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Augmented Vs. Normal Renal Replacement Therapy in Severe Acute Renal Failure (ARF).

This study has been completed.
Sponsor:
Collaborator:
ANZICS Clinical Trials Group
Information provided by:
The George Institute
ClinicalTrials.gov Identifier:
NCT00221013
First received: September 14, 2005
Last updated: February 25, 2009
Last verified: February 2009

September 14, 2005
February 25, 2009
November 2005
October 2008   (final data collection date for primary outcome measure)
Death from all causes at 90 days after randomisation. [ Time Frame: Within 90 days after randomisation ] [ Designated as safety issue: No ]
Death from all causes at 90 days after randomisation.
Complete list of historical versions of study NCT00221013 on ClinicalTrials.gov Archive Site
  • Death within the in the intensive care unit. [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • Death within 28 days of randomisation. [ Time Frame: Within 28 days of randomisation. ] [ Designated as safety issue: No ]
  • Death prior to hospital discharge. [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • Length of ICU stay. [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • Length of hospital stay. [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • The need for and duration of other organ support (inotropic/vasopressor support and positive pressure ventilation). [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • CRRT-free days. [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • Dialysis-independent survival. [ Time Frame: 0 to 90 days ] [ Designated as safety issue: No ]
  • Death within the in the intensive care unit.
  • Death within 28 days of randomisation.
  • Death prior to hospital discharge.
  • Length of ICU stay.
  • Length of hospital stay.
  • The need for and duration of other organ support (inotropic/vasopressor support and positive pressure ventilation).
  • CRRT-free days.
  • Dialysis-independent survival.
Not Provided
Not Provided
 
Augmented Vs. Normal Renal Replacement Therapy in Severe Acute Renal Failure (ARF).
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).

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).

Study Title - Multicentre, Unblinded, 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).

Clinical Phase - IV

Study Rationale - This study will provide high quality evidence from a mulit-center randomised controlled trial about the comparative effects of different targets for CRRT dose in patients with ARF treated in the Australasian intensive care setting. This evidence will have direct relevance to decisions about the care of critically ill patients admitted to intensive care units in Australia and New Zealand. If this study confirms the treatment effect reported in the Lancet study, augmented dose CRRT is likely too become the standard of treatment, saving 250-300 lives/year in Australia and 15,000 lives/year worldwide.

Trial Design - The proposed study will compare an "augmented" CRRT regimen to deliver an effluent rate of 40 ml/kg/hr compared to "normal" CRRT at an effluent rate of 25ml/kg/hr in ICU patients with severe ARF.

Subject Participation - 90 days

Rationale for Number of Subjects - Assuming a 90-day mortality rate of 60% in our control group the study of 1,500 patients will have 90% power of detecting an 8.5% absolute reduction from a 90-day mortality of 60% in the control group to 51.5% in the intervention group (P<0.05).

Approximate duration of Study - 36 months

Study Objective(s)

Primary - The primary study outcome is death from all causes at 90 days after randomisation.

Secondary

  • Death within the in the intensive care unit.
  • Death within 28 days of randomisation.
  • Death prior to hospital discharge.
  • Length of ICU stay.
  • Length of hospital stay.
  • The need for and duration of other organ support (inotropic/vasopressor support and positive pressure ventilation).
  • CRRT-free days.
  • Dialysis-independent survival.

Criteria for Inclusion

  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 at least ONE of the following clinical criteria for initiating CRRT:

    1. Oliguria (urine output < 100ml/6hr) that has been unresponsive to fluid resuscitation measures.
    2. Hyperkalemia ([K+] > 6.5 mmol/L).
    3. Severe acidemia (pH < 7.2).
    4. Urea > 25 mmol/liter.
    5. Creatinine >300 micromol/L in the setting of ARF.
    6. Clinically significant organ oedema in the setting of ARF (eg: lung).

Criteria for Exclusion

  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 >120kg.
  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.

Approximate Number of Subjects - 1500

Approximate Number of Study Centres - 35 centres distributed in both Australia and New Zealand will participate in the study.

Treatment Administration - Each participant will be randomised to receive CRRT in the technical form of CVVHDF either at an intensity of 25ml/kg/hr of effluent flow(normal CRRT) or 40 ml/kg/hr of effluent flow (augmented CRRT).

Safety Evaluation - Safety for individual patients will be assessed on an ongoing basis by physical examination, including vital signs, outputs from dialysis machine records, laboratory assessments, and monitoring of adverse events. Overall study safety will be ensured by an Independent Data Safety Monitoring Committee, independent from all Trial investigators, which will perform ongoing review of predefined safety parameters and study conduct.

Efficacy Evaluation - Overall survival at 90 days post randomisation

Statistical Analysis - The interim analyses will be conducted when approximately 500 and 1000 patients have completed 90 day follow up, as dictated by the Data Safety Monitoring Committee. The final analysis will occur when outcome data for the target 1500 subjects is available. At interim and final analysis, the baseline and outcome variables will be compared using Students t test, Chi squared and the Mann-Whitney U test as appropriate. Survival analysis will be assessed using the Mantel-Cox test. The final statistical analysis will be performed according to a pre-determined statistical analysis plan (Critical Care and Resuscitation, 2009 in press).

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Acute Renal Failure
Procedure: "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.
  • Experimental: Higher intensity CRRT regimen
    Intervention: Procedure: "augmented" CRRT regimen
  • Active Comparator: Lower intensity CRRT regimen
    Intervention: Procedure: "augmented" CRRT regimen

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1508
January 2009
October 2008   (final data collection date for primary outcome measure)

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).

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Australia
 
NCT00221013
GI-RE-ARF001-40-R, 352550
Yes
Project Manager, The George Institute
The George Institute
ANZICS Clinical Trials Group
Study Chair: Prof Rinaldo Bellomo, MD Austin Hospital, Melbourne Australia
Principal Investigator: Alan Cass, MD The George Institute
Principal Investigator: Simon Finfer, MD Royal North Shore Hospital
Principal Investigator: Carlos Scheinkestel, MD The Alfred
Principal Investigator: Robyn Norton, MD The George Institute
Principal Investigator: John Myburgh, MD St George Hospital (Sydney)
Principal Investigator: Louise Cole, MD Nepean Blue Mountains Local Health District
Principal Investigator: Martin Gallagher, MD The George Institute
Principal Investigator: Shay McGuinness, MD Auckland City Hospital CVICU
Principal Investigator: Colin McArthur, MD Auckland City Hospital DCCM
The George Institute
February 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP