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

Shock Clinical Trial

Official title:

Pilot Randomised Controlled Study Comparing The Effect of High Cut-off Point Haemofiltration With Standard Haemofiltration In Patients With Acute Renal Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00912184
• Other study ID #: High cut-off trial
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 1, 2009
• Last updated: January 26, 2012
• Start date: May 2009
• Est. completion date: January 2012

Study information

• Verified date: January 2012
• Source: Austin Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: January 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Kidney Injury
• Kidney Failure, Acute
• Renal Insufficiency
• Shock

Intervention

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
• 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

Locations

Country	Name	City	State
Australia	Austin Hospital	Heidelberg	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Austin Health

Country where clinical trial is conducted

Australia, 

References & Publications (17)

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. — View Citation

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

Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med. 1996 Jul;24(7):1125-8. — View Citation

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. — View Citation

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. — View Citation

Dinarello CA. Proinflammatory cytokines. Chest. 2000 Aug;118(2):503-8. Review. — View Citation

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. — View Citation

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

Hack CE, Aarden LA, Thijs LG. Role of cytokines in sepsis. Adv Immunol. 1997;66:101-95. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med. 1993 May 20;328(20):1471-7. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome measure for this study is noradrenaline free time in the first week after randomization		24 months	No
Secondary	The change in the levels of each of three key cytokines; IL-1, IL-6 and IL-10		24 months	No