Early Versus Late Renal Replacement Therapy After Cardiac Surgery

NCT ID: NCT01961999

Last Updated: 2013-10-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

1800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-31

Study Completion Date

2013-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Kidney Injury

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Acute kidney injury Cardiac surgery Renal replacement therapy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Early RRT

In the "early" arm renal replacement therapy was started on the basis of refractory oliguria: urine output \<0,5ml/Kg/h for \> 6 hours

Group Type ACTIVE_COMPARATOR

Early RRT

Intervention Type PROCEDURE

In the "early" arm renal replacement therapy was started on the basis of refractory oliguria: urine output \<0,5ml/Kg/h for \> 6 hours

Late RRT

In the "late" arm at least one the following criteria must be fulfilled prior to initiation of renal replacement therapy:

* persistent and refractory oliguria (\<0,5 ml/Kg/h \>12h), despite therapy
* refractory extravascular fluid overload
* azotemia \> 40mmol/L or 240 mg/dL
* metabolic acidosis (pH\<7,2)
* hyperkaliemia (k+\>6 mmol/L)

Group Type ACTIVE_COMPARATOR

Late RRT

Intervention Type PROCEDURE

In the "late" arm at least one the following criteria must be fulfilled prior to initiation of renal replacement therapy:

persistent and refractory oliguria (\<0,5ml/Kg/h \>12h), despite therapy refractory extravascular fluid overload azotemia \>40mmol/L or 240mg/dL metabolic acidosis (pH\<7,2) hyperkaliemia (k+\>6mmol/L)

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Early RRT

In the "early" arm renal replacement therapy was started on the basis of refractory oliguria: urine output \<0,5ml/Kg/h for \> 6 hours

Intervention Type PROCEDURE

Late RRT

In the "late" arm at least one the following criteria must be fulfilled prior to initiation of renal replacement therapy:

persistent and refractory oliguria (\<0,5ml/Kg/h \>12h), despite therapy refractory extravascular fluid overload azotemia \>40mmol/L or 240mg/dL metabolic acidosis (pH\<7,2) hyperkaliemia (k+\>6mmol/L)

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Ospedali Riuniti Ancona

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Giuseppe Crescenzi M.D.

Medical Doctor Cardiac Surgery intensive care Unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Giuseppe Crescenzi, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedali Riuniti di Ancona

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Cardiac Surgery department of Ospedali Riuniti

Ancona, AN, Italy

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Italy

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 19153273 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15312219 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18322044 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9054745 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12394945 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11589934 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20644583 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20459801 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18374749 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16427848 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16715038 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16490821 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20399675 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15365924 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9576407 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19272549 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18285591 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17699307 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12352040 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16084171 (View on PubMed)

Kellum JA. Acute kidney injury. Crit Care Med. 2008 Apr;36(4 Suppl):S141-5. doi: 10.1097/CCM.0b013e318168c4a4.

Reference Type BACKGROUND
PMID: 18382185 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25694207 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ANCCH01

Identifier Type: -

Identifier Source: org_study_id