Clinical trial NCT04898062: CRP-Apheresis for Attenuation of Pulmonary, MYocardial and/or Kidney Injury in COvid-19
Official title: Randomized, Controlled, Proof-Of-Concept Trial of CRP-Apheresis for Attenuation of Pulmonary MYocardial and/or Kidney Injury in COvid-19
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Covid19
Keywords: CRP-apheresis
COVID-19
SARS-CoV-2
Lead sponsor: Pentracor GmbH
Sponsor class: INDUSTRY
First posted: 2021-05-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The 'CAPMYKCO' study is a randomized controlled, open-label, single center proof of concept trial. The aim of this study is to evaluate whether a CRP-apheresis in addition to the current standard therapy is intended to mitigate the severity of the disease course of SARS-CoV-2, especially with regard to tissue injury in the lungs, heart and kidneys and their consequences.

CRP-apheresis should reduce the necessity and duration of non-invasive/invasive ventilation requirements compared to the control group.

The influence of CRP-apheresis on the attenuation of pulmonary, myocardial and/or kidney tissue injury as well as the course of the COVID-19 disease will also be demonstrated by evaluating various biomarkers, several clinical scoring systems, and the duration of intensive care medical treatment.

Detailed description: The prognostic value of C-reactive protein (CRP) in assessing disease progression in COVID-19 is well known: The steeper the CRP rise in the days after infection and the higher the CRP concentration at hospitalization, the worse the prognosis. It is believed that CRP concentration not only reflects tissue damage but also causally contributes to the severity of the damage that occurs. CRP apheresis effectively limits CRP rise, which may lead to improved prognosis. CRP apheresis is a therapeutic hemapheresis procedure that selectively removes C-reactive protein from the patient's plasma. Other causal therapies for immediate selective reduction of CRP in the acute phase of disease are not currently available.

In the planned 'CAPMYKCO' study, CRP-apheresis in addition to current standard COVID-19 therapy is expected to mitigate the severity of disease progression, particularly with regard to tissue injury in the lungs, the heart and/or the kidneys and their respective clinical consequences.

CRP-apheresis treatment in COVID-19 patients should reduce the necessity and duration of non-invasive / invasive ventilation compared to the control group.

The influence of CRP-apheresis on the course of the COVID-19 disease will also be demonstrated by evaluating different organ biomarkers and the duration of intensive medical treatment.

Eligibility criteria: Inclusion Criteria:

* Confirmed SARS CoV-2 infection (PCR-test)
* Oxygen therapy (maximum 'high-flow' therapy)
* CRP plasma concentration ≥ 50 mg/l and/or
* CRP increase ≥ 15 mg/l within 24 h after admission.
* Completed informed consent and written informed consent.
* Legal capacity

Exclusion Criteria:

* Age \< 18 years
* Pregnancy / lactation period
* Invasive, mechanical ventilation
* Extracorporeal membrane oxygenation (ECMO)
* Participation in other interventional trials
* Extracorporeal membrane oxygenation (ECMO) support
* Participation in other interventional trials

Primary outcomes:
measure: Necessity and duration of non-invasive/ invasive ventilation
timeFrame: through study completion, an average of 14 days
Secondary outcomes:
measure: Length of intensive care unit stay
timeFrame: through study completion, an average of 14 days
measure: Necessity of endotracheal intubation
timeFrame: through study completion, an average of 14 days
measure: Reduction of lung injury
timeFrame: through study completion, an average of 14 days
measure: Reduction of myocardial damage
timeFrame: up to 10 days
measure: Reduction of kidney damage
timeFrame: up to 10 days
measure: Improvement in general immune status
timeFrame: up to 10 days
measure: Cardiovascular, respiratory and renal SOFA score
timeFrame: through study completion, an average of 14 days
measure: Respiratory events
timeFrame: through study completion, an average of 14 days
measure: Myocardial events
timeFrame: through study completion, an average of 14 days
measure: Renal events
timeFrame: through study completion, an average of 14 days
measure: Safety of CRF apheresis
timeFrame: through study completion, an average of 14 days
Other outcomes:
Locations:
city: Essen
country: Germany
facility: West-German Heart and Vascular Center, University Duisburg-Essen
state: NRW
city: Berlin
country: Germany
facility: Gemeinschaftskrankenhaus Havelhöhe gGmbH
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Kempten
country: Germany
facility: Klinikverbund Allgäu gGmbH
Study officials:
affiliation: West-German Heart and Vascular Center, University Duisburg-Essen
name: Matthias Thielmann, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mueller AA, Tamura T, Crowley CP, DeGrado JR, Haider H, Jezmir JL, Keras G, Penn EH, Massaro AF, Kim EY. Inflammatory Biomarker Trends Predict Respiratory Decline in COVID-19 Patients. Cell Rep Med. 2020 Nov 17;1(8):100144. doi: 10.1016/j.xcrm.2020.100144. Epub 2020 Oct 29.
citation: Smilowitz NR, Kunichoff D, Garshick M, Shah B, Pillinger M, Hochman JS, Berger JS. C-reactive protein and clinical outcomes in patients with COVID-19. Eur Heart J. 2021 Jun 14;42(23):2270-2279. doi: 10.1093/eurheartj/ehaa1103.
citation: Kunze R. C-Reactive Protein: From Biomarker to Trigger of Cell Death? Ther Apher Dial. 2019 Dec;23(6):494-496. doi: 10.1111/1744-9987.12802. No abstract available.
citation: Torzewski J, Heigl F, Zimmermann O, Wagner F, Schumann C, Hettich R, Bock C, Kayser S, Sheriff A. First-in-Man: Case Report of Selective C-Reactive Protein Apheresis in a Patient with SARS-CoV-2 Infection. Am J Case Rep. 2020 Jul 14;21:e925020. doi: 10.12659/AJCR.925020.
citation: Pepys MB. C-reactive protein predicts outcome in COVID-19: is it also a therapeutic target? Eur Heart J. 2021 Jun 14;42(23):2280-2283. doi: 10.1093/eurheartj/ehab169. No abstract available.
citation: Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988 Sep;138(3):720-3. doi: 10.1164/ajrccm/138.3.720. No abstract available.
citation: Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996 Jul;22(7):707-10. doi: 10.1007/BF01709751. No abstract available.
citation: Ringel J, Ramlow A, Bock C, Sheriff A. Case Report: C-Reactive Protein Apheresis in a Patient With COVID-19 and Fulminant CRP Increase. Front Immunol. 2021 Aug 2;12:708101. doi: 10.3389/fimmu.2021.708101. eCollection 2021.
citation: Torzewski J, Zimmermann O, Kayser S, Heigl F, Wagner F, Sheriff A, Schumann C. Successful Treatment of a 39-Year-Old COVID-19 Patient with Respiratory Failure by Selective C-Reactive Protein Apheresis. Am J Case Rep. 2021 Aug 5;22:e932964. doi: 10.12659/AJCR.932964.
citation: Schumann C, Heigl F, Rohrbach IJ, Sheriff A, Wagner L, Wagner F, Torzewski J. A Report on the First 7 Sequential Patients Treated Within the C-Reactive Protein Apheresis in COVID (CACOV) Registry. Am J Case Rep. 2022 Jan 10;23:e935263. doi: 10.12659/AJCR.935263.