Clinical trial NCT04685655: RescuE pLAsma eXchange in Severe COVID-19
Official title: RescuE pLAsma eXchange in Severe COVID-19 (RELAX Severe COVID-19)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Therapeutic Plasma Exchange
Covid19
Keywords: Plasma exchange
Covid19
Lead sponsor: Heidelberg University
Sponsor class: OTHER
First posted: 2020-12-28
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Therapeutic plasma exchange in patients with severe COVID 19
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Survival
timeFrame: 30 days after randomization
Secondary outcomes:
measure: Survival
timeFrame: 15, 30, 60, 90, 365 days after randomization
measure: Ventilator-free days
timeFrame: 15, 30, 60, 90 days after randomization
measure: Length of hospital an ICU stay
timeFrame: through study completion, an average of 1 year
measure: Improvement defined as two points on seven point ordinal WHO scale
timeFrame: through study completion, an average of 1 year
measure: Reduction of vasopressors after TPE treatments
timeFrame: through study completion, an average of 1 year
measure: Incidence of acute kidney injury, renal replacement therapy and renal recovery
timeFrame: 15, 30, 60, 90 days after randomization
measure: Frequency of typical complications associated to therapeutic plasma exchange
timeFrame: through study completion, an average of 1 year
measure: Reduction of inflammation mediators, (auto-)antibodies, and coagulation-associated molecules and their temporal correlation to TPE
timeFrame: through study completion, an average of 1 year
measure: D-dimer-dependent assessment of therapeutic efficacy.
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Heidelberg University Hospital
state: Baden-Württemberg
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
state: Baden-Württemberg
city: Essen
country: Germany
facility: University Hospital Essen
state: Nordrhein-Westfalen
Study officials:
References: