Clinical trial NCT01961999: Early Versus Late Renal Replacement Therapy After Cardiac Surgery
Official title: "Early" and "Late" Timing Indication for Starting Renal Replacement Therapy in Acute Renal Failure After Cardiac Surgery: a Prospective, Controlled, Interventional, Single-center Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Kidney Injury
Keywords: Acute kidney injury
Cardiac surgery
Renal replacement therapy
Lead sponsor: Ospedali Riuniti Ancona
Sponsor class: OTHER
First posted: 2013-10-14
Enrollment: 1800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The question of timing of initiation of renal replacement therapy (RRT), "early" versus "late", has seldom been the focus of high-quality or rigorous evaluation. As a consequence, initiatives aimed at identifying the "optimal timing of initiation of RRT" in acute kidney injury (AKI) have been given the highest priority for investigation by the Acute Kidney Injury Network (AKIN). Accordingly, the investigators conducted a prospective, controlled, interventional trial, comparing two treatment groups in which the only variable was the RRT initiation strategy, to determine whether "early" versus "late" initiation in patients with AKI after cardiac surgery is associated with a survival benefit or more favorable outcomes.

Detailed description: Acute kidney injury after cardiac surgery is strongly associated with in-hospital mortality and morbidity. This is an area where effective treatments are lacking and trial are difficult to perform. To date no randomized controlled trial (RCT) has sufficiently estimated the impact of RRT timing of initiation on patient outcome, and the present prospective, controlled, interventional, single-center trial attempts to compare patient outcome with "early" versus "late" initiation of RRT. Previous studies in cardiac surgery setting have been retrospective ones and have been hampered by lead-time bias, and drop out patients. To overcome these biases all patients who underwent cardiac surgery were prospectively enrolled in the trial and were divided in two treatment groups: the "early" approach was used during the first 10-months, and the "late" approach during the next 10-months. To improve the information gained from this non-classical randomized study and to minimize bias, the investigators enrolled almost all patients with few exclusion criteria during two following short periods, used intention-to-treat analysis and treated all patients according to local protocols and international guidelines, except for RRT initiation strategy.

Outcome parameters were hospital mortality, and ICU and hospital length of stay.

"Early" therapy was started after 6 hours of urine output of less than\<0,5ml/Kg/h, whereas in the "late" group RRT therapy was started on the basis of persistent (lasting more than 12 hours) oliguria.

Data obtained from the database were analyzed using "Statistical Package for Social Science" (SPSS Inc, Chicago, IL). Continuous variables are presented as mean±SD, categorical variables were summarized as frequencies and percentages. The Student t test or Pearson X square test were performed to evaluate differences between groups and to analyze subgroups. For statistics, a p\<0.05 was considered significant.

Power calculation was based on previous reports13 on cumulative mortality following cardiac surgery. 50% reduction of mortality was hypothesized when the more conservative approach to cardiac surgery-AKI was applied. The suggested number of patients was about 900 patients per group.

The main limitation of the present study include the non-classical randomization, nevertheless we conducted an interventional trial comparing two treatment strategies in two different groups of patients, prospectively followed and suitable for both treatments.

Eligibility criteria: Inclusion criteria:

* Patients submitted to cardiac surgery at "Ospedali Riuniti" of Ancona during the study period
* Planned use of extracorporeal circulation

Exclusion criteria:

* Preoperative dialysis
* Planned off-pump cardiac surgery
* Pts (or proxy) did not sign informed consent

Primary outcomes:
measure: operative mortality
timeFrame: death during the same hospitalization as surgery, or after discharge, but within 30 days of surgery
Secondary outcomes:
measure: Hospital length of stay
timeFrame: during the same hospitalization for surgery, but within 30 days from surgery
measure: ICU length of stay
timeFrame: during the same hospitalization for surgery, but within 30 days from surgery
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Cardiac Surgery department of Ospedali Riuniti
state: AN
Study officials:
affiliation: Ospedali Riuniti di Ancona
name: Giuseppe Crescenzi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Karkouti K, Wijeysundera DN, Yau TM, Callum JL, Cheng DC, Crowther M, Dupuis JY, Fremes SE, Kent B, Laflamme C, Lamy A, Legare JF, Mazer CD, McCluskey SA, Rubens FD, Sawchuk C, Beattie WS. Acute kidney injury after cardiac surgery: focus on modifiable risk factors. Circulation. 2009 Feb 3;119(4):495-502. doi: 10.1161/CIRCULATIONAHA.108.786913. Epub 2009 Jan 19.
citation: Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative workgroup. 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 Aug;8(4):R204-12. doi: 10.1186/cc2872. Epub 2004 May 24.
citation: Gibney N, Hoste E, Burdmann EA, Bunchman T, Kher V, Viswanathan R, Mehta RL, Ronco C. Timing of initiation and discontinuation of renal replacement therapy in AKI: unanswered key questions. Clin J Am Soc Nephrol. 2008 May;3(3):876-80. doi: 10.2215/CJN.04871107. Epub 2008 Mar 5.
citation: Chertow GM, Lazarus JM, Christiansen CL, Cook EF, Hammermeister KE, Grover F, Daley J. Preoperative renal risk stratification. Circulation. 1997 Feb 18;95(4):878-84. doi: 10.1161/01.cir.95.4.878.
citation: 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 Oct;30(10):2205-11. doi: 10.1097/00003246-200210000-00005.
citation: Korevaar JC, Jansen MA, Dekker FW, Jager KJ, Boeschoten EW, Krediet RT, Bossuyt PM; Netherlands Cooperative Study on the Adequacy of Dialysis Study Group. When to initiate dialysis: effect of proposed US guidelines on survival. Lancet. 2001 Sep 29;358(9287):1046-50. doi: 10.1016/S0140-6736(01)06180-3.
citation: Prowle JR, Bellomo R. Continuous renal replacement therapy: recent advances and future research. Nat Rev Nephrol. 2010 Sep;6(9):521-9. doi: 10.1038/nrneph.2010.100. Epub 2010 Jul 20.
citation: Bagshaw SM, Gibney RT, McAlister FA, Bellomo R. The SPARK Study: a phase II randomized blinded controlled trial of the effect of furosemide in critically ill patients with early acute kidney injury. Trials. 2010 May 11;11:50. doi: 10.1186/1745-6215-11-50.
citation: Akins CW, Miller DC, Turina MI, Kouchoukos NT, Blackstone EH, Grunkemeier GL, Takkenberg JJ, David TE, Butchart EG, Adams DH, Shahian DM, Hagl S, Mayer JE, Lytle BW; Councils of the American Association for Thoracic Surgery; Society of Thoracic Surgeons; European Assoication for Cardio-Thoracic Surgery; Ad Hoc Liaison Committee for Standardizing Definitions of Prosthetic Heart Valve Morbidity. Guidelines for reporting mortality and morbidity after cardiac valve interventions. J Thorac Cardiovasc Surg. 2008 Apr;135(4):732-8. doi: 10.1016/j.jtcvs.2007.12.002. No abstract available.
citation: Kuitunen A, Vento A, Suojaranta-Ylinen R, Pettila V. Acute renal failure after cardiac surgery: evaluation of the RIFLE classification. Ann Thorac Surg. 2006 Feb;81(2):542-6. doi: 10.1016/j.athoracsur.2005.07.047.
citation: Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med. 2006 Jul;34(7):1913-7. doi: 10.1097/01.CCM.0000224227.70642.4F.
citation: Cooper WA, O'Brien SM, Thourani VH, Guyton RA, Bridges CR, Szczech LA, Petersen R, Peterson ED. Impact of renal dysfunction on outcomes of coronary artery bypass surgery: results from the Society of Thoracic Surgeons National Adult Cardiac Database. Circulation. 2006 Feb 28;113(8):1063-70. doi: 10.1161/CIRCULATIONAHA.105.580084. Epub 2006 Feb 20.
citation: Pierri MD, Capestro F, Zingaro C, Torracca L. The changing face of cardiac surgery patients: an insight into a Mediterranean region. Eur J Cardiothorac Surg. 2010 Oct;38(4):407-13. doi: 10.1016/j.ejcts.2010.02.040.
citation: Bove T, Calabro MG, Landoni G, Aletti G, Marino G, Crescenzi G, Rosica C, Zangrillo A. The incidence and risk of acute renal failure after cardiac surgery. J Cardiothorac Vasc Anesth. 2004 Aug;18(4):442-5. doi: 10.1053/j.jvca.2004.05.021.
citation: Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med. 1998 Apr;104(4):343-8. doi: 10.1016/s0002-9343(98)00058-8.
citation: 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 Mar;24(1):129-40. doi: 10.1016/j.jcrc.2007.12.017. Epub 2008 Apr 18.
citation: Pannu N, Klarenbach S, Wiebe N, Manns B, Tonelli M; Alberta Kidney Disease Network. Renal replacement therapy in patients with acute renal failure: a systematic review. JAMA. 2008 Feb 20;299(7):793-805. doi: 10.1001/jama.299.7.793.
citation: 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 Soc Nephrol. 2006 Sep;1(5):915-9. doi: 10.2215/CJN.01430406. Epub 2006 Jul 6.
citation: Metnitz PG, Krenn CG, Steltzer H, Lang T, Ploder J, Lenz K, Le Gall JR, Druml W. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med. 2002 Sep;30(9):2051-8. doi: 10.1097/00003246-200209000-00016.
citation: Ympa YP, Sakr Y, Reinhart K, Vincent JL. Has mortality from acute renal failure decreased? A systematic review of the literature. Am J Med. 2005 Aug;118(8):827-32. doi: 10.1016/j.amjmed.2005.01.069.
citation: Kellum JA. Acute kidney injury. Crit Care Med. 2008 Apr;36(4 Suppl):S141-5. doi: 10.1097/CCM.0b013e318168c4a4.
citation: Crescenzi G, Torracca L, Pierri MD, Rosica C, Munch C, Capestro F. 'Early' and 'late' timing for renal replacement therapy in acute kidney injury after cardiac surgery: a prospective, interventional, controlled, single-centre trial. Interact Cardiovasc Thorac Surg. 2015 May;20(5):616-21. doi: 10.1093/icvts/ivv025. Epub 2015 Feb 18.