The Effect of Erythropoietin on Alveolar Fluid Clearance in Patients With Acute Respiratory Distress Syndrome

Summary

Acute respiratory distress syndrome (ARDS) is a common acute and critical disease in clinic. The clinical mortality is as high as 30%-40%. At present, there is no specific treatment. Erythropoietin (EPO), also known as erythrocyte- stimulating factor, erythropoietin, has a certain amount in normal human body, mainly synthesized by liver in infants and kidneys in adults, which can stimulate erythropoiesis. In recent years, more and more studies have shown that high-dose exogenous EPO administration has benefit effects on multi-organ protection. Therefore, we designed this prospective, double-blind, placebo-controlled trial for defecting EPO on the alveolar fluid clearance of ARDS. The study mainly answers the following questions: Does human erythropoietin accelerate the resolution of alveolar edema in ARDS? Is there any effect on hospital survival? The study will draw conclusions by comparing the control group with the experimental group.

Timeline

Start

2023-05-20

Primary completion

2026-10-31

Completion

2027-03-31

Publications

• Results Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
• Results Wiese L, Hempel C, Penkowa M, Kirkby N, Kurtzhals JA. Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria. Malar J. 2008 Jan 7;7:3. doi: 10.1186/1475-2875-7-3.
• Results Gantner DC, Bailey M, Presneill J, French CJ, Nichol A, Little L, Bellomo R; EPO-TBI Investigators; the ANZICS Clinical Trials Group. Erythropoietin to Reduce Mortality in Traumatic Brain Injury: A Post-hoc Dose-effect Analysis. Ann Surg. 2018 Mar;267(3):585-589. doi: 10.1097/SLA.0000000000002142.
• Results Tsai TH, Lu CH, Wallace CG, Chang WN, Chen SF, Huang CR, Tsai NW, Lan MY, Sung PH, Liu CF, Yip HK. Erythropoietin improves long-term neurological outcome in acute ischemic stroke patients: a randomized, prospective, placebo-controlled clinical trial. Crit Care. 2015 Feb 25;19(1):49. doi: 10.1186/s13054-015-0761-8.
• Results Yip HK, Tsai TH, Lin HS, Chen SF, Sun CK, Leu S, Yuen CM, Tan TY, Lan MY, Liou CW, Lu CH, Chang WN. Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke. Crit Care. 2011;15(1):R40. doi: 10.1186/cc10002. Epub 2011 Jan 26.
• Results Ozawa T, Toba K, Suzuki H, Kato K, Iso Y, Akutsu Y, Kobayashi Y, Takeyama Y, Kobayashi N, Yoshimura N, Akazawa K, Aizawa Y; EPO/AMI-I Pilot Study Researchers. Single-dose intravenous administration of recombinant human erythropoietin is a promising treatment for patients with acute myocardial infarction - randomized controlled pilot trial of EPO/AMI-1 study -. Circ J. 2010 Jul;74(7):1415-23. doi: 10.1253/circj.cj-10-0109. Epub 2010 May 22.
• Results Voors AA, Belonje AM, Zijlstra F, Hillege HL, Anker SD, Slart RH, Tio RA, van 't Hof A, Jukema JW, Peels HO, Henriques JP, Ten Berg JM, Vos J, van Gilst WH, van Veldhuisen DJ; HEBE III Investigators. A single dose of erythropoietin in ST-elevation myocardial infarction. Eur Heart J. 2010 Nov;31(21):2593-600. doi: 10.1093/eurheartj/ehq304. Epub 2010 Aug 29.
• Results Tsai TH, Lu CH, Wallace CG, Chang WN, Chen SF, Huang CR, Tsai NW, Lan MY, Sung PH, Liu CF, Yip HK. Erratum to: Erythropoietin improves long-term neurological outcome in acute ischemic stroke patients: a randomized, prospective, placebo-controlled clinical trial. Crit Care. 2016 Mar 31;20:78. doi: 10.1186/s13054-016-1256-y. No abstract available.
• Results Suhs KW, Hein K, Sattler MB, Gorlitz A, Ciupka C, Scholz K, Kasmann-Kellner B, Papanagiotou P, Schaffler N, Restemeyer C, Bittersohl D, Hassenstein A, Seitz B, Reith W, Fassbender K, Hilgers R, Heesen C, Bahr M, Diem R. A randomized, double-blind, phase 2 study of erythropoietin in optic neuritis. Ann Neurol. 2012 Aug;72(2):199-210. doi: 10.1002/ana.23573.
• Results Corwin HL, Gettinger A, Fabian TC, May A, Pearl RG, Heard S, An R, Bowers PJ, Burton P, Klausner MA, Corwin MJ; EPO Critical Care Trials Group. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med. 2007 Sep 6;357(10):965-76. doi: 10.1056/NEJMoa071533.
• Results Kakavas S, Demestiha T, Vasileiou P, Xanthos T. Erythropoetin as a novel agent with pleiotropic effects against acute lung injury. Eur J Clin Pharmacol. 2011 Jan;67(1):1-9. doi: 10.1007/s00228-010-0938-7. Epub 2010 Nov 11.
• Results Rocha J, Eduardo-Figueira M, Barateiro A, Fernandes A, Brites D, Pinto R, Freitas M, Fernandes E, Mota-Filipe H, Sepodes B. Erythropoietin reduces acute lung injury and multiple organ failure/dysfunction associated to a scald-burn inflammatory injury in the rat. Inflammation. 2015 Feb;38(1):312-26. doi: 10.1007/s10753-014-0035-7.
• Results Tascilar O, Cakmak GK, Tekin IO, Emre AU, Ucan BH, Bahadir B, Acikgoz S, Irkorucu O, Karakaya K, Balbaloglu H, Kertis G, Ankarali H, Comert M. Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis. World J Gastroenterol. 2007 Dec 14;13(46):6172-82. doi: 10.3748/wjg.v13.i46.6172.
• Results MacRedmond R, Singhera GK, Dorscheid DR. Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injury. Eur Respir J. 2009 Jun;33(6):1403-14. doi: 10.1183/09031936.00084608. Epub 2009 Jan 22.
• Results Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003 Aug 15;102(4):1340-6. doi: 10.1182/blood-2003-01-0223. Epub 2003 Apr 17.
• Results Shang Y, Li X, Prasad PV, Xu S, Yao S, Liu D, Yuan S, Feng D. Erythropoietin attenuates lung injury in lipopolysaccharide treated rats. J Surg Res. 2009 Jul;155(1):104-10. doi: 10.1016/j.jss.2008.10.003. Epub 2008 Nov 8.
• Results Ware LB, Matthay MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001 May;163(6):1376-83. doi: 10.1164/ajrccm.163.6.2004035.
• Results Phillips CR, Chesnutt MS, Smith SM. Extravascular lung water in sepsis-associated acute respiratory distress syndrome: indexing with predicted body weight improves correlation with severity of illness and survival. Crit Care Med. 2008 Jan;36(1):69-73. doi: 10.1097/01.CCM.0000295314.01232.BE.

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