InflammationEXCESSNCT02606799
Extracorporeal Elimination of Cytokines Following Abdominal-thoracic Esophagectomy
A study testing CytoSorb cytokine elimination in people with Inflammation, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.
Trial summary
This study evaluates the effect of extracorporeal removal of inflammatory mediators on the systemic inflammation reaction of patients admitted to the intensive care unit following elective esophagectomy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inflammation
- What is being tested?
- CytoSorb cytokine elimination
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteGermany
- Study dates
- May 2016to Apr 2017
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- abdominal-thoracic esophagectomy with radical lymphadenectomy
- post operative admission to ICU
- age >= 18 yrs
- written informed consent
Who cannot join
- Participation in another interventional trial
- pregnancy or lactation
- systemic medication with high dose steroids and/or immunosuppressants and/or radiotherapy during the last 3 months
- known diseases of the immune system (benign and malign)
- contraindications for extracorporeal therapy
- Thrombocytopenia < 50*10^9/l
- therapy limitations (DNR), moribund status
- missing informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Extracorporeal Elimination of Cytokines Following Abdominal-thoracic Esophagectomy - a Randomized Study (EXCESS)
This study evaluates the effect of extracorporeal removal of inflammatory mediators on the systemic inflammation reaction of patients admitted to the intensive care unit following elective esophagectomy. Half of the participants will be treated with an adsorption device (CytoSorbents Adsorber), while the other half will be treated according to standard care. Significant reductions of interleukin-6 plasma concentration, SOFA score and catecholamine dosage in the intervention group are expected.
Read the detailed description
Radical esophagectomy combined with extensive lymphadenectomy for esophageal cancer is one of the most invasive surgical procedures. Even with progress made in surgical technique and postoperative management the rate of short- and long term complications remains high. The surgical trauma invariably causes liberation and activation of inflammatory mediators and danger associated molecular patterns, which in turn result in a pronounced systemic inflammatory reaction, leading to multiorgan dysfunction including adult respiratory distress syndrome (ARDS) in many patients. The subsequent counter regulation of the immune system induces immune paralysis, which is followed by infectious complications and increases the probability of severe sepsis. Moreover, severe systemic inflammation causes capillary leakage, resulting in impaired wound healing and endangered anastomoses.
Therefore, it seems that early and effective measures against the excessive production of mediators and cytokines are indicated without impairment of the innate and adaptive immune response as it would be expected with the administration of e.g. steroids. Instead, the removal of an excessive amount of circulating cytokines might be a desirable method having shown its effectivity in the therapy of septic shock in the past.
The aim of this study is to demonstrate the effectiveness of extracorporeal cytokine removal to dampen the systemic inflammatory response following abdominal-thoracic esophagectomy.
- Conditions
- Inflammation
- Being tested
- CytoSorb cytokine elimination
- Keywords
- Esophagectomy Inflammation Hemoperfusion Cytokines
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytoSorb cytokine eliminationDevice
Also called hemadsorption
Hemoperfusion using continuous veno-venous hemofiltration (citrate regional anticoagulation) with CytoSorb cytokine elimination over a period of 48h immediately following admission to the intensive care unit
| Study group | Role | What they receive |
|---|---|---|
| Standard Care | No intervention | intensive care therapy according to international standards and following local SOPs, including fluid therapy, mechanical ventilation, catecholamine therapy and other pharmacotherapy as required |
| CytoSorb | Experimental | all of the above, plus extracorporeal hemadsorption therapy (CytoSorbents Adsorber cartridge) using continuous veno-venous hemofiltration (citrate anticoagulation) CytoSorb cytokine elimination Receives: Device: CytoSorb cytokine elimination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of interleukin-6 plasma levels
Change of interleukin-6 plasma levels
Measured: 72 hours
Secondary outcomes (3)
Change in SOFA Score
decrease of >= 2 score points in the intervention group
Measured: 120 hours
Change of catecholamine dose
decrease of >= 0.1 µg/kg/min catecholamine dosage to achieve MAP > 65 mmHg in intervention group
Measured: 48 hours
Fluid intake
reduction of fluid intake to maintain MAP > 65 mmHg of >= 1000 ml/24h in intervention group
Measured: 120 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2015 (estimated)
- Study startMay 2016
- Primary completionApr 2017
- Study completionApr 2017
Why it stopped: No further recruitment possible due to changed conditions
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 InflammationStudies of the same condition, open and under way.
- More trials run by Universitätsklinikum Hamburg-EppendorfThe sponsor's other registered studies.
- 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Collaborators
- CytoSorbents, Inc
- Responsible party
- Sponsor
- Investigators
- Axel Nierhaus, MD, Principal investigator, University Medical Center Hamburg-Eppendorf, Dep. of Critical Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02606799
- Sponsor's protocol ID
- KIM_CS_001
- Acronym
- EXCESS
- Status last verified
- Jun 2022
- First submitted
- 1 Oct 2015
- Last updated
- 1 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Panagiotou A, Gaiao S, Cruz DN. Extracorporeal therapies in sepsis. J Intensive Care Med. 2013 Sep-Oct;28(5):281-95. doi: 10.1177/0885066611425759. Epub 2011 Oct 25.
PubMed 22027760Bruenger F, Kizner L, Weile J, Morshuis M, Gummert JF. First successful combination of ECMO with cytokine removal therapy in cardiogenic septic shock: a case report. Int J Artif Organs. 2015 Feb;38(2):113-6. doi: 10.5301/ijao.5000382. Epub 2015 Feb 3.
PubMed 25656010Kellum JA, Song M, Venkataraman R. Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding, and improves short-term survival in lethal endotoxemia. Crit Care Med. 2004 Mar;32(3):801-5. doi: 10.1097/01.ccm.0000114997.39857.69.
PubMed 15090965Basu R, Pathak S, Goyal J, Chaudhry R, Goel RB, Barwal A. Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study. Indian J Crit Care Med. 2014 Dec;18(12):822-4. doi: 10.4103/0972-5229.146321.
PubMed 25538418Mitzner SR, Gloger M, Henschel J, Koball S. Improvement of hemodynamic and inflammatory parameters by combined hemoadsorption and hemodiafiltration in septic shock: a case report. Blood Purif. 2013;35(4):314-5. doi: 10.1159/000351206. Epub 2013 Jul 31. No abstract available.
PubMed 23920222
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extracorporeal Elimination of Cytokines Following Abdominal-thoracic Esophagectomy - a Randomized Study (EXCESS)
- ClinicalTrials.gov ID
- NCT02606799
- Acronym / sponsor ID
- EXCESS / KIM_CS_001
- Conditions
- Inflammation
- Keywords
- Esophagectomy Inflammation Hemoperfusion Cytokines
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No further recruitment possible due to changed conditions
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Universitätsklinikum Hamburg-EppendorfUniversity, hospital or other
- Collaborators
- CytoSorbents, Inc
- Study start
- May 2016 (actual)
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 17 Nov 2015 (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 evaluates the effect of extracorporeal removal of inflammatory mediators on the systemic inflammation reaction of patients admitted to the intensive care unit following elective esophagectomy. Half of the participants will be treated with an adsorption device (CytoSorbents Adsorber), while the other half will be treated according to standard care. Significant reductions of interleukin-6 plasma concentration, SOFA score and catecholamine dosage in the intervention group are expected.
Detailed description
Radical esophagectomy combined with extensive lymphadenectomy for esophageal cancer is one of the most invasive surgical procedures. Even with progress made in surgical technique and postoperative management the rate of short- and long term complications remains high. The surgical trauma invariably causes liberation and activation of inflammatory mediators and danger associated molecular patterns, which in turn result in a pronounced systemic inflammatory reaction, leading to multiorgan dysfunction including adult respiratory distress syndrome (ARDS) in many patients. The subsequent counter regulation of the immune system induces immune paralysis, which is followed by infectious complications and increases the probability of severe sepsis. Moreover, severe systemic inflammation causes capillary leakage, resulting in impaired wound healing and endangered anastomoses.
Therefore, it seems that early and effective measures against the excessive production of mediators and cytokines are indicated without impairment of the innate and adaptive immune response as it would be expected with the administration of e.g. steroids. Instead, the removal of an excessive amount of circulating cytokines might be a desirable method having shown its effectivity in the therapy of septic shock in the past.
The aim of this study is to demonstrate the effectiveness of extracorporeal cytokine removal to dampen the systemic inflammatory response following abdominal-thoracic esophagectomy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Care | No intervention | –intensive care therapy according to international standards and following local SOPs, including fluid therapy, mechanical ventilation, catecholamine therapy and other pharmacotherapy as required |
| CytoSorb | Experimental | Device: CytoSorb cytokine eliminationall of the above, plus extracorporeal hemadsorption therapy (CytoSorbents Adsorber cartridge) using continuous veno-venous hemofiltration (citrate anticoagulation) CytoSorb cytokine elimination |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- abdominal-thoracic esophagectomy with radical lymphadenectomy
- post operative admission to ICU
- age >= 18 yrs
- written informed consent
Key exclusion criteria (8 listed)
- Participation in another interventional trial
- pregnancy or lactation
- systemic medication with high dose steroids and/or immunosuppressants and/or radiotherapy during the last 3 months
- known diseases of the immune system (benign and malign)
- contraindications for extracorporeal therapy
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 |
|---|---|---|
| CytoSorb cytokine eliminationAlso: hemadsorptionHemoperfusion using continuous veno-venous hemofiltration (citrate regional anticoagulation) with CytoSorb cytokine elimination over a period of 48h immediately following admission to the intensive care unit | Device | CytoSorb |
Primary outcome
Change of interleukin-6 plasma levels
Time frame: 72 hours
Change of interleukin-6 plasma levels
3 secondary outcomes
Change in SOFA Score
Time frame: 120 hours
Change of catecholamine dose
Time frame: 48 hours
Fluid intake
Time frame: 120 hours
Results and safety
The study was stopped early (reason given: No further recruitment possible due to changed conditions). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2022.
- Background: PubMed 22027760Panagiotou A, Gaiao S, Cruz DN. Extracorporeal therapies in sepsis. J Intensive Care Med. 2013 Sep-Oct;28(5):281-95. doi: 10.1177/0885066611425759. Epub 2011 Oct 25.
- Background: PubMed 25656010Bruenger F, Kizner L, Weile J, Morshuis M, Gummert JF. First successful combination of ECMO with cytokine removal therapy in cardiogenic septic shock: a case report. Int J Artif Organs. 2015 Feb;38(2):113-6. doi: 10.5301/ijao.5000382. Epub 2015 Feb 3.
- Background: PubMed 15090965Kellum JA, Song M, Venkataraman R. Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding, and improves short-term survival in lethal endotoxemia. Crit Care Med. 2004 Mar;32(3):801-5. doi: 10.1097/01.ccm.0000114997.39857.69.
- Background: PubMed 25538418Basu R, Pathak S, Goyal J, Chaudhry R, Goel RB, Barwal A. Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study. Indian J Crit Care Med. 2014 Dec;18(12):822-4. doi: 10.4103/0972-5229.146321.
- Background: PubMed 23920222Mitzner SR, Gloger M, Henschel J, Koball S. Improvement of hemodynamic and inflammatory parameters by combined hemoadsorption and hemodiafiltration in septic shock: a case report. Blood Purif. 2013;35(4):314-5. doi: 10.1159/000351206. Epub 2013 Jul 31. No abstract available.
- technical and scientific informationLink provided by the sponsor.
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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.
Axel Nierhaus, MD principal investigator
University Medical Center Hamburg-Eppendorf, Dep. of Critical Care
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CytoSorb cytokine elimination in people with Inflammation, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.
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 8 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 1 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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: No further recruitment possible due to changed conditions). 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?
Change of interleukin-6 plasma levels (time frame: 72 hours). 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 NCT02606799, 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 1 Jul 2022.