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RescuE pLAsma eXchange in Severe COVID-19

Not Applicable
Terminated
Conditions
Therapeutic Plasma Exchange
Covid19
Interventions
Other: Therapeutic plasma exchange
Registration Number
NCT04685655
Lead Sponsor
Heidelberg University
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
67
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Therapeutic plasma exchange and COVID-19 therapy according to center standardTherapeutic plasma exchange-
Primary Outcome Measures
NameTimeMethod
Survival30 days after randomization

Intention to treat analysis

Secondary Outcome Measures
NameTimeMethod
Ventilator-free days15, 30, 60, 90 days after randomization
Frequency of typical complications associated to therapeutic plasma exchangethrough study completion, an average of 1 year
Survival15, 30, 60, 90, 365 days after randomization

Intention to treat \& per protocol

Length of hospital an ICU staythrough study completion, an average of 1 year
Improvement defined as two points on seven point ordinal WHO scalethrough study completion, an average of 1 year
Reduction of vasopressors after TPE treatmentsthrough study completion, an average of 1 year
Incidence of acute kidney injury, renal replacement therapy and renal recovery15, 30, 60, 90 days after randomization

AKI KDIGO criteria

Reduction of inflammation mediators, (auto-)antibodies, and coagulation-associated molecules and their temporal correlation to TPEthrough study completion, an average of 1 year
D-dimer-dependent assessment of therapeutic efficacy.through study completion, an average of 1 year

Trial Locations

Locations (3)

Klinikum Stuttgart

🇩🇪

Stuttgart, Baden-Württemberg, Germany

University Hospital Essen

🇩🇪

Essen, Nordrhein-Westfalen, Germany

Heidelberg University Hospital

🇩🇪

Heidelberg, Baden-Württemberg, Germany

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