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

This study has been terminated.
(based on interim analysis statistical significance in primary endpoint cannot be achieved with planned sample size, no safety concerns)
Sponsor:
Information provided by:
Gambro Dialysatoren GmbH
ClinicalTrials.gov Identifier:
NCT00875888
First received: January 9, 2009
Last updated: January 26, 2010
Last verified: January 2010
  Purpose

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 Intervention
Systemic Inflammatory Response Syndrome
Kidney Failure, Acute
Device: continuous venovenous hemodialysis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Gambro Dialysatoren GmbH:

Primary Outcome Measures:
  • Dosage of vasopressors [ Time Frame: day 1 to day 5 ] [ Designated as safety issue: No ]
  • Mean arterial pressure [ Time Frame: day before inclusion and day 1 to day 5 ] [ Designated as safety issue: No ]
  • Heart rate [ Time Frame: day before inclusion and day 1 to day 5 ] [ Designated as safety issue: No ]
  • Central venous pressure [ Time Frame: day before inclusion and day 1 to day 5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Sequential organ failure assessment (SOFA) score [ Time Frame: at ICU admission, at inclusion and day 1 to day 5 ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Length of need for catecholamine application [ Time Frame: 28 days follow up ] [ Designated as safety issue: No ]
  • Length of need for mechanical ventilation [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Length of need for renal replacement therapy [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Length of stay in intensive care unit (ICU) [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: February 2004
Study Completion Date: June 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Name: continuous venovenous hemodialysis
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.
Other Name: continuous venovenous hemodialysis

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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: NCT00875888

Locations
Austria
Leopold Franzens Universität Innsbruck
Innsbruck, Austria, 6020
Germany
Medizinische Klinik mit Schwerpunkt Nephrologie Charite, Campus Mitte
Berlin, Germany, 10117
Charité-Virchow Klinik
Berlin, Germany, 13353
Universitätsklinikum Tübingen
Tübingen, Germany, 72076
Sponsors and Collaborators
Gambro Dialysatoren GmbH
Investigators
Study Director: Werner Beck, Dr. Gambro Dialysatoren GmbH
  More Information

Publications:

Responsible Party: Werner Beck, Gambro Dialysatoren GmbH
ClinicalTrials.gov Identifier: NCT00875888     History of Changes
Other Study ID Numbers: 0000050, ISRCTN77656437
Study First Received: January 9, 2009
Last Updated: January 26, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Austria: Agency for Health and Food Safety

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

ClinicalTrials.gov processed this record on September 14, 2014