Study Comparing High Cut-off Haemofiltration With Standard Haemofiltration in Acute Renal Failure - Full Text View

Purpose

This trial aims to study the effect of combining continuous and a new polyamide membrane with larger pores in the treatment of critically ill patients with acute renal failure and low blood pressure (shock) requiring noradrenaline. The investigators wish to compare the clinical effect of this new therapy to that of haemofiltration with a standard membrane.

Condition	Intervention	Phase
Kidney Failure, Acute Shock	Device: Standard polyamide high flux membrane Device: High cut-off (super high flux) polyamide membrane	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Pilot Randomised Controlled Study Comparing The Effect of High Cut-off Point Haemofiltration With Standard Haemofiltration In Patients With Acute Renal Failure

Resource links provided by NLM:

MedlinePlus related topics: Shock

U.S. FDA Resources

Further study details as provided by Austin Health:

Primary Outcome Measures:

The primary outcome measure for this study is noradrenaline free time in the first week after randomization [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The change in the levels of each of three key cytokines; IL-1, IL-6 and IL-10 [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Enrollment:	76
Study Start Date:	May 2009
Study Completion Date:	January 2012
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 CVVH with high cut-off polyamide membrane (P2SH) using standard continuous veno-venous hemofiltration (CVVH) settings	Device: High cut-off (super high flux) polyamide membrane CVVH with standard haemofiltration settings; blood flow 200 ml/min, ultrafiltrate 25 ml/kg/hour, anticoagulation as clinically indicated, bicarbonate-buffered replacement fluid Other Names: P2SH Super high flux membrane
Active Comparator: 2 CVVH using standard high flux membrane with standard CVVH settings	Device: Standard polyamide high flux membrane Standard haemofiltration; CVVH; blood flow 200 ml/min, ultrafiltrate 25 ml/kg/hr, anticoagulation as clinically indicated, bicarbonate buffered replacement fluid Other Name: High flux membrane

Detailed Description:

During acute renal failure, small and middle molecular-weight toxins accumulate. These molecules are difficult to remove by standard haemofiltration. Accordingly, they accumulate and contribute to morbidity in long-term dialysis patients. Molecules such as cytokines have been shown to play a central pathogenic role in critical illness. In critically ill acute renal failure patients, they accumulate in serum and likely contribute to much morbidity (fever, low blood pressure, myocardial dysfunction, renal failure itself etc.) Therefore, the removal of cytokines appears desirable. Although different approaches have been undertaken, all have had limited success due to complexity, limited efficacy or uncertain clinical response [10-15].

It is possible that in using a different and more porous membrane, the removal of cytokines would be much more efficient and that clinical benefits of blood purification would, therefore, be greater.

A membrane of this kind is now available. It is a modification (moderate increase in pore size) of another standard material called polyamide, which has already been used in millions of people for dialysis and haemofiltration. The increased pore size of these new membranes is directed at a more effective removal of middle molecular-weight toxins such as cytokines.

Eligibility

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

Criteria

Inclusion Criteria:

The treating clinician believes that the patient requires haemofiltration for acute renal failure
The patient is on noradrenaline infusion for haemodynamic support
The patient was commenced on noradrenaline or haemofiltration within the last 12 hours
The clinician is uncertain about the balance of benefits and risks likely to be conferred by treatment with different membranes
The treating clinicians anticipate treating the patient with haemofiltration for at least 72 hours
Informed consent has been obtained
The patient fulfils ONE of the following clinical criteria for initiating haemofiltration:
Oliguria (urine output < 100 ml/6 hr) 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 mmol/L
Clinically significant organ oedema in the setting of ARF (e.g., lung)

Exclusion Criteria:

Patient age is < 18 years
Death is imminent (< 24 hours)
There is a strong likelihood that the study treatment would not be continued in accordance with the study protocol
The patient has been treated with haemofiltration or other dialysis previously during the same hospital admission
The patient was on maintenance dialysis prior to the current hospitalisation
Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study
The patient is pregnant or is breastfeeding
The patient has previously been enrolled in this study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00912184

Locations

Australia, Victoria
Austin Hospital
Heidelberg, Victoria, Australia, 3084

Sponsors and Collaborators

Austin Health

Investigators

Principal Investigator:

Rafidah Atan, MBBS, FANZCA

Austin Health

More Information

Publications:

Ronco C, Tetta C, Mariano F, Wratten ML, Bonello M, Bordoni V, Cardona X, Inguaggiato P, Pilotto L, d'Intini V, Bellomo R. Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis. Artif Organs. 2003 Sep;27(9):792-801. Review.

Marshall JC. Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome. Crit Care Med. 2001 Jul;29(7 Suppl):S99-106. Review.

Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med. 1993 May 20;328(20):1471-7. Review. No abstract available.

Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med. 1996 Jul;24(7):1125-8. No abstract available.

Pinsky MR, Vincent JL, Deviere J, Alegre M, Kahn RJ, Dupont E. Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest. 1993 Feb;103(2):565-75.

Hack CE, Aarden LA, Thijs LG: Role of cytokines in sepsis. Adv Immunol 1997; 66:101-195

Dinarello CA: Proinflammatory cytokines. Chest 2000; 118:503-508

Glauser MP. The inflammatory cytokines. New developments in the pathophysiology and treatment of septic shock. Drugs. 1996;52 Suppl 2:9-17. Review.

Bellomo R, Tipping P, Boyce N. Continuous veno-venous hemofiltration with dialysis removes cytokines from the circulation of septic patients. Crit Care Med. 1993 Apr;21(4):522-6.

Bellomo R. Continuous hemofiltration as blood purification in sepsis. New Horiz. 1995 Nov;3(4):732-7. Review.

De Vriese AS, Colardyn FA, Philippé JJ, Vanholder RC, De Sutter JH, Lameire NH. Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol. 1999 Apr;10(4):846-53.

Hoffmann JN, Hartl WH, Deppisch R, Faist E, Jochum M, Inthorn D. Hemofiltration in human sepsis: evidence for elimination of immunomodulatory substances. Kidney Int. 1995 Nov;48(5):1563-70.

Gasche Y, Pascual M, Suter PM, Favre H, Chevrolet JC, Schifferli JA. Complement depletion during haemofiltration with polyacrilonitrile membranes. Nephrol Dial Transplant. 1996 Jan;11(1):117-9.

Kellum JA, Johnson JP, Kramer D, Palevsky P, Brady JJ, Pinsky MR. Diffusive vs. convective therapy: effects on mediators of inflammation in patient with severe systemic inflammatory response syndrome. Crit Care Med. 1998 Dec;26(12):1995-2000.

Cole L, Bellomo R, Hart G, Journois D, Davenport P, Tipping P, Ronco C. A phase II randomized, controlled trial of continuous hemofiltration in sepsis. Crit Care Med. 2002 Jan;30(1):100-6.

Lee WC, Uchino S, Fealy N, Baldwin I, Panagiotopoulos S, Goehl H, Morgera S, Neumayer HH, Bellomo R. Super high flux hemodialysis at high dialysate flows: an ex vivo assessment. Int J Artif Organs. 2004 Jan;27(1):24-8.

Uchino S, Bellomo R, Morimatsu H, Goldsmith D, Davenport P, Cole L, Baldwin I, Panagiotopoulos S, Tipping P, Morgera S, Neumayer HH, Goehl H. Cytokine dialysis: an ex vivo study. ASAIO J. 2002 Nov-Dec;48(6):650-3.

Responsible Party:	Rafidah Atan, PhD student, Austin Health
ClinicalTrials.gov Identifier:	NCT00912184 History of Changes
Other Study ID Numbers:	High cut-off trial
Study First Received:	June 1, 2009
Last Updated:	January 26, 2012
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Austin Health:

Kidney failure, acute
Shock
Toxins, biological
Hemofiltration
High cut off/super high flux membranes

Additional relevant MeSH terms:

Acute Kidney Injury
Renal Insufficiency
Shock

Kidney Diseases
Urologic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on June 17, 2013