Clinical trial NCT04818866: International Study of Inflammation in COVID-19
Official title: The International Study of Inflammation in COVID-19: A Prospective Multi-Center Observational Study Examining the Role of Biomarkers of Inflammation in Predicting Covid-19 Related Outcomes in Hospitalized Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Covid19
Outcome, Fatal
Respiratory Failure
Acute Kidney Injury
Inflammation
Keywords: SuPAR
CRP
D-dimer
Ferritin
Interleukin-6
Procalcitonin
lactate dehydrogenase
biomarkers
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Rush University
name: Copenhagen University Hospital, Hvidovre
name: University of Athens
name: Heinrich-Heine University, Duesseldorf
name: University of Thessaly
name: Charite University, Berlin, Germany
First posted: 2021-03-26
Enrollment: 4463
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients hospitalized primarily for Covid-19

Brief summary: This is a prospective multi-center observational study which purpose is to evaluate the ability of blood-based inflammatory markers to risk-stratify patients hospitalized for Covid-19. Blood-based biomarkers examined include: soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein (CRP), procalcitonin, D-dimer, ferritin, lactate dehydrogenase and interleukin-6.

Detailed description: All consecutive patients hospitalized specifically for Covid-19 at the University of Michigan in Ann Arbor from February 1st, 2020 to date are included. Other participating centers will enroll patients depending on their variable capacity. Patients with a positive test for SARS-CoV-2 but hospitalized for non-Covid-19 reasons were excluded. Blood-based biomarkers including soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein (CRP), procalcitonin, D-dimer, ferritin, lactate dehydrogenase and interleukin-6 are measured in samples collected within 48 hours of presentation. The primary outcome of the study is the composite endpoint of in-hospital mortality, need for mechanical ventilation and need for renal replacement therapy.

Eligibility criteria: Inclusion Criteria:

* Positive SARS-CoV-2 test result
* Covid-19 as the primary reason for hospitalization

Exclusion Criteria:

* Hospitalized primarily for non-Covid-19 reasons

Primary outcomes:
measure: In-hospital incidence of death, need for mechanical ventilation and need for renal replacement therapy
timeFrame: during COVID91 related hospitalization, up to 6 months
Secondary outcomes:
measure: Length of Hospitalization
timeFrame: up to 6 months
measure: Acute Kidney Injury
timeFrame: within 6 months
measure: Cardiovascular Events
timeFrame: within 6 months
measure: Death
timeFrame: within 6 months
measure: Need for renal replacement therapy
timeFrame: within 6 months
measure: Need for mechanical ventilation
timeFrame: within 6 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Salim S Hayek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rovina N, Akinosoglou K, Eugen-Olsen J, Hayek S, Reiser J, Giamarellos-Bourboulis EJ. Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia. Crit Care. 2020 Apr 30;24(1):187. doi: 10.1186/s13054-020-02897-4. No abstract available.
citation: Azam TU, Berlin H, Anderson E, Pan M, Shadid HR, Padalia K, O'Hayer P, Meloche C, Feroze R, Michaud E, Launius C, Blakely P, Bitar A, Willer C, Pop-Busui R, Carethers JM, Hayek SS. Differences in Inflammation, Treatment, and Outcomes Between Black and Non-Black Patients Hospitalized for COVID-19: A Prospective Cohort Study. Am J Med. 2022 Mar;135(3):360-368. doi: 10.1016/j.amjmed.2021.10.026. Epub 2021 Nov 16.
citation: Vasbinder A, Anderson E, Shadid H, Berlin H, Pan M, Azam TU, Khaleel I, Padalia K, Meloche C, O'Hayer P, Michaud E, Catalan T, Feroze R, Blakely P, Launius C, Huang Y, Zhao L, Ang L, Mikhael M, Mizokami-Stout K, Pennathur S, Kretzler M, Loosen SH, Chalkias A, Tacke F, Giamarellos-Bourboulis EJ, Reiser J, Eugen-Olsen J, Feldman EL, Pop-Busui R, Hayek SS; ISIC Study Group. Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19. Diabetes Care. 2022 Mar 1;45(3):692-700. doi: 10.2337/dc21-2102.
citation: Pan M, Vasbinder A, Anderson E, Catalan T, Shadid HR, Berlin H, Padalia K, O'Hayer P, Meloche C, Azam TU, Khaleel I, Michaud E, Blakely P, Bitar A, Huang Y, Zhao L, Pop-Busui R, Loosen SH, Chalkias A, Tacke F, Giamarellos-Bourboulis EJ, Reiser J, Eugen-Olsen J, Hayek SS; ISIC Group. Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID-19. J Am Heart Assoc. 2021 Dec 21;10(24):e023535. doi: 10.1161/JAHA.121.023535. Epub 2021 Dec 10.
citation: Azam TU, Shadid HR, Blakely P, O'Hayer P, Berlin H, Pan M, Zhao P, Zhao L, Pennathur S, Pop-Busui R, Altintas I, Tingleff J, Stauning MA, Andersen O, Adami ME, Solomonidi N, Tsilika M, Tober-Lau P, Arnaoutoglou E, Keitel V, Tacke F, Chalkias A, Loosen SH, Giamarellos-Bourboulis EJ, Eugen-Olsen J, Reiser J, Hayek SS; International Study of Inflammation in COVID-19. Soluble Urokinase Receptor (SuPAR) in COVID-19-Related AKI. J Am Soc Nephrol. 2020 Nov;31(11):2725-2735. doi: 10.1681/ASN.2020060829. Epub 2020 Sep 22.
citation: Hayek SS, Roderburg C, Blakely P, Launius C, Eugen-Olsen J, Tacke F, Ktena S, Keitel V, Luedde M, Giamarellos-Bourboulis EJ, Luedde T, Loosen SH. Circulating Osteopontin Levels and Outcomes in Patients Hospitalized for COVID-19. J Clin Med. 2021 Aug 30;10(17):3907. doi: 10.3390/jcm10173907.
citation: Vasbinder A, Meloche C, Azam TU, Anderson E, Catalan T, Shadid H, Berlin H, Pan M, O'Hayer P, Padalia K, Blakely P, Khaleel I, Michaud E, Huang Y, Zhao L, Pop-Busui R, Gupta S, Eagle K, Leaf DE, Hayek SS; STOP-COVID Investigatorsdouble dagger. Relationship Between Preexisting Cardiovascular Disease and Death and Cardiovascular Outcomes in Critically Ill Patients With COVID-19. Circ Cardiovasc Qual Outcomes. 2022 Oct;15(10):e008942. doi: 10.1161/CIRCOUTCOMES.122.008942. Epub 2022 Oct 4.
citation: Luo S, Vasbinder A, Du-Fay-de-Lavallaz JM, Gomez JMD, Suboc T, Anderson E, Tekumulla A, Shadid H, Berlin H, Pan M, Azam TU, Khaleel I, Padalia K, Meloche C, O'Hayer P, Catalan T, Blakely P, Launius C, Amadi KM, Pop-Busui R, Loosen SH, Chalkias A, Tacke F, Giamarellos-Bourboulis EJ, Altintas I, Eugen-Olsen J, Williams KA, Volgman AS, Reiser J, Hayek SS; ISIC (International Study of Inflammation in COVID-19) Group. Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID-19. J Am Heart Assoc. 2022 Sep 20;11(18):e025198. doi: 10.1161/JAHA.122.025198. Epub 2022 Aug 4.
citation: Zhu K, Mukherjee K, Wei C, Hayek SS, Collins A, Gu C, Corapi K, Altintas MM, Wang Y, Waikar SS, Bianco AC, Koch A, Tacke F, Reiser J, Sever S. The D2D3 form of uPAR acts as an immunotoxin and may cause diabetes and kidney disease. Sci Transl Med. 2023 Sep 20;15(714):eabq6492. doi: 10.1126/scitranslmed.abq6492. Epub 2023 Sep 20.