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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.
This study was designed as a double-blind, randomized controlled trial. Neither the subject nor the investigator knew the allocation of treatment drugs. Subjects signed the informed consent form, completed all screening assessments, and were randomized in the order of screening eligibility after screening eligibility. The investigator or designee generated the corresponding case number and drug number using a simple randomization method. Information about the subject's trial product allocation was placed in an emergency envelope and retained by the investigator for use in an emergency. Randomised subjects who withdraw from the clinical trial for any reason, regardless of whether they have taken the trial medication, will retain their case number and medication number and will not be allowed to re-enter the trial.
The investigator participating in this trial is a clinician with appropriate experience, who can make treatment decision based on the clinical response and laboratory test results of the subject. The specific process of the study is as follows:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Erythropoietin group | Experimental | intravenous injection of 40000iu of rhEPO |
|
| 0.9%NS | Placebo Comparator | intravenous injection of the same volume of 0.9%NS as the test group |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Human erythropoietin injection | Drug | Each subject in the test group received 40000iu of human erythropoietin intravenously |
|
| Measure | Description | Time Frame |
|---|---|---|
| EVLWI | extravascular lung water index | Changes of EVLWI at 0,6,12,24 ,48 and 72 hours after intervention |
| PVPI | pulmonary vascular permeability index | Changes of PVPI at 0,6,12,24 ,48 and 72 hours after intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Survival rate | 28-day survival rate | 28-day hospital survival |
| Oxygenation index | PaO2/FiO2 | Changes of oxygenation index at 0, 1, 2 and 3 days after intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Shengwei Jin, Professor | Contact | 13616663961 | jinshengwei69@163.com | |
| Yuqiang Gong, Professor | Contact | 13858785608 | gyq12120@163.com@163 |
| Name | Affiliation | Role |
|---|---|---|
| Ye Gao, PhD | Second Affiliated Hospital of Wenzhou Medical University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| SAHWenzhouMU | Recruiting | Wenzhou | Zhejiang | 325000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26903337 | Result | 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. | |
| 18179698 |
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| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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| 0.9%NaCl | Drug | Each subject in the control group was injected with an equal volume of 0.9%NaCl |
|
|
| Result |
| 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. |
| 28151802 | Result | 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. |
| 25888250 | Result | 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. |
| 21269484 | Result | 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. |
| 20501957 | Result | 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. |
| 20802250 | Result | 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. |
| 27037155 | Result | 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. |
| 22926853 | Result | 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. |
| 17804841 | Result | 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. |
| 21069520 | Result | 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. |
| 25270658 | Result | 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. |
| 18069756 | Result | 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. |
| 19164355 | Result | 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. |
| 12702503 | Result | 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. |
| 19285686 | Result | 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. |
| 11371404 | Result | 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. |
| 18090369 | Result | 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. |
| D017670 |
| Sodium Compounds |