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

February 25, 2009 updated by: The George Institute

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

1508

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • The Austin Hopsital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Higher intensity CRRT regimen
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.
Active Comparator: Lower intensity CRRT regimen
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Death from all causes at 90 days after randomisation.
Time Frame: Within 90 days after randomisation
Within 90 days after randomisation

Secondary Outcome Measures

Outcome Measure
Time Frame
Death within the in the intensive care unit.
Time Frame: 0 to 90 days
0 to 90 days
Death within 28 days of randomisation.
Time Frame: Within 28 days of randomisation.
Within 28 days of randomisation.
Death prior to hospital discharge.
Time Frame: 0 to 90 days
0 to 90 days
Length of ICU stay.
Time Frame: 0 to 90 days
0 to 90 days
Length of hospital stay.
Time Frame: 0 to 90 days
0 to 90 days
The need for and duration of other organ support (inotropic/vasopressor support and positive pressure ventilation).
Time Frame: 0 to 90 days
0 to 90 days
CRRT-free days.
Time Frame: 0 to 90 days
0 to 90 days
Dialysis-independent survival.
Time Frame: 0 to 90 days
0 to 90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The George Institute

Collaborators

ANZICS Clinical Trials Group

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

October 1, 2008

Study Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

September 14, 2005

First Submitted That Met QC Criteria

September 14, 2005

First Posted (Estimate)

September 22, 2005

Study Record Updates

Last Update Posted (Estimate)

February 27, 2009

Last Update Submitted That Met QC Criteria

February 25, 2009

Last Verified

February 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GI-RE-ARF001-40-R
  • 352550

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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