CRP-Apheresis for Attenuation of Pulmonary, MYocardial and/or Kidney Injury in COvid-19

Covid19 Clinical Trial

— CAPMYKCO  

Official title:

Randomized, Controlled, Proof-Of-Concept Trial of CRP-Apheresis for Attenuation of Pulmonary MYocardial and/or Kidney Injury in COvid-19

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04898062
• Other study ID #: 21-10018-BO
• Status: Withdrawn
• Phase: N/A
• Start date: May 5, 2021
• Est. completion date: March 31, 2023

Study information

• Verified date: September 2022
• Source: Pentracor GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Device:
• CRP-apheresis
The major advantages of depleting C-reactive protein by therapeutic apheresis are the selective removal of the damaging agent by the highly specific ligand and the good controllability of the procedure, since the plasma can be passed over the column as often as necessary to achieve the desired reduction. In addition, treatment can be interrupted or discontinued at any time.

Locations

Country	Name	City	State
Germany	Gemeinschaftskrankenhaus Havelhöhe gGmbH	Berlin
Germany	West-German Heart and Vascular Center, University Duisburg-Essen	Essen	NRW
Germany	Universitätsklinikum des Saarlandes	Homburg
Germany	Klinikverbund Allgäu gGmbH	Kempten

Sponsors (1)

Lead Sponsor	Collaborator
Pentracor GmbH

Country where clinical trial is conducted

Germany, 

References & Publications (10)

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. — View 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. — View 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. Erratum In: Am Rev Respir Dis 1989 Apr;139(4):1065. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Necessity and duration of non-invasive/ invasive ventilation	In the intervention group, a reduced necessity and duration of non-invasive/ invasive ventilation is expected.	through study completion, an average of 14 days
Secondary	Length of intensive care unit stay	In the intervention group, a shorter intensive care unit stay is expected.	through study completion, an average of 14 days
Secondary	Necessity of endotracheal intubation	In the intervention group, a reduced necessity of endotracheal intubation is expected.	through study completion, an average of 14 days
Secondary	Reduction of lung injury	In the intervention group, a reduced lung injury as reflected by peripheral oxygen saturation, oxygen supplementation, Horovitz index, lung injury score is expected.	through study completion, an average of 14 days
Secondary	Reduction of myocardial damage	In the intervention group, a reduced myocardial damage as reflected by hs troponin, creatin kinase, creatin kinase MB fraction is expected.	up to 10 days
Secondary	Reduction of kidney damage	In the intervention group, a reduced kidney damage as reflected by creatinine, glomerular filtration rate, onset of dialysis, CKD stadium is expected.	up to 10 days
Secondary	Improvement in general immune status	In the intervention group, an improved general immune status as reflected by CRP, fibrinogen, leukocytes, thrombocytes and lactate dehydrogenase is expected.	up to 10 days
Secondary	Cardiovascular, respiratory and renal SOFA score	In the intervention group, improvements in cardiovascular, respiratory and renal SOFA scores are expected.; *(Vincent JL: 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. In:Intensive Care Med 1996:22;707-10.)	through study completion, an average of 14 days
Secondary	Respiratory events	In the intervention group, a reduction of respiratory events (pulmonary embolism) is expected.	through study completion, an average of 14 days
Secondary	Myocardial events	In the intervention group, a reduction of cardial events (cardiac arrhythmias, myocardial infarction, cardiopulmonary resuscitation, low cardiac output syndrome (LCOS), operation, percutaneous coronary intervention (PCI), angina pectoris) is expected.	through study completion, an average of 14 days
Secondary	Renal events	In the intervention group, a reduction of renal events (onset of dialysis requirement, deterioration of renal function (CKD increase) is expected.	through study completion, an average of 14 days
Secondary	Safety of CRF apheresis	In the intervention group, the absence of serious incidents is expected.	through study completion, an average of 14 days