CoronavirusCYCOVNCT04324528
Cytokine Adsorption in Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation
A study testing vv-ECMO + cytokine adsorption (Cytosorb adsorber) and vv-ECMO only (no cytokine adsorption) in people with Coronavirus and COVID-19, run by Dr. Alexander Supady at 1 site in Germany.
Trial summary
In December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Coronavirus, COVID-19, SARS-CoV Infection
- What is being tested?
- vv-ECMO + cytokine adsorption (Cytosorb adsorber) and vv-ECMO only (no cytokine adsorption)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteGermany
- Study dates
- 27 Mar 2020to 27 Jan 2021
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- SARS-CoV-2-infection with COVID-pneumonia
- vv-ECMO therapy
Who cannot join
- pregnancy, breastfeeding
Trial locations and contacts
1 site in 1 country.
About this study
In December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world.
Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen.
Read more
Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome.
From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients.
Our primary goal is to investigate the efficacy of treatment with a CytoSorb® adsorber in patients with severe COVID-19 disease requiring venous ECMO over 72 hours after initiation of ECMO. The primary endpoint is the reduction of plasma interleukin-6 levels 72 hours after initiation of ECMO support. As secondary endpoints we investigate 30-day survival, vasopressor and volume requirements, lactate in terms of lactate and platelet function. As safety variables, we further investigate the levels of the applied antibiotics (usually ampicillin and sulbactam).
Read the detailed description
In December 2019, a series of unexplained cases of pneumonia in the city of Wuhan in China has come to light. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (first named 2019-nCoV, then SARS-CoV-2). The disease spread rapidly in the city of Wuhan in early 2020 and soon beyond. On 30 January 2020, the Director-General of the World Health Organization (WHO) declared the outbreak a public health emergency of international concern, and on 11 March 2020, the World Health Organization declared the virus a pandemic.
In humans, an infection with the virus can cause respiratory infections and even very severe pneumonia, which often ends fatally, especially in old and previously ill patients. Due to the novelty of the virus, the data basis for therapy is very limited. To date, there are no clinical data for an effective specific therapy, nor is there a vaccination against the virus available, so that therapy, especially intensive care treatment for very severe cases, must concentrate only on supportive treatment of lung failure and other complications.
The virus is very contagious and infection results in a relevant number of deaths. Due to very uncertain data on the spread of the virus in the population, it is difficult to estimate the mortality rate - case mortality is about 4% based on known case numbers.
In reports on the treatment of the first cases in Wuhan (Hubei Province, China) in January 2020, the need for intensive care treatment is described for about a quarter of the inpatient cases, 10-17% had to be ventilated invasively, and venous extracorporeal membrane oxygenation (vv-ECMO) was necessary in 2-4% of the inpatient cases. Patients requiring ECMO have an extremely high mortality rate of 83-100% in the studies described so far.
In severe cases a pronounced release of vasoactive cytokines was repeatedly observed. Excessive release of these vasoactive mediators ("cytokine storm") can result in pronounced vasodilatation and membrane leakage, which can ultimately lead to severe vasoplegic shock that is difficult to control. Ruan et al. and Zhou et al. have identified high interleukin 6 (IL-6) levels as a potential predictor of a fatal outcome when compared between survivors and patients who died of COVID-19 disease.
IL-6 is also an important factor in the pathophysiology of severe septic shock and excessive immune response in hemophagocytic lymphohistiocytosis (HLH) - for both indications has been shown, that the extracorporeal adsorption of IL-6 and other vasoactive substances in a CytoSorb® adsorber (CytoSorbents Corporation, Monmouth Junction, NJ, USA) leads to a significant reduction of these cytokines in the patient blood. Clinical experience and (previously unpublished) data from our monocentric registry study show that cytokine adsorption in a CytoSorb® Adsorber can also be safely integrated into a vv-ECMO system.
The aim of the study is to investigate the influence of extracorporeal cytokine adsorption on humoral inflammation parameters and patient survival under controlled conditions in patients with severe COVID-19 disease requiring extracorporeal membrane oxygenation.
- Conditions
- Coronavirus, COVID-19, SARS-CoV Infection, Respiratory Failure, Cytokine Storm
- Being tested
- vv-ECMO + cytokine adsorption (Cytosorb adsorber), vv-ECMO only (no cytokine adsorption)
- Medical subject headings
- Coronavirus Infections, COVID-19, Severe Acute Respiratory Syndrome, Respiratory Insufficiency, Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vv-ECMO + cytokine adsorption (Cytosorb adsorber)Device
in COVID-19-diseased vv-ECMO patients additional treatment with cytokine adsorption using a Cytosorb adsorber will be randomized (vs. control group)
vv-ECMO only (no cytokine adsorption)Device
COVID-19-diseased treated with vv-ECMO
| Study group | Role | What they receive |
|---|---|---|
| vv-ECMO + cytokine adsorption | Experimental | after indication of treatment with vv-ECMO in acute respiratory failure in COVID-19-disease, patients will additionally receive cytokine adsorption using a Cytosorb adsorber Receives: Device: vv-ECMO + cytokine adsorption (Cytosorb adsorber) |
| control-arm: vv-ECMO (no cytokine adsorption) | Other | treatment with vv-ECMO in acute respiratory failure in COVID-19-disease (standard treatment without additional cytokine adsorption) Receives: Device: vv-ECMO only (no cytokine adsorption) |
What is being measured
The primary outcome is the main question the study is designed to answer.
interleukin-6 (IL-6) level after 72 hours
measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)
Measured: 72 hours
Secondary outcomes (4)
30-day-survival
survival after 30 days
Measured: 72 hours
vasopressor dosage
needed dosage of norepinephrine and other vasopressors
Measured: 72 hours
fluid balance
fluid balance levels during cytokine adsorption
Measured: 72 hours
lactate
serum-lactate levels during cytokine adsorption
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2020
- Study start27 Mar 2020
- Primary completion27 Jan 2021
- Study completion27 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CoronavirusStudies 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
- Single group
- Model description
- randomized controlled trial examining COVID-patients requiring vv-ECMO therapy (+/- cytokine adsorption)
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Alexander Supady
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Alexander Supady, University Hospital Freiburg
- Investigators
- Alexander Supady, Dr., MPH, Principal investigator, University Clinic Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04324528
- Sponsor's protocol ID
- CYCOV
- Acronym
- CYCOV
- Status last verified
- Mar 2021
- First submitted
- 25 Mar 2020
- Last updated
- 15 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Supady A, Weber E, Rieder M, Lother A, Niklaus T, Zahn T, Frech F, Muller S, Kuhl M, Benk C, Maier S, Trummer G, Flugler A, Kruger K, Sekandarzad A, Stachon P, Zotzmann V, Bode C, Biever PM, Staudacher D, Wengenmayer T, Graf E, Duerschmied D. Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial. Lancet Respir Med. 2021 Jul;9(7):755-762. doi: 10.1016/S2213-2600(21)00177-6. Epub 2021 May 14.
PubMed 34000236
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cytokine Adsorption in Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation
- ClinicalTrials.gov ID
- NCT04324528
- Acronym / sponsor ID
- CYCOV / CYCOV
- Conditions
- Coronavirus, COVID-19, SARS-CoV Infection, Respiratory Failure, Cytokine Storm
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Dr. Alexander SupadyUniversity, hospital or other
- Study start
- 27 Mar 2020 (actual)
- Primary completion
- 27 Jan 2021 (actual)
- Study completion
- 27 Jan 2021 (actual)
- First posted
- 27 Mar 2020 (actual)
- 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.
In December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world.
Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen.
Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome.
From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients.
Our primary goal is to investigate the efficacy of treatment with a CytoSorb® adsorber in patients with severe COVID-19 disease requiring venous ECMO over 72 hours after initiation of ECMO. The primary endpoint is the reduction of plasma interleukin-6 levels 72 hours after initiation of ECMO support. As secondary endpoints we investigate 30-day survival, vasopressor and volume requirements, lactate in terms of lactate and platelet function. As safety variables, we further investigate the levels of the applied antibiotics (usually ampicillin and sulbactam).
Detailed description
In December 2019, a series of unexplained cases of pneumonia in the city of Wuhan in China has come to light. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (first named 2019-nCoV, then SARS-CoV-2). The disease spread rapidly in the city of Wuhan in early 2020 and soon beyond. On 30 January 2020, the Director-General of the World Health Organization (WHO) declared the outbreak a public health emergency of international concern, and on 11 March 2020, the World Health Organization declared the virus a pandemic.
In humans, an infection with the virus can cause respiratory infections and even very severe pneumonia, which often ends fatally, especially in old and previously ill patients. Due to the novelty of the virus, the data basis for therapy is very limited. To date, there are no clinical data for an effective specific therapy, nor is there a vaccination against the virus available, so that therapy, especially intensive care treatment for very severe cases, must concentrate only on supportive treatment of lung failure and other complications.
The virus is very contagious and infection results in a relevant number of deaths. Due to very uncertain data on the spread of the virus in the population, it is difficult to estimate the mortality rate - case mortality is about 4% based on known case numbers.
In reports on the treatment of the first cases in Wuhan (Hubei Province, China) in January 2020, the need for intensive care treatment is described for about a quarter of the inpatient cases, 10-17% had to be ventilated invasively, and venous extracorporeal membrane oxygenation (vv-ECMO) was necessary in 2-4% of the inpatient cases. Patients requiring ECMO have an extremely high mortality rate of 83-100% in the studies described so far.
In severe cases a pronounced release of vasoactive cytokines was repeatedly observed. Excessive release of these vasoactive mediators ("cytokine storm") can result in pronounced vasodilatation and membrane leakage, which can ultimately lead to severe vasoplegic shock that is difficult to control. Ruan et al. and Zhou et al. have identified high interleukin 6 (IL-6) levels as a potential predictor of a fatal outcome when compared between survivors and patients who died of COVID-19 disease.
IL-6 is also an important factor in the pathophysiology of severe septic shock and excessive immune response in hemophagocytic lymphohistiocytosis (HLH) - for both indications has been shown, that the extracorporeal adsorption of IL-6 and other vasoactive substances in a CytoSorb® adsorber (CytoSorbents Corporation, Monmouth Junction, NJ, USA) leads to a significant reduction of these cytokines in the patient blood. Clinical experience and (previously unpublished) data from our monocentric registry study show that cytokine adsorption in a CytoSorb® Adsorber can also be safely integrated into a vv-ECMO system.
The aim of the study is to investigate the influence of extracorporeal cytokine adsorption on humoral inflammation parameters and patient survival under controlled conditions in patients with severe COVID-19 disease requiring extracorporeal membrane oxygenation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- randomized controlled trial examining COVID-patients requiring vv-ECMO therapy (+/- cytokine adsorption)
| Arm | Type | Receives |
|---|---|---|
| vv-ECMO + cytokine adsorption | Experimental | Device: vv-ECMO + cytokine adsorption (Cytosorb adsorber)after indication of treatment with vv-ECMO in acute respiratory failure in COVID-19-disease, patients will additionally receive cytokine adsorption using a Cytosorb adsorber |
| control-arm: vv-ECMO (no cytokine adsorption) | Other | Device: vv-ECMO only (no cytokine adsorption)treatment with vv-ECMO in acute respiratory failure in COVID-19-disease (standard treatment without additional cytokine adsorption) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- SARS-CoV-2-infection with COVID-pneumonia
- vv-ECMO therapy
Key exclusion criteria (1 listed)
- pregnancy, breastfeeding
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 |
|---|---|---|
| vv-ECMO + cytokine adsorption (Cytosorb adsorber)in COVID-19-diseased vv-ECMO patients additional treatment with cytokine adsorption using a Cytosorb adsorber will be randomized (vs. control group) | Device | vv-ECMO + cytokine adsorption |
| vv-ECMO only (no cytokine adsorption)COVID-19-diseased treated with vv-ECMO | Device | control-arm: vv-ECMO (no cytokine adsorption) |
Primary outcome
interleukin-6 (IL-6) level after 72 hours
Time frame: 72 hours
measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)
4 secondary outcomes
30-day-survival
Time frame: 72 hours
vasopressor dosage
Time frame: 72 hours
fluid balance
Time frame: 72 hours
lactate
Time frame: 72 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2021.
- Derived from this study: PubMed 34000236Supady A, Weber E, Rieder M, Lother A, Niklaus T, Zahn T, Frech F, Muller S, Kuhl M, Benk C, Maier S, Trummer G, Flugler A, Kruger K, Sekandarzad A, Stachon P, Zotzmann V, Bode C, Biever PM, Staudacher D, Wengenmayer T, Graf E, Duerschmied D. Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial. Lancet Respir Med. 2021 Jul;9(7):755-762. doi: 10.1016/S2213-2600(21)00177-6. Epub 2021 May 14.
- Individual participant dataSharing planned: No
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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.
Alexander Supady, Dr., MPH principal investigator
University Clinic Freiburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing vv-ECMO + cytokine adsorption (Cytosorb adsorber) and vv-ECMO only (no cytokine adsorption) in people with Coronavirus and COVID-19, run by Dr. Alexander Supady 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 2 inclusion and 1 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: finished, as of the sponsor's last update on 15 Mar 2021. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
interleukin-6 (IL-6) level after 72 hours (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 NCT04324528, which also lists 1 linked publication.
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 15 Mar 2021.