Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04324528 |
| Other study ID # |
CYCOV |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 27, 2020 |
| Est. completion date |
January 27, 2021 |
Study information
| Verified date |
March 2021 |
| Source |
University Hospital Freiburg |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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). 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).
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.
