An interventional study of vv-ECMO + cytokine adsorption (Cytosorb adsorber) and vv-ECMO only (no cytokine adsorption) in Coronavirus Infection, COVID and SARS-CoV 2, sponsored by Dr. Alexander Supady. Suspended at 3 sites in Germany. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2021-03-15.
Sponsored by Dr. Alexander Supady · Not applicable, Interventional, and Treatment
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.
The aim of the study is to investigate the influence of extracorporeal cytokine adsorption on interleukin-6-levels and time to successful ECMO explantation under controlled conditions in patients with particularly severe COVID-19 disease requiring extracorporeal membrane oxygenation.
In December 2019, a series of unexplained cases of pneumonia in the city of Wuhan in China has come to light. In virologic 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 tract infections or even very severe pneumonia - these often end fatally, especially in old and pre-diseased 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 courses, must concentrate only on supportive treatment of lung failure and other complications.
The virus is highly 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 - the case fatality rate is about 4% based on the 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 veno-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 published, 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 severe vasodilatation and membrane leakage, which can ultimately lead to 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.
7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's planned enrollment of 80 is below the median of 100 across 4,099 interventional studies indexed under COVID-19.
Browse COVID-19 studies →Dr. Alexander Supady is the lead sponsor of 4 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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
Device: vv-ECMO + cytokine adsorption (Cytosorb adsorber)
treatment with vv-ECMO in acute respiratory failure in COVID-19-disease (standard treatment without additional cytokine adsorption)
Device: vv-ECMO only (no cytokine adsorption)
in COVID-19-diseased vv-ECMO patients additional treatment with cytokine adsorption using a Cytosorb adsorber will be randomized (vs. control group)
COVID-19-diseased treated with vv-ECMO
IL-6 reduction by 75% or more after 72 hours as compared to the baseline measurement
measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)
Time frame: 72 hours
time to successful ECMO-explantation
time to successful ECMO-explantation within 30 days after randomization
Time frame: 30 days
Ventilator free days (VFD)
Ventilator free days (VFD) in the first 30 days after randomization, where invasive mechanical ventilation (IMV), non-invasive ventilation (NIV) and ECMO are defined as ventilator days. VFD=0, if the patient dies in the first 30 days after randomization
Time frame: 30 days
Time to extubation from ventilation and explantation from ECMO
Time to extubation from ventilation and explantation from ECMO. Death under ventilation and/or ECMO will be analyzed as a competing event. The time will be censored at the time of last visit for surviving patients under ventilation and/or ECMO.
Time frame: 30 days
Overall survival time
Overall survival time, defined as time from randomization to death. The time will be censored at the time of last visit for surviving patients.
Time frame: 30 days
Days on intensive care unit (ICU)
Days on intensive care unit (ICU)
Time frame: 30 days
Vasopressor dosage
Vasopressor dosage of adrenaline, noradrenaline, vasopressin, and dobutamine at 24, 48,72 h
Time frame: 24, 48, 72 hours
Fluid substitution and fluid balance
Total fluid\[ml\] substitution and fluid balance \[ml\] at 24, 48, 72 h
Time frame: 24, 48, 72 hours
Serum lactate
Serum lactate at 24, 48, 72 h
Time frame: 24, 48, 72 hours
Urine output
Urine output at 24, 48, 72 h
Time frame: 24, 48, 72 hours
Willebrand factor
Willebrand factor at 24, 48, 72 h
Time frame: 24, 48, 72 hours
d-dimers
d-dimers at 24, 48, 72 h
Time frame: 24, 48, 72 hours
interleukin-6 levels
interleukin-6 levels at 24, 48, 72 h
Time frame: 24, 48, 72 hours
SOFA-Score
Sequential Organ Failure Assessment Score at 24, 48, 72 h (values from 6 to 24, where the higher values explain higher disease severity)
Time frame: 24, 48, 72 hours
serious adverse device effects
serious complications or malfunctions related to the CytoSorb device
Time frame: 30 days
adverse event of special interest: air in the ECMO system
unintended air in the ECMO system during operation of the device
Time frame: 30 days
adverse event of special interest: blood-clotting in the ECMO system
unintended blood-clotting in the ECMO system during operation of the device
Time frame: 30 days
adverse event of special interest: bleeding complications
major bleeding events
Time frame: 30 days
Plan to share: No
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Dr. Alexander Supady