Covid19, Therapeutic Plasma Exchange
Conditions
Keywords
Plasma exchange, Covid19
Brief summary
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).
Interventions
Treatment with therapeutic plasma exchange. Plasma from healthy donors is used.
Sponsors
Heidelberg University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Therapeutic plasma exchange in patients with severe COVID 19
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent by the study participant or their legally appointed representative. * Age ≥ 18 years * Evidence of acute SARS-CoV-2 infection, confirmed by PCR testing * Invasive ventilation * Fever ≥ 38.5°C, confirmed by a total of 3 consecutive measurements or ongoing renal replacement therapy and temperature ≥ 37.5°C * D-dimers ≥ 2mg/L * Dexamethasone ≥ 6mg/day or equivalent dose on at least 2 days
Exclusion criteria
* Age \> 85 years * Pre-existing treatment limitations * Pregnancy * Confirmed pulmonary arterial embolism with hemodynamically relevant right heart strain * ST-segment elevation myocardial infarction (STEMI) * Participation in an intervention study elsewhere
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | 30 days after randomization | Intention to treat analysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator-free days | 15, 30, 60, 90 days after randomization | — |
| Length of hospital an ICU stay | through study completion, an average of 1 year | — |
| Improvement defined as two points on seven point ordinal WHO scale | through study completion, an average of 1 year | — |
| Reduction of vasopressors after TPE treatments | through study completion, an average of 1 year | — |
| Survival | 15, 30, 60, 90, 365 days after randomization | Intention to treat & per protocol |
| Frequency of typical complications associated to therapeutic plasma exchange | through study completion, an average of 1 year | — |
| Reduction of inflammation mediators, (auto-)antibodies, and coagulation-associated molecules and their temporal correlation to TPE | through study completion, an average of 1 year | — |
| D-dimer-dependent assessment of therapeutic efficacy. | through study completion, an average of 1 year | — |
| Incidence of acute kidney injury, renal replacement therapy and renal recovery | 15, 30, 60, 90 days after randomization | AKI KDIGO criteria |
Countries
Germany
Outcome results
None listed