RELAX: RescuE pLAsma eXchange in Severe COVID-19

• Sponsor: Heidelberg University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04685655
• Collaborator: (none)
• Enrollment: 228
• Locations: 3
• Arms: 2
• Anticipated Duration (Months): 35.8
• Patients Per Site: 76
• Patients Per Site Per Month: 2.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Therapeutic Plasma Exchange; Covid19	Other: Therapeutic plasma exchange	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 228 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Therapeutic plasma exchange in patients with severe COVID 19Therapeutic plasma exchange in patients with severe COVID 19
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: RescuE pLAsma eXchange in Severe COVID-19 (RELAX Severe COVID-19)
• Actual Study Start Date: Jan 7, 2020
• Anticipated Primary Completion Date: May 31, 2022
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Survival [30 days after randomization]

   Intention to treat analysis

Secondary Outcome Measures

1. Survival [15, 30, 60, 90, 365 days after randomization]

   Intention to treat & per protocol

2. Ventilator-free days [15, 30, 60, 90 days after randomization]

3. Length of hospital an ICU stay [through study completion, an average of 1 year]

4. Improvement defined as two points on seven point ordinal WHO scale [through study completion, an average of 1 year]

5. Reduction of vasopressors after TPE treatments [through study completion, an average of 1 year]

6. Incidence of acute kidney injury, renal replacement therapy and renal recovery [15, 30, 60, 90 days after randomization]

   AKI KDIGO criteria

7. Frequency of typical complications associated to therapeutic plasma exchange [through study completion, an average of 1 year]

8. Reduction of inflammation mediators, (auto-)antibodies, and coagulation-associated molecules and their temporal correlation to TPE [through study completion, an average of 1 year]

9. D-dimer-dependent assessment of therapeutic efficacy. [through study completion, an average of 1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Heidelberg University Hospital	Heidelberg	Baden-Württemberg	Germany	69120
2	Klinikum Stuttgart	Stuttgart	Baden-Württemberg	Germany	70174
3	University Hospital Essen	Essen	Nordrhein-Westfalen	Germany	45147

Sponsors and Collaborators

• Heidelberg University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Christian Nusshag, MD, Attending, Department of Nephrology, University Hospital Heidelberg
• ClinicalTrials.gov Identifier: NCT04685655
• Other Study ID Numbers: S-911/2020
• First Posted: Dec 28, 2020
• Last Update Posted: Mar 15, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Christian Nusshag, MD, Attending, Department of Nephrology, University Hospital Heidelberg: Plasma exchange; Covid19
• Additional relevant MeSH terms: COVID-19

Study Results

No Results Posted as of Mar 15, 2022