Glucocorticoids Versus Placebo for the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Summary

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with a poor prognosis, with a 3-month mortality rate of over 50%. To date, no treatment has been proven to be effective in AI-FPI. The interest of glucocorticoids is controversial and needs to be confirmed. This confirmation is mandatory to validate the improvement of the prognosis of EA-IPF under this treatment but also to search for unsuspected deleterious effects as it has been shown with immunosuppressants in stable idiopathic pulmonary fibrosis.

Timeline

Start

2023-10-26

Primary completion

2026-03-30

Completion

2026-12-31

Publications

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• Background Naccache JM, Jouneau S, Didier M, Borie R, Cachanado M, Bourdin A, Reynaud-Gaubert M, Bonniaud P, Israel-Biet D, Prevot G, Hirschi S, Lebargy F, Marchand-Adam S, Bautin N, Traclet J, Gomez E, Leroy S, Gagnadoux F, Riviere F, Bergot E, Gondouin A, Blanchard E, Parrot A, Blanc FX, Chabrol A, Dominique S, Gibelin A, Tazi A, Berard L, Brillet PY, Debray MP, Rousseau A, Kerjouan M, Freynet O, Dombret MC, Gamez AS, Nieves A, Beltramo G, Pastre J, Le Borgne-Krams A, Degot T, Launois C, Plantier L, Wemeau-Stervinou L, Cadranel J, Chenivesse C, Valeyre D, Crestani B, Cottin V, Simon T, Nunes H; EXAFIP investigators and the OrphaLung network. Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022 Jan;10(1):26-34. doi: 10.1016/S2213-2600(21)00354-4. Epub 2021 Sep 7.
• Background Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, Behr J, Cottin V, Danoff SK, Morell F, Flaherty KR, Wells A, Martinez FJ, Azuma A, Bice TJ, Bouros D, Brown KK, Collard HR, Duggal A, Galvin L, Inoue Y, Jenkins RG, Johkoh T, Kazerooni EA, Kitaichi M, Knight SL, Mansour G, Nicholson AG, Pipavath SNJ, Buendia-Roldan I, Selman M, Travis WD, Walsh S, Wilson KC; American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68. doi: 10.1164/rccm.201807-1255ST.
• Background Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, Lee JS, Maher TM, Wells AU, Antoniou KM, Behr J, Brown KK, Cottin V, Flaherty KR, Fukuoka J, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kolb M, Lynch DA, Myers JL, Raghu G, Richeldi L, Taniguchi H, Martinez FJ. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. Am J Respir Crit Care Med. 2016 Aug 1;194(3):265-75. doi: 10.1164/rccm.201604-0801CI.
• Background Kondoh Y, Azuma A, Inoue Y, Ogura T, Sakamoto S, Tsushima K, Johkoh T, Fujimoto K, Ichikado K, Matsuzawa Y, Saito T, Kishi K, Tomii K, Sakamoto N, Aoshima M, Araya J, Izumi S, Arita M, Abe M, Yamauchi H, Shindoh J, Suda T, Okamoto M, Ebina M, Yamada Y, Tohda Y, Kawamura T, Taguchi Y, Ishii H, Hashimoto N, Abe S, Taniguchi H, Tagawa J, Bessho K, Yamamori N, Homma S. Thrombomodulin Alfa for Acute Exacerbation of Idiopathic Pulmonary Fibrosis. A Randomized, Double-Blind Placebo-controlled Trial. Am J Respir Crit Care Med. 2020 May 1;201(9):1110-1119. doi: 10.1164/rccm.201909-1818OC.
• Background Papiris SA, Kagouridis K, Kolilekas L, Papaioannou AI, Roussou A, Triantafillidou C, Baou K, Malagari K, Argentos S, Kotanidou A, Karakatsani A, Manali ED. Survival in Idiopathic pulmonary fibrosis acute exacerbations: the non-steroid approach. BMC Pulm Med. 2015 Dec 14;15:162. doi: 10.1186/s12890-015-0146-4.
• Background Farrand E, Vittinghoff E, Ley B, Butte AJ, Collard HR. Corticosteroid use is not associated with improved outcomes in acute exacerbation of IPF. Respirology. 2020 Jun;25(6):629-635. doi: 10.1111/resp.13753. Epub 2019 Dec 17.
• Background Nalysnyk L, Cid-Ruzafa J, Rotella P, Esser D. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev. 2012 Dec 1;21(126):355-61. doi: 10.1183/09059180.00002512.
• Background Duchemann B, Annesi-Maesano I, Jacobe de Naurois C, Sanyal S, Brillet PY, Brauner M, Kambouchner M, Huynh S, Naccache JM, Borie R, Piquet J, Mekinian A, Virally J, Uzunhan Y, Cadranel J, Crestani B, Fain O, Lhote F, Dhote R, Saidenberg-Kermanac'h N, Rosental PA, Valeyre D, Nunes H. Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris. Eur Respir J. 2017 Aug 3;50(2):1602419. doi: 10.1183/13993003.02419-2016. Print 2017 Aug.
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• Background Idiopathic Pulmonary Fibrosis Clinical Research Network; Raghu G, Anstrom KJ, King TE Jr, Lasky JA, Martinez FJ. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012 May 24;366(21):1968-77. doi: 10.1056/NEJMoa1113354. Epub 2012 May 20.
• Background Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE Jr, Lasky JA, Loyd JE, Noth I, Olman MA, Raghu G, Roman J, Ryu JH, Zisman DA, Hunninghake GW, Colby TV, Egan JJ, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kondoh Y, Lynch DA, Muller-Quernheim J, Myers JL, Nicholson AG, Selman M, Toews GB, Wells AU, Martinez FJ; Idiopathic Pulmonary Fibrosis Clinical Research Network Investigators. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007 Oct 1;176(7):636-43. doi: 10.1164/rccm.200703-463PP. Epub 2007 Jun 21.
• Background Collard HR, Yow E, Richeldi L, Anstrom KJ, Glazer C; IPFnet investigators. Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials. Respir Res. 2013 Jul 13;14(1):73. doi: 10.1186/1465-9921-14-73.
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• Background Parambil JG, Myers JL, Ryu JH. Histopathologic features and outcome of patients with acute exacerbation of idiopathic pulmonary fibrosis undergoing surgical lung biopsy. Chest. 2005 Nov;128(5):3310-5. doi: 10.1378/chest.128.5.3310.
• Background Oda K, Ishimoto H, Yamada S, Kushima H, Ishii H, Imanaga T, Harada T, Ishimatsu Y, Matsumoto N, Naito K, Yatera K, Nakazato M, Kadota J, Watanabe K, Kohno S, Mukae H. Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis. Respir Res. 2014 Sep 1;15(1):109. doi: 10.1186/s12931-014-0109-y.
• Background Dotan Y, Vaidy A, Shapiro WB, Zhao H, Dass C, Toyoda Y, Marchetti N, Shenoy K, Cordova FC, Criner GJ, Mamary AJ. Effect of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplantation Outcome. Chest. 2018 Oct;154(4):818-826. doi: 10.1016/j.chest.2018.06.027. Epub 2018 Jun 30.
• Background Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schunemann HJ; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824. doi: 10.1164/rccm.2009-040GL.
• Background Kreuter M, Polke M, Walsh SLF, Krisam J, Collard HR, Chaudhuri N, Avdeev S, Behr J, Calligaro G, Corte T, Flaherty K, Funke-Chambour M, Kolb M, Kondoh Y, Maher TM, Molina Molina M, Morais A, Moor CC, Morisset J, Pereira C, Quadrelli S, Selman M, Tzouvelekis A, Valenzuela C, Vancheri C, Vicens-Zygmunt V, Walscher J, Wuyts W, Wijsenbeek M, Cottin V, Bendstrup E. Acute exacerbation of idiopathic pulmonary fibrosis: international survey and call for harmonisation. Eur Respir J. 2020 Apr 3;55(4):1901760. doi: 10.1183/13993003.01760-2019. Print 2020 Apr.
• Background Molyneaux PL, Cox MJ, Willis-Owen SA, Mallia P, Russell KE, Russell AM, Murphy E, Johnston SL, Schwartz DA, Wells AU, Cookson WO, Maher TM, Moffatt MF. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2014 Oct 15;190(8):906-13. doi: 10.1164/rccm.201403-0541OC.
• Background O'Dwyer DN, Ashley SL, Gurczynski SJ, Xia M, Wilke C, Falkowski NR, Norman KC, Arnold KB, Huffnagle GB, Salisbury ML, Han MK, Flaherty KR, White ES, Martinez FJ, Erb-Downward JR, Murray S, Moore BB, Dickson RP. Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in Pulmonary Fibrosis. Am J Respir Crit Care Med. 2019 May 1;199(9):1127-1138. doi: 10.1164/rccm.201809-1650OC.
• Background Cottin V, Cadranel J, Crestani B, Dalphin JC, Delaval P, Israel-Biet D, Kessler R, Reynaud-Gaubert M, Valeyre D, Wallaert B, Bouquillon B, Cordier JF. Management of idiopathic pulmonary fibrosis in France: a survey of 1244 pulmonologists. Respir Med. 2014 Jan;108(1):195-202. doi: 10.1016/j.rmed.2013.11.017. Epub 2013 Dec 3.
• Background Shulgina L, Cahn AP, Chilvers ER, Parfrey H, Clark AB, Wilson EC, Twentyman OP, Davison AG, Curtin JJ, Crawford MB, Wilson AM. Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial. Thorax. 2013 Feb;68(2):155-62. doi: 10.1136/thoraxjnl-2012-202403. Epub 2012 Nov 10.

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