Wkly. 2012;142:w13567.","journal-title":"Swiss Med Wkly"},{"key":"3856_CR4","doi-asserted-by":"publisher","unstructured":"Jochmann A, Neubauer F, Miedinger D, Schafroth S, Tamm M, Leuppi JD. General practitioner\u2019s adherence to the COPD GOLD guidelines: baseline data of the Swiss COPD Cohort Study. Swiss Med Wkly. 2010;140. https:\/\/doi.org\/10.4414\/smw.2010.13053.","DOI":"10.4414\/smw.2010.13053"},{"issue":"3","key":"3856_CR5","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/S0954-6111(99)90004-5","volume":"93","author":"M Miravitlles","year":"1999","unstructured":"Miravitlles M, Mayordomo C, Artes M, Sanchez-Agudo L, Nicolau F, Segu JL. Treatment of chronic obstructive pulmonary disease and its exacerbations in general practice. EOLO Group. Estudio Observacional de la Limitacion Obstructiva al Flujo aEreo. Respir Med. 1999;93(3):173\u20139.","journal-title":"Respir Med"},{"issue":"21","key":"3856_CR6","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1001\/jama.2013.5023","volume":"309","author":"JD Leuppi","year":"2013","unstructured":"Leuppi JD, Schuetz P, Bingisser R, Bodmer M, Briel M, Drescher T, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309(21):2223\u201331.","journal-title":"JAMA"},{"key":"3856_CR7","volume-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2019 report)","author":"Global Initiative for Chronic Obstructive Lung Disease","year":"2019","unstructured":"Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2019 report). 2019. https:\/\/goldcopd.org\/wp-content\/uploads\/2018\/11\/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf. Accessed 2 Apr 2019."},{"issue":"9177","key":"3856_CR8","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/S0140-6736(98)11326-0","volume":"354","author":"L Davies","year":"1999","unstructured":"Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet (London, England). 1999;354(9177):456\u201360.","journal-title":"Lancet (London, England)"},{"issue":"25","key":"3856_CR9","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1056\/NEJM199906243402502","volume":"340","author":"DE Niewoehner","year":"1999","unstructured":"Niewoehner DE, Erbland ML, Deupree RH, Collins D, Gross NJ, Light RW, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med. 1999;340(25):1941\u20137.","journal-title":"N Engl J Med"},{"issue":"26","key":"3856_CR10","doi-asserted-by":"publisher","first-page":"2618","DOI":"10.1056\/NEJMoa023161","volume":"348","author":"SD Aaron","year":"2003","unstructured":"Aaron SD, Vandemheen KL, Hebert P, Dales R, Stiell IG, Ahuja J, et al. Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med. 2003;348(26):2618\u201325.","journal-title":"N Engl J Med"},{"issue":"2 Pt 1","key":"3856_CR11","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1164\/ajrccm.154.2.8756814","volume":"154","author":"WH Thompson","year":"1996","unstructured":"Thompson WH, Nielson CP, Carvalho P, Charan NB, Crowley JJ. Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. Am J Respir Crit Care Med. 1996;154(2 Pt 1):407\u201312.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"3856_CR12","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/S0735-6757(96)90120-5","volume":"14","author":"MJ Bullard","year":"1996","unstructured":"Bullard MJ, Liaw SJ, Tsai YH, Min HP. Early corticosteroid use in acute exacerbations of chronic airflow obstruction. Am J Emerg Med. 1996;14(2):139\u201343.","journal-title":"Am J Emerg Med"},{"issue":"3","key":"3856_CR13","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1378\/chest.95.3.563","volume":"95","author":"CL Emerman","year":"1989","unstructured":"Emerman CL, Connors AF, Lukens TW, May ME, Effron D. A randomized controlled trial of methylprednisolone in the emergency treatment of acute exacerbations of COPD. Chest. 1989;95(3):563\u20137.","journal-title":"Chest"},{"issue":"6","key":"3856_CR14","doi-asserted-by":"publisher","first-page":"753","DOI":"10.7326\/0003-4819-92-6-753","volume":"92","author":"RK Albert","year":"1980","unstructured":"Albert RK, Martin TR, Lewis SW. Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency. Ann Intern Med. 1980;92(6):753\u20138.","journal-title":"Ann Intern Med"},{"issue":"3","key":"3856_CR15","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1378\/chest.111.3.732","volume":"111","author":"CE McEvoy","year":"1997","unstructured":"McEvoy CE, Niewoehner DE. Adverse effects of corticosteroid therapy for COPD. A critical review. Chest. 1997;111(3):732\u201343.","journal-title":"Chest"},{"issue":"5","key":"3856_CR16","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1164\/rccm.2110047","volume":"166","author":"LJ Walsh","year":"2002","unstructured":"Walsh LJ, Lewis SA, Wong CA, Cooper S, Oborne J, Cawte SA, et al. The impact of oral corticosteroid use on bone mineral density and vertebral fracture. Am J Respir Crit Care Med. 2002;166(5):691\u20135.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"3856_CR17","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1164\/ajrccm.150.1.8025735","volume":"150","author":"M Decramer","year":"1994","unstructured":"Decramer M, Lacquet LM, Fagard R, Rogiers P. Corticosteroids contribute to muscle weakness in chronic airflow obstruction. Am J Respir Crit Care Med. 1994;150(1):11\u20136.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"3856_CR18","doi-asserted-by":"publisher","first-page":"196","DOI":"10.7326\/0003-4819-106-2-196","volume":"106","author":"NR Anthonisen","year":"1987","unstructured":"Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 1987;106(2):196\u2013204.","journal-title":"Ann Intern Med"},{"issue":"5 Suppl 2","key":"3856_CR19","doi-asserted-by":"publisher","first-page":"398s","DOI":"10.1378\/chest.117.5_suppl_2.398S","volume":"117","author":"R Rodriguez-Roisin","year":"2000","unstructured":"Rodriguez-Roisin R. Toward a consensus definition for COPD exacerbations. Chest. 2000;117(5 Suppl 2):398s\u2013401s.","journal-title":"Chest"},{"key":"3856_CR20","doi-asserted-by":"publisher","DOI":"10.1002\/9781444300710","volume-title":"Sample size tables for clinical studies","author":"D Machin","year":"2008","unstructured":"Machin D, Campbell M, Tan S-B, Tan S-H. Sample size tables for clinical studies. 3rd ed. Chichester: Wiley-Blackwell; 2008.","edition":"3"},{"key":"3856_CR21","first-page":"w13109","volume":"140","author":"P Schuetz","year":"2010","unstructured":"Schuetz P, Leuppi JD, Tamm M, Briel M, Bingisser R, Durring U, et al. Short versus conventional term glucocorticoid therapy in acute exacerbation of chronic obstructive pulmonary disease - the \u201cREDUCE\u201d trial. Swiss Med Wkly. 2010;140:w13109.","journal-title":"Swiss Med Wkly"},{"key":"3856_CR22","doi-asserted-by":"crossref","unstructured":"Committee for Medicinal Products for Human Use. Committee for Medicinal Products for Human Use (CHMP) guideline on the choice of the non-inferiority margin. Stat Med. 2006;25(10):1628\u201338.","DOI":"10.1002\/sim.2584"},{"issue":"6","key":"3856_CR23","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1002\/bimj.200610373","volume":"49","author":"T Friede","year":"2007","unstructured":"Friede T, Mitchell C, Muller-Velten G. Blinded sample size reestimation in non-inferiority trials with binary endpoints. Biom J. 2007;49(6):903\u201316.","journal-title":"Biom J"},{"issue":"9589","key":"3856_CR24","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/S0140-6736(07)61377-4","volume":"370","author":"AS Buist","year":"2007","unstructured":"Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM, et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet (London, England). 2007;370(9589):741\u201350.","journal-title":"Lancet (London, England)"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-019-3856-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13063-019-3856-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-019-3856-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T20:00:21Z","timestamp":1607976021000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-019-3856-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["3856"],"URL":"https:\/\/doi.org\/10.1186\/s13063-019-3856-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.2.13106\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.13106\/v1","asserted-by":"object"}]},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"13 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethics approval to conduct this trial at the coordinating study center in Liestal was first granted by the local ethics committee for the Region of Northwestern and Central Switzerland (EKNZ, project ID 2015\u2013017) on 31 January 2015. Four amendments regarding financial compensation for recruiting GPs, structural changes of the CRFs, and the archiving of study documents were approved by the EKNZ between April 2015 and January 2017. The study was first extended from the greater Basel area to the cantons of Luzern, Aargau, Solothurn, and later to the canton of Zurich, with the approval of the cantonal ethics committee in Zurich in May 2017. Approval for an extension to the greater Innsbruck area from the ethics committee of the University of Innsbruck was given in September 2018. Furthermore, we are currently awaiting ethics approval for another extension to the canton of Bern.The trial meets the criteria and principles of the Declaration of Helsinki and is registered in the Clinicaltrials.gov database (trial registration number NCT02386735). It was registered on 12 March 2015.Informed consent to participate in the trial is obtained by the recruiting GPs from all patients prior to study entry. Each patient is informed that participation in the study is voluntary, that they may withdraw from the study at any time without giving a reason, and that withdrawal of consent will not affect their subsequent medical assistance or treatment. On the consent form, participants are asked to allow their data to be used if they choose to withdraw from the trial. Participants are also asked to allow the research team to share their personal data with regulatory authorities, when relevant. Furthermore, patients are informed on an obligatory basis that their medical records may be examined by authorized individuals other than their treating physician. All patients are covered by liability insurance for the total duration of the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"We aim to publish the results of this study in a peer-reviewed journal and do not intend to use professional writers. Since no personal data will be published, consent for publication has not been obtained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"727"}}