HICOSS: High Cut-Off Continuous Veno-venous Hemodialysis (CVVHD) in Patients Treated for Acute Renal Failure After Systemic Inflammatory Response Syndrome (SIRS)/Septic Shock

• Sponsor: Baxter Healthcare Corporation (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00875888
• Collaborator: Gambro Dialysatoren GmbH (Industry)
• Enrollment: 80
• Locations: 4
• Arms: 2
• Duration (Months): 64
• Patients Per Site: 20
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will assess the influence of the High Cut-Off (HCO) CVVHD treatment on the disease progression in septic patients. The primary aim of the study is to evaluate whether HCO CVVHD leads to a significant improvement of the hemodynamic status (mean arterial pressure, vasopressor requirements) in septic patients in comparison to CVVHD treatment with conventional high-flux filters. For the HCO-group the investigators expect a 50% lower dosage of vasopressors needed to maintain an adequate organ perfusion.

Condition or Disease	Intervention/Treatment	Phase
Systemic Inflammatory Response Syndrome; Kidney Failure, Acute	Device: continuous venovenous hemodialysis	N/A

Detailed Description

Severe sepsis is a devastating disorder that results from a complex host response to insult after infection. Despite advances in intensive care technologies sepsis remains an important and life-threatening problem. Sepsis is the most common cause of death in the intensive care unit.

Local or systemic release of bacteria-derived compounds, leading to the production of proinflammatory cytokines, induce systemic inflammatory reactions in septic patients. Continuous renal replacement therapies (CRRT) such as hemodialysis (CVVHD), hemofiltration (CVVH) or hemodiafiltration (CVVHDF) with conventional high-flux membranes allow to control fluid and electrolyte balance, and to improve the hemodynamic status of the patients. However, conventional high flux membranes have a limited permeability for sepsis-associated mediators with molecular weights in the range of 15.000 to 60.000 Da.

A promising approach to enhance the mediator removal is to use membranes having larger pores and permeability characteristics than those currently used in CRRT.

For that purpose a High Cut-Off (HCO) membrane has been developed and is manufactured by Gambro Research.After demonstrating the safety as well as the cytokine removal effectiveness in a clinical pilot study this study will assess the influence of the HCO treatment on the disease progression in septic patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: High Cut-off Continuous Venovenous Hemodialysis (CVVHD) to Improve Hemodynamic Stability and Organ Function Scores in Patients Treated for Acute Renal Failure After Systemic Inflammatory Response Syndrome (SIRS)/Septic Shock
• Study Start Date: Feb 1, 2004
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HCO High cut-off filters HCO1100	Device: continuous venovenous hemodialysis; dialysate flow rate 35 ml/h/kg. Blood flow rate should be aimed at 200 ml/min, but not less than 150 ml/min. Bicarbonate- or lactate-buffered solutions will be used as dialysis fluids. Study dialyzers will be changed routinely every 24 h or earlier if the filter is obstructed by clotting.
Active Comparator: control conventional high-flux filters	Device: continuous venovenous hemodialysis; dialysate flow rate 35 ml/h/kg. Blood flow rate should be aimed at 200 ml/min, but not less than 150 ml/min. Bicarbonate- or lactate-buffered solutions will be used as dialysis fluids. Study dialyzers will be changed routinely every 24 h or earlier if the filter is obstructed by clotting.

Outcome Measures

Primary Outcome Measures

1. Dosage of vasopressors [day 1 to day 5]

2. Mean arterial pressure [day before inclusion and day 1 to day 5]

3. Heart rate [day before inclusion and day 1 to day 5]

4. Central venous pressure [day before inclusion and day 1 to day 5]

Secondary Outcome Measures

1. Sequential organ failure assessment (SOFA) score [at ICU admission, at inclusion and day 1 to day 5]

2. Survival [28 days]

3. Length of need for catecholamine application [28 days follow up]

4. Length of need for mechanical ventilation [28 days]

5. Length of need for renal replacement therapy [28 days]

6. Length of stay in intensive care unit (ICU) [28 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Fulfilling at least two of the SIRS criteria as defined by the American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM) Consensus Conference

2. Having signs of renal dysfunction

3. Requirement for catecholamine administration (norepinephrine or others)

4. Acute Physiology And Chronic Health Evaluation (APACHE II) score at enrolment greater than or equal to 19 and less than or equal to 30

Exclusion Criteria:

1. Lack of written informed consent from patients or a legally authorized surrogate

2. Duration of septic shock greater than 4 days

3. Hypoproteinemia (characterized by serum albumin less than 18 g/l)

4. End stage renal failure

5. Known active malignancy

6. Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

7. Age younger than 18 years or older than 80 years

8. Known pregnancy

9. Immunosuppression after transplantation

10. Participation in another clinical study

11. Renal replacement therapy greater than 24 hours before randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leopold Franzens Universität Innsbruck	Innsbruck		Austria	6020
2	Medizinische Klinik mit Schwerpunkt Nephrologie Charite, Campus Mitte	Berlin		Germany	10117
3	Charité-Virchow Klinik	Berlin		Germany	13353
4	Universitätsklinikum Tübingen	Tübingen		Germany	72076

Sponsors and Collaborators

• Baxter Healthcare Corporation
• Gambro Dialysatoren GmbH

Investigators

• Study Director: Werner Beck, Dr., Gambro Dialysatoren GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

• Morgera S, Haase M, Kuss T, Vargas-Hein O, Zuckermann-Becker H, Melzer C, Krieg H, Wegner B, Bellomo R, Neumayer HH. Pilot study on the effects of high cutoff hemofiltration on the need for norepinephrine in septic patients with acute renal failure. Crit Care Med. 2006 Aug;34(8):2099-104.
• Morgera S, Haase M, Rocktäschel J, Böhler T, Vargas-Hein O, Melzer C, Krausch D, Kox WJ, Baumann G, Beck W, Göhl H, Neumayer HH. Intermittent high-permeability hemofiltration modulates inflammatory response in septic patients with multiorgan failure. Nephron Clin Pract. 2003;94(3):c75-80.
• Morgera S, Haase M, Rocktäschel J, Böhler T, von Heymann C, Vargas-Hein O, Krausch D, Zuckermann-Becker H, Müller JM, Kox WJ, Neumayer HH. High permeability haemofiltration improves peripheral blood mononuclear cell proliferation in septic patients with acute renal failure. Nephrol Dial Transplant. 2003 Dec;18(12):2570-6.
• Morgera S, Rocktäschel J, Haase M, Lehmann C, von Heymann C, Ziemer S, Priem F, Hocher B, Göhl H, Kox WJ, Buder HW, Neumayer HH. Intermittent high permeability hemofiltration in septic patients with acute renal failure. Intensive Care Med. 2003 Nov;29(11):1989-95. Epub 2003 Sep 3.
• Morgera S, Slowinski T, Melzer C, Sobottke V, Vargas-Hein O, Volk T, Zuckermann-Becker H, Wegner B, Müller JM, Baumann G, Kox WJ, Bellomo R, Neumayer HH. Renal replacement therapy with high-cutoff hemofilters: Impact of convection and diffusion on cytokine clearances and protein status. Am J Kidney Dis. 2004 Mar;43(3):444-53.

• Responsible Party: Baxter Healthcare Corporation
• ClinicalTrials.gov Identifier: NCT00875888
• Other Study ID Numbers: 0000050; ISRCTN77656437
• First Posted: Apr 6, 2009
• Last Update Posted: Mar 7, 2018
• Last Verified: Mar 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Renal Insufficiency; Acute Kidney Injury; Syndrome; Systemic Inflammatory Response Syndrome

Study Results

No Results Posted as of Mar 7, 2018