title: The SPARK Study: a phase II randomized blinded controlled trial of the effect of furosemide in critically ill patients with early acute kidney injury.
abstract: BACKGROUND
  Furosemide is commonly prescribed in critically ill patients with acute kidney injury (AKI). Existing data from observational studies and small clinical trials have significant limitations and have reported conflicting findings. There remains controversy on whether furosemide can impact clinical outcomes in critically ill patients with AKI; however, a survey of intensivists and nephrologists showed equipoise for high-quality evidence on this important issue.
  
  
  METHODS
  This protocol summarizes the rationale and design of a phase II randomized, blinded, placebo-controlled trial of a low-dose continuous infusion of furosemide, titrated to the physiology parameter of urine output, in critically ill patients with early AKI. Two hundred sixteen adult critically ill patients with early evidence of AKI, defined by the RIFLE criteria, will be enrolled. Included patients will also have fulfilled >or=2 criteria of the systemic inflammatory response syndrome and achieved immediate goals of acute resuscitation. The primary outcome is progression in severity of kidney injury. Secondary outcomes include: safety, fluid balance, electrolyte balance, the need for renal replacement therapy, duration of AKI, rate of renal recovery, mortality and changes in novel serum and urine biomarkers of AKI. The primary analysis will be intention-to-treat. Planned recruitment will be complete by June 2011 and results available by December 2011.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier NCT00978354.
authors.affiliation: Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta,12 Walter C, Mackenzie Centre, 8440-112 Street, Edmonton, Alberta, Canada. bagshaw@ualberta.ca
authors.forename: Sean M
authors.initials: SM
authors.lastname: Bagshaw
authors.forename: R T Noel
authors.initials: RT
authors.lastname: Gibney
authors.forename: Finlay A
authors.initials: FA
authors.lastname: McAlister
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D000208:Acute Disease; D000328:Adult; D000416:Alberta; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016638:Critical Illness; D018450:Disease Progression; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D012107:Research Design; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004232:Diuretics; D005665:Furosemide
references.citation: JAMA. 2002 Nov 27;288(20):2547-53
references.pmid: 12444861
references.citation: Crit Care Med. 2004 Aug;32(8):1794-5
references.pmid: 15286565
references.citation: Blood Purif. 1997;15(4-6):319-22
references.pmid: 9435960
references.citation: Kidney Int Suppl. 1998 May;66:S16-24
references.pmid: 9580541
references.citation: Nephron. 1976;17(1):51-8
references.pmid: 778649
references.citation: Contrib Nephrol. 2007;156:236-49
references.pmid: 17464133
references.citation: Am J Physiol. 1978 Aug;235(2):F131-6
references.pmid: 686175
references.citation: N Engl J Med. 1973 Apr 5;288(14):695-9
references.pmid: 4631743
references.citation: Ann Thorac Surg. 2000 Feb;69(2):501-6
references.pmid: 10735688
references.citation: JAMA. 2005 Aug 17;294(7):813-8
references.pmid: 16106006
references.citation: Surg Forum. 1976;27(62):27-9
references.pmid: 1019883
references.citation: Nephrol Dial Transplant. 1997 Dec;12(12):2592-6
references.pmid: 9430857
references.citation: J Am Soc Nephrol. 2006 Apr;17(4):1135-42
references.pmid: 16495381
references.citation: JAMA. 2002 Nov 27;288(20):2599-601
references.pmid: 12444868
references.citation: Curr Opin Crit Care. 2005 Dec;11(6):537-41
references.pmid: 16292056
references.citation: JAMA. 2009 Sep 16;302(11):1179-85
references.pmid: 19755696
references.citation: Crit Care. 2005;9(6):R700-9
references.pmid: 16280066
references.citation: Intensive Care Med. 2000 Dec;26(12):1824-31
references.pmid: 11271091
references.citation: Ren Fail. 2006;28(1):25-35
references.pmid: 16526316
references.citation: Am J Kidney Dis. 2004 Sep;44(3):402-9
references.pmid: 15332212
references.citation: Surgery. 1977 Sep;82(3):341-20
references.pmid: 888101
references.citation: BMJ. 2006 Aug 26;333(7565):420
references.pmid: 16861256
references.citation: J Am Soc Nephrol. 2007 Apr;18(4):1292-8
references.pmid: 17314324
references.citation: Nephron. 1992;62(4):413-5
references.pmid: 1300436
references.citation: Clin J Am Soc Nephrol. 2007 May;2(3):431-9
references.pmid: 17699448
references.citation: Best Pract Res Clin Anaesthesiol. 2004 Mar;18(1):75-89
references.pmid: 14760875
references.citation: Postgrad Med J. 1971 Apr;47:Suppl:13-7
references.pmid: 5579763
references.citation: J Indian Med Assoc. 1975 Jan 16;64(2):47-8
references.pmid: 1133468
references.citation: Br Med J. 1974 May 4;2(5913):278-9
references.pmid: 4827098
references.citation: Crit Care. 2008;12(3):R74
references.pmid: 18533029
references.citation: Chest. 1992 Jun;101(6):1644-55
references.pmid: 1303622
references.citation: Crit Care Med. 2003 Feb;31(2):449-55
references.pmid: 12576950
references.citation: Crit Care. 2006;10(3):R73
references.pmid: 16696865
references.citation: Crit Care. 2007;11(3):R68
references.pmid: 17588270
references.citation: Crit Care Resusc. 2007 Mar;9(1):60-8
references.pmid: 17352669
references.citation: Ren Fail. 2005;27(4):385-92
references.pmid: 16060124
references.citation: Ren Fail. 2007;29(4):399-407
references.pmid: 17497460
references.citation: Crit Care. 2004 Aug;8(4):R204-12
references.pmid: 15312219
references.citation: Ann Intern Med. 1997 Aug 1;127(3):195-202
references.pmid: 9245224
references.citation: Br Med J. 1973 Nov 24;4(5890):449-50
references.pmid: 4758446
references.citation: Br Med J. 1973 Dec 29;4(5895):784
references.pmid: 4758583
references.citation: Nephron Clin Pract. 2007;107(2):c70-6
references.pmid: 17890871
references.citation: Kidney Int. 2009 Aug;76(4):422-7
references.pmid: 19436332
references.citation: Crit Care Med. 2004 Aug;32(8):1669-77
references.pmid: 15286542
references.citation: Crit Care Med. 2002 Sep;30(9):2051-8
references.pmid: 12352040
references.citation: Kidney Int. 1980 Apr;17(4):455-64
references.pmid: 7392420