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

Acute Renal Failure Clinical Trial

Official 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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00221013
• Other study ID #: GI-RE-ARF001-40-R
• Secondary ID: 352550
• Status: Completed
• Phase: Phase 4
• First received: September 14, 2005
• Last updated: February 25, 2009
• Start date: November 2005
• Est. completion date: January 2009

Study information

• Verified date: February 2009
• Source: The George Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: National Health and Medical Research Council
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1508
• Est. completion date: January 2009
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Renal Failure
• Renal Insufficiency

Intervention

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.

Locations

Country	Name	City	State
Australia	The Austin Hopsital	Heidelberg	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
The George Institute	ANZICS Clinical Trials Group

Country where clinical trial is conducted

Australia, 

References & Publications (2)

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death from all causes at 90 days after randomisation.		Within 90 days after randomisation	No
Secondary	Death within the in the intensive care unit.		0 to 90 days	No
Secondary	Death within 28 days of randomisation.		Within 28 days of randomisation.	No
Secondary	Death prior to hospital discharge.		0 to 90 days	No
Secondary	Length of ICU stay.		0 to 90 days	No
Secondary	Length of hospital stay.		0 to 90 days	No
Secondary	The need for and duration of other organ support (inotropic/vasopressor support and positive pressure ventilation).		0 to 90 days	No
Secondary	CRRT-free days.		0 to 90 days	No
Secondary	Dialysis-independent survival.		0 to 90 days	No

External Links

•   Renal Study Website.