The spectrum of coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to acute respiratory distress syndrome ("ARDS") and patient death. Severely affected patients may develop a cytokine storm-like clinical syndrome with high mortality. Laboratory tests in these patients show an excessive and uncontrolled immune response with consecutive multi-organ failure. In addition, there is evidence for the development of prothrombotic autoantibodies as an epiphenomenon of "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2) infection. Therapeutic plasma exchange ("TPE") is being discussed as a therapeutic alternative in patients with severe, refractory COVID-19. The idea is that plasma exchange eliminates both endogenous and exogenous inducers of an exuberant inflammatory response as well as prothrombotic factors, thus breaking the secondary vicious circle of SARS-CoV-2 infection. In general, TPE is a safe procedure with known efficacy in other severe viral diseases as well as in cytokine storm-like diseases and ARDS of other geneses. Moreover, initial data, mostly derived from case studies, demonstrate promising therapeutic efficacy of TPE in severe COVID-19 courses with previously lacking treatment options. To further evaluate the therapeutic efficacy of TPE in severe COVID-19, a prospective randomized controlled trial of TPE in severe SARS-CoV-2 infection is being conducted at our center. Patients will be randomized to a control group (standard therapy according to center standards) and a therapy/intervention group (standard therapy + TPE).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
67
Treatment with therapeutic plasma exchange. Plasma from healthy donors is used.
Heidelberg University Hospital
Heidelberg, Baden-Wurttemberg, Germany
Klinikum Stuttgart
Stuttgart, Baden-Wurttemberg, Germany
University Hospital Essen
Essen, North Rhine-Westphalia, Germany
Survival
Intention to treat analysis
Time frame: 30 days after randomization
Survival
Intention to treat \& per protocol
Time frame: 15, 30, 60, 90, 365 days after randomization
Ventilator-free days
Time frame: 15, 30, 60, 90 days after randomization
Length of hospital an ICU stay
Time frame: through study completion, an average of 1 year
Improvement defined as two points on seven point ordinal WHO scale
Time frame: through study completion, an average of 1 year
Reduction of vasopressors after TPE treatments
Time frame: through study completion, an average of 1 year
Incidence of acute kidney injury, renal replacement therapy and renal recovery
AKI KDIGO criteria
Time frame: 15, 30, 60, 90 days after randomization
Frequency of typical complications associated to therapeutic plasma exchange
Time frame: through study completion, an average of 1 year
Reduction of inflammation mediators, (auto-)antibodies, and coagulation-associated molecules and their temporal correlation to TPE
Time frame: through study completion, an average of 1 year
D-dimer-dependent assessment of therapeutic efficacy.
Time frame: through study completion, an average of 1 year
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