Systemic Inflammatory Response SyndromeHICOSSNCT00875888
High Cut-Off Continuous Veno-venous Hemodialysis (CVVHD) in Patients Treated for Acute Renal Failure After Systemic Inflammatory Response Syndrome (SIRS)/Septic Shock
A study testing continuous venovenous hemodialysis in people with Systemic Inflammatory Response Syndrome and Kidney Failure, Acute, run by Vantive Health LLC at 4 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Systemic Inflammatory Response Syndrome, Kidney Failure, Acute
- What is being tested?
- continuous venovenous hemodialysis
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Feb 2004to Jun 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Having signs of renal dysfunction
- Requirement for catecholamine administration (norepinephrine or others)
- Acute Physiology And Chronic Health Evaluation (APACHE II) score at enrolment greater than or equal to 19 and less than or equal to 30
Who cannot join
- Lack of written informed consent from patients or a legally authorized surrogate
- Duration of septic shock greater than 4 days
- Hypoproteinemia (characterized by serum albumin less than 18 g/l)
- End stage renal failure
- Known active malignancy
- Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
Show all 11Show fewer
- Age younger than 18 years or older than 80 years
- Known pregnancy
- Immunosuppression after transplantation
- Participation in another clinical study
- Renal replacement therapy greater than 24 hours before randomization
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Germany3 sites
Medizinische Klinik mit Schwerpunkt Nephrologie Charite, Campus Mitte
Berlin, 10117
Charité-Virchow Klinik
Berlin, 13353
Universitätsklinikum Tübingen
Tübingen, 72076
About this study
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
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.
Read the 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.
- Being tested
- continuous venovenous hemodialysis
- Medical subject headings
- Systemic Inflammatory Response Syndrome, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
continuous venovenous hemodialysisDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| HCO | Experimental | High cut-off filters HCO1100 Receives: Device: continuous venovenous hemodialysis |
| control | Active comparator | conventional high-flux filters Receives: Device: continuous venovenous hemodialysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dosage of vasopressors
Measured: day 1 to day 5
Mean arterial pressure
Measured: day before inclusion and day 1 to day 5
Heart rate
Measured: day before inclusion and day 1 to day 5
Central venous pressure
Measured: day before inclusion and day 1 to day 5
Secondary outcomes (6)
Sequential organ failure assessment (SOFA) score
Measured: at ICU admission, at inclusion and day 1 to day 5
Survival
Measured: 28 days
Length of need for catecholamine application
Measured: 28 days follow up
Length of need for mechanical ventilation
Measured: 28 days
Length of need for renal replacement therapy
Measured: 28 days
Length of stay in intensive care unit (ICU)
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2009 (estimated)
- Study startFeb 2004
- Primary completionJun 2009
- Study completionJun 2009
Why it stopped: based on interim analysis statistical significance in primary endpoint cannot be achieved with planned sample size, no safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Systemic Inflammatory Response SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vantive Health LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Gambro Dialysatoren GmbH, Baxter Healthcare Corporation
- Responsible party
- Sponsor
- Investigators
- Werner Beck, Dr., Study director, Gambro Dialysatoren GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00875888
- Sponsor's protocol ID
- 0000050
- Other IDs
- ISRCTN77656437
- Acronym
- HICOSS
- Status last verified
- Mar 2025
- First submitted
- 9 Jan 2009
- Last updated
- 13 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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. doi: 10.1097/01.CCM.0000229147.50592.F9.
PubMed 16763508Morgera S, Haase M, Rocktaschel J, Bohler T, von Heymann C, Vargas-Hein O, Krausch D, Zuckermann-Becker H, Muller 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. doi: 10.1093/ndt/gfg435.
PubMed 14605279Morgera S, Rocktaschel J, Haase M, Lehmann C, von Heymann C, Ziemer S, Priem F, Hocher B, Gohl 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. doi: 10.1007/s00134-003-2003-9. Epub 2003 Sep 3.
PubMed 12955174Morgera S, Haase M, Rocktaschel J, Bohler T, Vargas-Hein O, Melzer C, Krausch D, Kox WJ, Baumann G, Beck W, Gohl H, Neumayer HH. Intermittent high-permeability hemofiltration modulates inflammatory response in septic patients with multiorgan failure. Nephron Clin Pract. 2003;94(3):c75-80. doi: 10.1159/000072024.
PubMed 12902634Morgera S, Slowinski T, Melzer C, Sobottke V, Vargas-Hein O, Volk T, Zuckermann-Becker H, Wegner B, Muller 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. doi: 10.1053/j.ajkd.2003.11.006.
PubMed 14981602
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00875888
- Acronym / sponsor ID
- HICOSS / 0000050
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: based on interim analysis statistical significance in primary endpoint cannot be achieved with planned sample size, no safety concerns
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Vantive Health LLCIndustry (pharma, biotech, devices)
- Collaborators
- Gambro Dialysatoren GmbH, Baxter Healthcare Corporation
- Study start
- Feb 2004
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 6 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HCO | Experimental | Device: continuous venovenous hemodialysisHigh cut-off filters HCO1100 |
| control | Active comparator | Device: continuous venovenous hemodialysisconventional high-flux filters |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
- Having signs of renal dysfunction
- Requirement for catecholamine administration (norepinephrine or others)
- Acute Physiology And Chronic Health Evaluation (APACHE II) score at enrolment greater than or equal to 19 and less than or equal to 30
Key exclusion criteria (11 listed)
- Lack of written informed consent from patients or a legally authorized surrogate
- Duration of septic shock greater than 4 days
- Hypoproteinemia (characterized by serum albumin less than 18 g/l)
- End stage renal failure
- Known active malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| continuous venovenous hemodialysisdialysate 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. | Device | HCO, control |
Primary outcome
Dosage of vasopressors
Time frame: day 1 to day 5
Mean arterial pressure
Time frame: day before inclusion and day 1 to day 5
Heart rate
Time frame: day before inclusion and day 1 to day 5
Central venous pressure
Time frame: day before inclusion and day 1 to day 5
6 secondary outcomes
Sequential organ failure assessment (SOFA) score
Time frame: at ICU admission, at inclusion and day 1 to day 5
Survival
Time frame: 28 days
Length of need for catecholamine application
Time frame: 28 days follow up
Length of need for mechanical ventilation
Time frame: 28 days
Length of need for renal replacement therapy
Time frame: 28 days
Length of stay in intensive care unit (ICU)
Time frame: 28 days
Results and safety
The study was stopped early (reason given: based on interim analysis statistical significance in primary endpoint cannot be achieved with planned sample size, no safety concerns). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2025.
- Background: PubMed 16763508Morgera 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. doi: 10.1097/01.CCM.0000229147.50592.F9.
- Background: PubMed 14605279Morgera S, Haase M, Rocktaschel J, Bohler T, von Heymann C, Vargas-Hein O, Krausch D, Zuckermann-Becker H, Muller 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. doi: 10.1093/ndt/gfg435.
- Background: PubMed 12955174Morgera S, Rocktaschel J, Haase M, Lehmann C, von Heymann C, Ziemer S, Priem F, Hocher B, Gohl 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. doi: 10.1007/s00134-003-2003-9. Epub 2003 Sep 3.
- Background: PubMed 12902634Morgera S, Haase M, Rocktaschel J, Bohler T, Vargas-Hein O, Melzer C, Krausch D, Kox WJ, Baumann G, Beck W, Gohl H, Neumayer HH. Intermittent high-permeability hemofiltration modulates inflammatory response in septic patients with multiorgan failure. Nephron Clin Pract. 2003;94(3):c75-80. doi: 10.1159/000072024.
- Background: PubMed 14981602Morgera S, Slowinski T, Melzer C, Sobottke V, Vargas-Hein O, Volk T, Zuckermann-Becker H, Wegner B, Muller 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. doi: 10.1053/j.ajkd.2003.11.006.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Werner Beck, Dr. study director
Gambro Dialysatoren GmbH
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing continuous venovenous hemodialysis in people with Systemic Inflammatory Response Syndrome and Kidney Failure, Acute, run by Vantive Health LLC at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: based on interim analysis statistical significance in primary endpoint cannot be achieved with planned sample size, no safety concerns). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dosage of vasopressors (time frame: day 1 to day 5). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00875888, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2025.