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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00221013




Registration number
NCT00221013
Ethics application status
Date submitted
14/09/2005
Date registered
22/09/2005
Date last updated
27/02/2009

Titles & IDs
Public title
Augmented Vs. Normal Renal Replacement Therapy in Severe Acute Renal Failure (ARF).
Scientific title
Multicentre, Unblinded, Open Label, Randomised, Controlled Trial to Assess the Effect of Augmented Vs. Normal Continuous Renal Replacement Therapy (CRRT) on 90-Day All-Cause Mortality of Intensive Care Unit Patients With Severe Acute Renal Failure (ARF).
Secondary ID [1] 0 0
352550
Secondary ID [2] 0 0
GI-RE-ARF001-40-R
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Renal Failure 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - "augmented" CRRT regimen

Experimental: Higher intensity CRRT regimen -

Active comparator: Lower intensity CRRT regimen -


Treatment: Surgery: "augmented" CRRT regimen
We randomly assigned critically ill patients with acute kidney injury to receive CRRT in the form of post-dilution continuous veno-venous hemodiafiltration (CVVHDF) at 25 ml/kg/hr (lower intensity) or 40 ml/kg/hr (higher intensity) of effluent flow.
Intervention code [1] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Death from all causes at 90 days after randomisation.
Timepoint [1] 0 0
Within 90 days after randomisation
Secondary outcome [1] 0 0
Death within the in the intensive care unit.
Timepoint [1] 0 0
0 to 90 days
Secondary outcome [2] 0 0
Death within 28 days of randomisation.
Timepoint [2] 0 0
Within 28 days of randomisation.
Secondary outcome [3] 0 0
Death prior to hospital discharge.
Timepoint [3] 0 0
0 to 90 days
Secondary outcome [4] 0 0
Length of ICU stay.
Timepoint [4] 0 0
0 to 90 days
Secondary outcome [5] 0 0
Length of hospital stay.
Timepoint [5] 0 0
0 to 90 days
Secondary outcome [6] 0 0
The need for and duration of other organ support (inotropic/vasopressor support and positive pressure ventilation).
Timepoint [6] 0 0
0 to 90 days
Secondary outcome [7] 0 0
CRRT-free days.
Timepoint [7] 0 0
0 to 90 days
Secondary outcome [8] 0 0
Dialysis-independent survival.
Timepoint [8] 0 0
0 to 90 days

Eligibility
Key inclusion criteria
1. The treating clinician believes that the patient requires CRRT for acute renal failure.
2. The clinician is uncertain about the balance of benefits and risks likely to be conferred by treatment with higher intensity or lower intensity CRRT.
3. The treating clinicians anticipate treating the patient with CRRT for at least 72 hours.
4. Informed consent has been obtained
5. The patient fulfils ONE of the following clinical criteria for initiating CRRT:

* Oliguria (urine output < 100ml/6hr) that has been unresponsive to fluid resuscitation measures.
* Hyperkalemia ([K+] > 6.5 mmol/L).
* Severe acidemia (pH < 7.2).
* Urea > 25 mmol/liter.
* Creatinine >300 micromol/L in the setting of ARF.
* Clinically significant organ oedema in the setting of ARF (eg: lung).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient age is <18 years.
2. Death is imminent (<24 hours).
3. There is a strong likelihood that the study treatment would not be continued in accordance with the study protocol.
4. The patient has been treated with CRRT or other dialysis previously during the same hospital admission.
5. The patient was on maintenance dialysis prior to the current hospitalisation.
6. The patient's body weight is <60 kg or >100kg.
7. Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study.

Study design
Purpose of the study
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2009
Sample size
Target
Accrual to date
Final
1508
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Austin Hopsital - Heidelberg
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg

Funding & Sponsors
Primary sponsor type
Other
Name
The George Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
ANZICS Clinical Trials Group
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study seeks to determine if increasing the dose of continuous renal replacement therapy (CRRT) reduces 90-day all cause mortality in Intensive Care Unit (ICU) patients with severe acute renal failure (ARF).
Trial website
https://clinicaltrials.gov/study/NCT00221013
Trial related presentations / publications
RENAL Study Investigators. Renal replacement therapy for acute kidney injury in Australian and New Zealand intensive care units: a practice survey. Crit Care Resusc. 2008 Sep;10(3):225-30.
RENAL Study Investigators; Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Goldsmith D, Myburgh J, Norton R, Scheinkestel C. Design and challenges of the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) Trial: high-dose versus standard-dose hemofiltration in acute renal failure. Blood Purif. 2008;26(5):407-16. doi: 10.1159/000148400.
Naorungroj T, Neto AS, Wang A, Gallagher M, Bellomo R. Renal outcomes according to renal replacement therapy modality and treatment protocol in the ATN and RENAL trials. Crit Care. 2022 Sep 6;26(1):269. doi: 10.1186/s13054-022-04151-5.
Tsujimoto Y, Miki S, Shimada H, Tsujimoto H, Yasuda H, Kataoka Y, Fujii T. Non-pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2021 Sep 14;9(9):CD013330. doi: 10.1002/14651858.CD013330.pub2.
Serpa Neto A, Naorungroj T, Murugan R, Kellum JA, Gallagher M, Bellomo R. Heterogeneity of Effect of Net Ultrafiltration Rate among Critically Ill Adults Receiving Continuous Renal Replacement Therapy. Blood Purif. 2021;50(3):336-346. doi: 10.1159/000510556. Epub 2020 Oct 7.
Murugan R, Kerti SJ, Chang CH, Gallagher M, Clermont G, Palevsky PM, Kellum JA, Bellomo R. Association of Net Ultrafiltration Rate With Mortality Among Critically Ill Adults With Acute Kidney Injury Receiving Continuous Venovenous Hemodiafiltration: A Secondary Analysis of the Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy Trial. JAMA Netw Open. 2019 Jun 5;2(6):e195418. doi: 10.1001/jamanetworkopen.2019.5418.
Wang AY, Trongtrakul K, Bellomo R, Li Q, Cass A, Gallagher M; RENAL Study Investigators and the ANZICS Clinical Trials Group. HMG-CoA reductase inhibitors (statins) and acute kidney injury: A secondary analysis of renal study outcomes. Nephrology (Carlton). 2019 Sep;24(9):912-918. doi: 10.1111/nep.13597. Epub 2019 May 27.
Roberts DM, Liu X, Roberts JA, Nair P, Cole L, Roberts MS, Lipman J, Bellomo R; RENAL Replacement Therapy Study Investigators. A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics. Crit Care. 2015 Mar 13;19(1):84. doi: 10.1186/s13054-015-0818-8.
Wang AY, Bellomo R, Ninomiya T, Lo S, Cass A, Jardine M, Gallagher M; RENAL Study Investigators; ANZICS Clinical Trials Group. Angiotensin-converting enzyme inhibitor usage and acute kidney injury: a secondary analysis of RENAL study outcomes. Nephrology (Carlton). 2014 Oct;19(10):617-22. doi: 10.1111/nep.12284.
Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lee J, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C; RENAL Study Investigators; Su S. Calorie intake and patient outcomes in severe acute kidney injury: findings from The Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study trial. Crit Care. 2014 Mar 14;18(2):R45. doi: 10.1186/cc13767.
Gallagher M, Cass A, Bellomo R, Finfer S, Gattas D, Lee J, Lo S, McGuinness S, Myburgh J, Parke R, Rajbhandari D; POST-RENAL Study Investigators and the ANZICS Clinical Trials Group. Long-term survival and dialysis dependency following acute kidney injury in intensive care: extended follow-up of a randomized controlled trial. PLoS Med. 2014 Feb 11;11(2):e1001601. doi: 10.1371/journal.pmed.1001601. eCollection 2014 Feb.
Bellomo R, Lipcsey M, Calzavacca P, Haase M, Haase-Fielitz A, Licari E, Tee A, Cole L, Cass A, Finfer S, Gallagher M, Lee J, Lo S, McArthur C, McGuinness S, Myburgh J, Scheinkestel C; RENAL Study Investigators and ANZICS Clinical Trials Group. Early acid-base and blood pressure effects of continuous renal replacement therapy intensity in patients with metabolic acidosis. Intensive Care Med. 2013 Mar;39(3):429-36. doi: 10.1007/s00134-012-2800-0. Epub 2013 Jan 11.
RENAL Replacement Therapy Study Investigators; Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009 Oct 22;361(17):1627-38. doi: 10.1056/NEJMoa0902413.
Public notes

Contacts
Principal investigator
Name 0 0
Prof Rinaldo Bellomo, MD
Address 0 0
Austin Hospital, Melbourne Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00221013