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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00333593




Registration number
NCT00333593
Ethics application status
Date submitted
5/06/2006
Date registered
6/06/2006
Date last updated
27/12/2006

Titles & IDs
Public title
Super High-Flux - High Volume Dialysis in Sepsis-Induced Acute Renal Failure
Scientific title
Randomized, Cross Over Study Comparing Standard Hemodialysis to Hemodialysis With a Novel Polyamide Membrane (P2SH) in Patients With Sepsis and Acute Renal Failure
Secondary ID [1] 0 0
H2003/01440
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis 0 0
Acute Renal Failure 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Injuries and Accidents 0 0 0 0
Poisoning
Blood 0 0 0 0
Other blood disorders
Infection 0 0 0 0
Other infectious diseases
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
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The primary outcome measure for this study is the relative change in plasma IL-6 levels.
Timepoint [1] 0 0
Secondary outcome [1] 0 0
The secondary outcome is the clearance and the absolute change in the levels of IL-6 and other cytokines.
Timepoint [1] 0 0
Secondary outcome [2] 0 0
The other secondary outcome is the change in noradrenaline dose required to maintain baseline mean blood pressure (typically 70 mmHg)
Timepoint [2] 0 0
Secondary outcome [3] 0 0
change in the levels of other cytokines.
Timepoint [3] 0 0

Eligibility
Key inclusion criteria
* All patients who fulfil the consensus criteria for sepsis (21) and recently proposed criteria for severe ARF (1) are eligible for the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients under 18 years of age.
* Patients who are pregnant or breastfeeding
* Patients with a known allergy to polyamide
* Patients expected to die within 24 hours
* Patients in whom there are limitations on the intensity of therapy

Study design
Purpose of the study
Treatment
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
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
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
1/06/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3084 - Melbourne

Funding & Sponsors
Primary sponsor type
Government body
Name
Austin Health
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Patients within the intensive care unit who have severe infections causing shock and kidney failure have almost a 60% risk of dying despite antibiotic therapy, surgical drainage of the site of infection and intensive care support with fluids, nutrition, mechanical ventilation and continuous artificial kidney support. This persistently high death rate continues to stimulate the development of new approaches to the treatment of septic shock.

Much clinical and molecular biology research suggests that these patients die because of an uncontrolled immune system's response to infection. This response involves the production of several substances (so called "humoral mediators"), which enter the blood stream and affect the patient's organs ability to function and the patient's ability to kill germs. These substances may potentially be removed by new artificial filters similar to those currently used during continuous hemofiltration (the type of artificial kidney support used in intensive care).

Recent investigations by ourselves and others, however, have made the following findings:

1. Standard filters currently used in intensive care are ineffective in removing large amounts of these "humoral mediators" because the holes in the filter are too small to allow all of them to pass through
2. The standard filters currently used in intensive care are also ineffective in removing large amounts of these "humoral mediators" because the standard filtration flow through the membrane is less than 100 ml/min
3. When the filtration flow through the membrane is increased to above 100ml/min, patients require a lesser dose of drugs to support their blood pressure which is an indirect sign that the filters are clearing some of the "humoral mediators"
4. Even when the blood flow through standard filters is increased to above 100ml/min, there is still not optimal clearing of "humoral mediators" It is possible, however, that, using a different filter membrane with bigger holes in it, would make it easier to clear the blood of these "humoral mediators". It is thought that this would be noticeable clinically in the amount of drugs required to support blood pressure.

A filter that has these bigger holes is now available. It is made of the same material as the standard filters that are currently used in the intensive care unit, only the holes have been made bigger to allow these "humoral mediators" to be removed from the blood. This polyamide filter is made of synthetic semipermeable material. This material is highly compatible with human blood. This modified polyamide filter is made of exactly the same compatible material but the holes in the material are slightly larger through a minor modification of the manufacturing process.

This larger hole filter has now been used in preliminary studies in humans and has been found to reduce the blood levels of some "humoral mediators". Laboratory studies conducted by ourselves showed that this new filter can achieve the highest reported clearance of some of the "humoral mediators" with minimal effect on useful proteins in blood such as albumin during hemodialysis. This loss is very small and unlikely to contribute to any detectable clinical changes.

We, therefore, now propose to study the effect of using new large hole filters with hemodialysis in patients with severe infections and acute kidney failure.

We wish to compare the effect of this new therapy to that of standard filters. The new therapy will be considered to be effective if it lowers the amount of drugs used to support blood pressure and if it lowers the blood levels of some "humoral mediators" more than standard therapy. We will also monitor blood levels of important components of blood such as albumin and electrolytes in each group.

This is a pilot study involving only 10 patients who will each receive 4 hours of the standard therapy and 4 hours of the new therapy. Which treatment the patient receives first will be random (like the tossing of a coin). Blood samples will be taken at the start and after 4 hours of each treatment. The waste product of dialysis called spent dialysate will also be collected for the measurement of humoral mediators at the start and after 4 hours of each treatment. The changes in blood pressure and drugs used to support it will be recorded hourly. As patients involved in the study would normally receive hemofiltration because of their kidney failure, all the risks and benefits associated with the procedure would be unchanged. The only risk to patients would come from exposure to a modified membrane and from having two additional spoonfuls of blood taken.

If this new membrane were found to have a major effect on the blood level of "humoral mediators" and on the patients' blood pressure, further studies would then be justified to assess its clinical effects (time in ICU, time in hospital, time on ventilator, duration of organ failure, etc).
Trial website
https://clinicaltrials.gov/study/NCT00333593
Trial related presentations / publications
Haase M, Bellomo R, Baldwin I, Haase-Fielitz A, Fealy N, Davenport P, Morgera S, Goehl H, Storr M, Boyce N, Neumayer HH. Hemodialysis membrane with a high-molecular-weight cutoff and cytokine levels in sepsis complicated by acute renal failure: a phase 1 randomized trial. Am J Kidney Dis. 2007 Aug;50(2):296-304. doi: 10.1053/j.ajkd.2007.05.003.
Haase M, Bellomo R, Baldwin I, Haase-Fielitz A, Fealy N, Morgera S, Goehl H, Storr M, Boyce N, Neumayer HH. Beta2-microglobulin removal and plasma albumin levels with high cut-off hemodialysis. Int J Artif Organs. 2007 May;30(5):385-92. doi: 10.1177/039139880703000505.
Public notes

Contacts
Principal investigator
Name 0 0
Rinaldo Bellomo, MD, FRACP
Address 0 0
Austin Health
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/NCT00333593