RescuE pLAsma eXchange in Severe COVID-19 (RELAX)

RescuE pLAsma eXchange in Severe COVID-19 (RELAX Severe COVID-19)

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 Overview

• Status: Terminated
• Conditions: Covid19; Therapeutic Plasma Exchange
• Intervention / Treatment: Other: Therapeutic plasma exchange

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Heidelberg University Hospital
    • Stuttgart, Baden-Württemberg, Germany, 70174
      • Klinikum Stuttgart
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45147
      • University Hospital Essen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: COVID-19 therapy according to center standard alone
Active Comparator: Therapeutic plasma exchange and COVID-19 therapy according to center standard	Other: Therapeutic plasma exchange; Treatment with therapeutic plasma exchange. Plasma from healthy donors is used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Intention to treat analysis	30 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Intention to treat & per protocol	15, 30, 60, 90, 365 days after randomization
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
Incidence of acute kidney injury, renal replacement therapy and renal recovery	AKI KDIGO criteria	15, 30, 60, 90 days after randomization
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

Collaborators and Investigators

• Sponsor: Heidelberg University

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2020
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: December 24, 2020
• First Posted (Actual): December 28, 2020

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Covid19; Plasma exchange
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: S-911/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: On request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No