Impact on mortality of the timing of renal replacement therapy in patients with severe acute kidney injury in septic shock: the IDEAL-ICU study (initiation of dialysis early versus delayed in the intensive care unit): study protocol for a randomized controlled trial

Saber Davide Barbar, Christine Binquet, Mehran Monchi, Rémi Bruyère, Jean-Pierre Quenot, Saber Davide Barbar, Christine Binquet, Mehran Monchi, Rémi Bruyère, Jean-Pierre Quenot

Abstract

Background: One of the most dreaded complications of septic shock is acute kidney injury. It occurs in around 50% of patients, with a mortality rate of about 60% at 3 months. There is no consensus on the optimal time to initiate renal replacement therapy. Retrospective and observational studies suggest that early implementation of renal replacement therapy could improve the prognosis for these patients.

Methods/design: This protocol summarizes the rationale and design of a randomized, controlled, multicenter trial investigating the effect of early versus delayed renal replacement therapy in patients with severe acute kidney injury in early septic shock. In total, 864 critically ill adults with septic shock and evidence of acute kidney injury, defined as the failure stage of the RIFLE classification, will be enrolled. The primary outcome is mortality at 90 days. Secondary outcomes include safety, number of days free of mechanical ventilation, number of days free of renal replacement therapy, intensive care length of stay, in-hospital length of stay, quality of life as evaluated by the EQ-5D and renal replacement therapy dependence at hospital discharge. The primary analysis will be intention to treat. Recruitment started in March 2012 and will be completed by March 2015.

Discussion: This protocol for a randomized controlled study investigating the impact of the timing of renal replacement therapy initiation should provide an answer to a key question for the management of patients with acute kidney injury in the context of septic shock, for whom the mortality rate remains close to 60% despite improved understanding of physiopathology and recent therapeutic advances.

Trial registration: ClinicalTrials.gov identifier NCT01682590, registered on 10 September 2012.

Figures

Figure 1
Figure 1
Flow chart of the study groups. The timing of diagnosis, randomization and initiation of renal replacement therapy in the early and delayed groups, according to the method used to diagnosis acute kidney injury, are shown.

References

    1. Pavon A, Binquet C, Kara F, Martinet O, Ganster F, Navellou JC, Castelain V, Barraud D, Cousson J, Louis G, Perez P, Kuteifan K, Noirot A, Badie J, Mezher C, Lessire H, Quantin C, Abrahamowicz M, Quenot JP. EPIdemiology of Septic Shock (EPISS) Study Group. Profile of the risk of death after septic shock in the present era: an epidemiologic study. Crit Care Med. 2013;41:2600–2609.
    1. Quenot JP, Binquet C, Kara F, Martinet O, Ganster F, Navellou JC, Castelain V, Barraud D, Cousson J, Louis G, Perez P, Kuteifan K, Noirot A, Badie J, Mezher C, Lessire H, Pavon A. The epidemiology of septic shock in French intensive care units: the prospective multicenter cohort EPISS study. Crit Care. 2013;17:R65.
    1. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med. 2004;351:159–169.
    1. Bagshaw SM, George C, Bellomo R. Early acute kidney injury and sepsis: a multicentre evaluation. Crit Care. 2008;12:R47.
    1. Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359:7–20.
    1. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–818.
    1. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten HM, Ronco C, Kellum JA. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol. 2007;2:431–439.
    1. Langenberg C, Wan L, Egi M, May CN, Bellomo R. Renal blood flow and function during recovery from experimental septic acute kidney injury. Intensive Care Med. 2007;33:1614–1618.
    1. Cooper BA, Branley P, Bulfone L, Collins JF, Craig JC, Fraenkel MB, Harris A, Johnson DW, Kesselhut J, Li JJ, Luxton G, Pilmore A, Tiller DJ, Harris DC, Pollock CA. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010;363:609–619.
    1. Clark E, Wald R, Levin A, Bouchard J, Adhikari NK, Hladunewich M, Richardson RM, James MT, Walsh MW, House AA, Moist L, Stollery DE, Burns KE, Friedrich JO, Barton J, Lafrance JP, Pannu N, Bagshaw SM. Canadian Acute Kidney Injury (CANAKI) Investigators. Timing the initiation of renal replacement therapy for acute kidney injury in Canadian intensive care units: a multicentre observational study. Can J Anaesth. 2012;59:861–870.
    1. Thakar CV, Rousseau J, Leonard AC. Timing of dialysis initiation in AKI in ICU: international survey. Crit Care. 2012;16:R237.
    1. Bagshaw SM, Lapinsky S, Dial S, Arabi Y, Dodek P, Wood G, Ellis P, Guzman J, Marshall J, Parrillo JE, Skrobik Y, Kumar A. Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med. 2009;35:871–881.
    1. Teschan PE, Baxter CR, O’Brien TF, Freyhof JN, Hall WH. Prophylactic hemodialysis in the treatment of acute renal failure. Ann Intern Med. 1960;53:992–1016.
    1. Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, Zandstra DF, Kesecioglu J. Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial. Crit Care Med. 2002;30:2205–2211.
    1. Elahi MM, Lim MY, Joseph RN, Dhannapuneni RR, Spyt TJ. Early hemofiltration improves survival in post-cardiotomy patients with acute renal failure. Eur J CardiothoracSurg. 2004;26:1027–1031.
    1. Gettings LG, Reynolds HN, Scalea T. Outcome in post-traumatic acute renal failure when continuous renal replacement therapy is applied early vs. late. Intensive Care Med. 1999;25:805–813.
    1. Liu KD, Himmelfarb J, Paganini E, Ikizler TA, Soroko SH, Mehta RL, Chertow GM. Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am SocNephrol. 2006;1:915–919.
    1. Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL. Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis. Am J Kidney Dis. 2008;52:272–284.
    1. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten HM, Ronco C, Kellum JA. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury. J Crit Care. 2009;24:129–140.
    1. Payen D, Mateo J, Cavaillon JM, Fraisse F, Floriot C, Vicaut E. Impact of continuous venovenous hemofiltration on organ failure during the early phase of severe sepsis: a randomized controlled trial. Crit Care Med. 2009;37:803–810.
    1. Piccinni P, Dan M, Barbacini S, Carraro R, Lieta E, Marafon S, Zamperetti N, Brendolan A, D’Intini V, Tetta C, Bellomo R, Ronco C. Early isovolaemic haemofiltration in oliguric patients with septic shock. Intensive Care Med. 2006;32:80–86.
    1. Shiao CC, Ko WJ, Wu VC, Huang TM, Lai CF, Lin YF, Chao CT, Chu TS, Tsai HB, Wu PC, Young GH, Kao TW, Huang JW, Chen YM, Lin SL, Wu MS, Tsai PR, Wu KD, Wang MJ. National Taiwan University Hospital Study Group on Acute Renal Failure (NSARF) U-curve association between timing of renal replacement therapy initiation and in-hospital mortality in postoperative acute kidney injury. PLoS One. 2012;7:e42952.
    1. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204–R212.
    1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R. Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165–228.
    1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med. 2001;2003(31):1250–1256.
    1. Mehta RL, McDonald B, Gabbai FB, Pahl M, Pascual MT, Farkas A, Kaplan RM. A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Kidney Int. 2001;60:1154–1163.
    1. Vinsonneau C, Camus C, Combes A, de Costa Beauregard MA, Klouche K, Boulain T, Pallot JL, Chiche JD, Taupin P, Landais P, Dhainaut JF. Continuous venovenoushaemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentrerandomised trial. Lancet. 2006;368:379–385.
    1. Brochard L, Abroug F, Brenner M, Broccard AF, Danner RL, Ferrer M, Laghi F, Magder S, Papazian L, Pelosi P, Polderman KH. An official ATS/ERS/ESICM/SCCM/SRLF statement: prevention and management of acute renal failure in the ICU patient: an international consensus conference in intensive care medicine. Am J RespirCrit Care Med. 2010;181:1128–1155.
    1. Disease K. Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int. 2012;2(Suppl):1–138.
    1. Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001;33:337–343.
    1. Abrahamowicz M, MacKenzie TA. Joint estimation of time-dependent and non-linear effects of continuous covariates on survival. Stat Med. 2007;26:392–408.
    1. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer. 1976;34:585–612.
    1. Lopes JA, Fernandes P, Jorge S, Goncalves S, Alvarez A, CostaeSilva Z, Franca C, Prata MM. Acute kidney injury in intensive care unit patients: a comparison between the RIFLE and the acute kidney injury network classifications. Crit Care. 2008;12:R110.
    1. Kellum JA, Levin N, Bouman C, Lameire N. Developing a consensus classification system for acute renal failure. Curr Opin Crit Care. 2002;8:509–514.
    1. Ostermann M, Chang RW. Acute kidney injury in the intensive care unit according to RIFLE. Crit Care Med. 2007;35:1837–1843.
    1. Thakar CV, Christianson A, Freyberg R, Almenoff P, Render ML. Incidence and outcomes of acute kidney injury in intensive care units: a veterans administration study. Crit Care Med. 2009;37:2552–2558.
    1. Bagshaw SM, George C, Dinu I, Bellomo R. A multi-centre evaluation of the RIFLE criteria for early acute kidney injury in critically ill patients. Nephrol Dial Transplant. 2008;23:1203–1210.
    1. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31.
    1. Bagshaw SM, George C, Bellomo R. A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients. Nephrol Dial Transplant. 2008;23:1569–1574.
    1. Joannidis M, Metnitz B, Bauer P, Schusterschitz N, Moreno R, Druml W, Metnitz PG. Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med. 2009;35:1692–1702.

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