Super High-Flux - High Volume Dialysis in Sepsis-Induced Acute Renal Failure

This study has been completed.
Sponsor:
Information provided by:
Austin Health
ClinicalTrials.gov Identifier:
NCT00333593
First received: June 5, 2006
Last updated: December 26, 2006
Last verified: December 2006
  Purpose

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).


Condition Intervention Phase
Sepsis
Acute Renal Failure
Device: Large pore dialyser
Device: Standard dialyser
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Randomized, Cross Over Study Comparing Standard Hemodialysis to Hemodialysis With a Novel Polyamide Membrane (P2SH) in Patients With Sepsis and Acute Renal Failure

Resource links provided by NLM:


Further study details as provided by Austin Health:

Primary Outcome Measures:
  • The primary outcome measure for this study is the relative change in plasma IL-6 levels.

Secondary Outcome Measures:
  • The secondary outcome is the clearance and the absolute change in the levels of IL-6 and other cytokines.
  • The other secondary outcome is the change in noradrenaline dose required to maintain baseline mean blood pressure (typically 70 mmHg)
  • change in the levels of other cytokines.

Estimated Enrollment: 10
Study Start Date: June 2006
Estimated Study Completion Date: November 2006
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00333593

Locations
Australia, Victoria
Austin Hospital
Melbourne, Victoria, Australia, 3084
Sponsors and Collaborators
Austin Health
Investigators
Principal Investigator: Rinaldo Bellomo, MD, FRACP Austin Health
  More Information

No publications provided by Austin Health

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00333593     History of Changes
Other Study ID Numbers: H2003/01440
Study First Received: June 5, 2006
Last Updated: December 26, 2006
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Austin Health:
Dialysis
Large pore dialyser
Cytokines
Noradrenaline

Additional relevant MeSH terms:
Acute Kidney Injury
Renal Insufficiency
Sepsis
Toxemia
Kidney Diseases
Urologic Diseases
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on July 28, 2014