Clinical Phenotypes in Pericarditis: IL-1RA Antibodies and suPAR Levels

NCT05925790 | Recruiting

• 1 other identifier: 2023/ST/094
• Study Type: observational
• Target: 146
• Locations: 2 countries
• Sites: 9

Brief Summary

This study aims to investigate the pathophysiology of recurrent pericarditis (RP) by testing for neutralizing autoantibodies against interleukin-1 receptor antagonist (IL-1RA) and measuring soluble urokinase plasminogen activator receptor (suPAR) levels. The hypothesis is that these tests will provide insights into both the inflammatory and non-inflammatory phenotypes of RP, shedding light on the underlying mechanisms. The study will assess the correlation between antibody levels, suPAR levels, and markers of cardiac damage and inflammation. Longitudinal testing during acute episodes and intercritical phases is also planned. The results may guide the use of anakinra, an IL-1 receptor antagonist, in specific clinical scenarios and optimize treatment strategies for RP.

Conditions

Pericarditis

Keywords

Pericarditis; Anti-interleukin-1 receptor antagonist antibodies; Soluble urokinase plasminogen activator receptor; Pericarditis phenotypes

Outcome Measures

Primary Outcomes (2)

• Assessment of IL-1RA antibodies across pericarditis phenotypes

  * Levels of anti-IL-1RA antibodies in different phenotypes of pericarditis. * Levels of anti-IL-1RA antibodies during acute episodes and intercritical phases.

  24 months

• Assessment of suPAR levels across pericarditis phenotypes

  * Levels of suPAR in acute and recurrent pericarditis with normal C-reactive protein (CRP). * Levels of suPAR during acute episodes and intercritical phases.

  24 months

Secondary Outcomes (2)

• Correlation of Time to Recurrence and Disease Activity with Anti-IL-1RA Antibodies in Pericarditis

  24 months

• Correlation of Time to Recurrence and Disease Activity with suPAR Levels in Pericarditis

  24 months

Study Arms (2)

Inflammatory phenotype

Patients with the inflammatory phenotype of recurrent pericarditis exhibit signs indicating the presence of an inflammatory process during a recurrence. These signs may include one or more of the following: * Fever * Elevated C-reactive protein (CRP) * Elevated white blood cell (WBC) count * Elevated erythrocyte sedimentation rate (ESR) * Pericardial late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) * Pericardial contrast enhancement on computed tomography (CT)

Diagnostic Test: IL1RA Antibody Assay; Diagnostic Test: suPAR Testing

Non-inflammatory phenotype

Patients with the non-inflammatory phenotype of recurrent pericarditis do not exhibit any of the signs typically associated with an active inflammatory process during a recurrence. These patients present without: * Fever * Elevated CRP * Elevated WBC count * Elevated ESR * Pericardial LGE on CMR * Pericardial contrast enhancement on CT

Diagnostic Test: IL1RA Antibody Assay; Diagnostic Test: suPAR Testing

Interventions

IL1RA Antibody Assay DIAGNOSTIC_TEST

-The measurement of anti-interleukin-1 receptor antagonist (IL1RA) antibodies will be performed using the ELISA (Enzyme-Linked Immunosorbent Assay) method,as previously described \[Thurner, L., et al., IL-1RA Antibodies in Myocarditis after SARS-CoV-2 Vaccination. N Engl J Med, 2022. 387(16): p. 1524-1527\].

Inflammatory phenotype; Non-inflammatory phenotype

suPAR Testing DIAGNOSTIC_TEST

-The quantitative determination of soluble urokinase plasminogen activator receptor (suPAR) levels in blood will be conducted using the commercially available "CHORUS suPAR Extended" kit (cod. 81414, DIESSE Diagnostica Senese S.p.A., Siena, Italy), based on the principle of the sandwich ELISA method.

Inflammatory phenotype; Non-inflammatory phenotype

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients with different phenotypes of pericarditis

You may qualify if:

• Written informed consent from patients aged ≥ 18 years before any evaluation is performed.
• Written informed consent from parents or legal guardian and assent from minors aged under 18 years before any evaluation is performed.
• Recurrent acute pericarditis during the acute phase of the disease. The diagnosis of pericarditis is based on the presence of at least two of the following criteria: typical pericarditic chest pain (acute and pleuritic, worsened by positional changes or breathing), pericardial friction rub, diffuse ST segment elevation or PR depressions not previously reported, and pericardial effusion.
• Post-cardiac injury pericarditis (e.g., post-cardiac surgery) that is new or worsening. Recurrence is diagnosed based on the same criteria.
• In all patients, the previous history of CRP values should be known to distinguish individuals with inflammatory forms (characterized by significantly elevated CRP values in the clinical history) from those with pericarditis and normal or near-normal CRP levels (clinical history of normal or at most less than 2 times the normal value).
• The acute phase of the disease is defined as follows: for pericarditis forms with elevated CRP, the presence of a CRP that is at least double the normal value of the test. For forms with normal CRP, it is based on clinical judgment, as there are no other recognized and validated criteria.

You may not qualify if:

• Specific etiologies, including tuberculosis, neoplastic or purulent etiologies, post-cardiac injury syndromes, and autoimmune rheumatic diseases.
• Subjects under 18 years of age.
• Pregnant or lactating women.
• History of immunosuppression, including a positive result on HIV screening tests (ELISA and Western blot).
• Positive QuantiFERON test (QFT-Tuberculosis G In-Tube) or positive Purified Protein Derivative (PPD) test after the initial clinical evaluation.
• History of other significant medical conditions that, according to the investigator, could compromise the outcome or interpretation of the results (e.g., systemic diseases that are not directly the cause of pericarditis but may cause a state of chronic inflammation).
• Use of any medication that the investigator believes could alter the result of the tests to be performed (except those used for the treatment of pericarditis).
• Throughout the study, patients will continue to receive the most appropriate therapies for their clinical condition, following current guidelines and good clinical practice, without the participation in the study prejudicing or influencing the choice of therapeutic strategies to be employed.

Sponsors & Collaborators

• ASST Fatebenefratelli Sacco: lead
• Fatebenefratelli Hospital: collaborator
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator
• Ospedale Galeazzi Sant'Ambrogio - IRCCS: collaborator
• Careggi Hospital: collaborator
• Azienda Ospedaliero Universitaria, Santa Maria della Misericordia di Udine, Italy: collaborator
• Children's Medical Hospital, University of Muenster, Muenster, Germany: collaborator
• University of Homburg: collaborator
• University Hospital Tuebingen: collaborator

Study Sites (9)

Saarland University

Homburg, Germany

RECRUITING

University Children's Hospital Muenster

Münster, Germany

NOT YET RECRUITING

University Hospital Tübingen

Tübingen, Germany

NOT YET RECRUITING

A.O.U. Careggi

Florence, Italy

NOT YET RECRUITING

Luigi Sacco Hospital - ASST Fatebenefratelli Sacco

Milan, 20157, Italy

RECRUITING

Fatebenefratelli Hospital - ASST Fatebenefratelli Sacco

Milan, Italy

RECRUITING

Ospedale Galeazzi Sant'Ambrogio - IRCCS, Poliambulatorio Cardiovascolare Cardiologia Universitaria

Milan, Italy

NOT YET RECRUITING

Policlinico di Milano Ospedale Maggiore, Fondazione IRCCS Ca' Granda

Milan, Italy

NOT YET RECRUITING

Ospedale Santa Maria della Misericordia dell'ASU-FC

Udine, Italy

NOT YET RECRUITING

Related Publications (12)

• Thurner L, Kessel C, Fadle N, Regitz E, Seidel F, Kindermann I, Lohse S, Kos I, Tschope C, Kheiroddin P, Kiblboeck D, Hoffmann MC, Bette B, Carbon G, Cetin O, Preuss KD, Christofyllakis K, Bittenbring JT, Pickardt T, Fischer Y, Thiele H, Baldus S, Stangl K, Steiner S, Gietzen F, Kerber S, Deneke T, Jellinghaus S, Linke A, Ibrahim K, Grabmaier U, Massberg S, Thilo C, Greulich S, Gawaz M, Mayatepek E, Meyer-Dobkowitz L, Kindermann M, Birk E, Birk M, Lainscak M, Foell D, Lepper PM, Bals R, Krawczyk M, Mevorach D, Hasin T, Keren A, Kabesch M, Abdul-Khaliq H, Smola S, Bewarder M, Thurner B, Bohm M, Pfeifer J, Klingel K. IL-1RA Antibodies in Myocarditis after SARS-CoV-2 Vaccination. N Engl J Med. 2022 Oct 20;387(16):1524-1527. doi: 10.1056/NEJMc2205667. Epub 2022 Sep 21. No abstract available.

  PMID: 36130012 BACKGROUND

• Chiabrando JG, Bonaventura A, Vecchie A, Wohlford GF, Mauro AG, Jordan JH, Grizzard JD, Montecucco F, Berrocal DH, Brucato A, Imazio M, Abbate A. Management of Acute and Recurrent Pericarditis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Jan 7;75(1):76-92. doi: 10.1016/j.jacc.2019.11.021.

  PMID: 31918837 BACKGROUND

• Lopalco G, Rigante D, Cantarini L, Imazio M, Lopalco A, Emmi G, Venerito V, Fornaro M, Frediani B, Nivuori M, Brucato A, Iannone F. The autoinflammatory side of recurrent pericarditis: Enlightening the pathogenesis for a more rational treatment. Trends Cardiovasc Med. 2021 Jul;31(5):265-274. doi: 10.1016/j.tcm.2020.04.006. Epub 2020 May 3.

  PMID: 32376492 BACKGROUND

• Mauro AG, Bonaventura A, Vecchie A, Mezzaroma E, Carbone S, Narayan P, Potere N, Cannata A, Paolini JF, Bussani R, Montecucco F, Sinagra G, Van Tassel BW, Abbate A, Toldo S. The Role of NLRP3 Inflammasome in Pericarditis: Potential for Therapeutic Approaches. JACC Basic Transl Sci. 2021 Feb 22;6(2):137-150. doi: 10.1016/j.jacbts.2020.11.016. eCollection 2021 Feb.

  PMID: 33665514 BACKGROUND

• Adler Y, Charron P, Imazio M, Badano L, Baron-Esquivias G, Bogaert J, Brucato A, Gueret P, Klingel K, Lionis C, Maisch B, Mayosi B, Pavie A, Ristic AD, Sabate Tenas M, Seferovic P, Swedberg K, Tomkowski W; ESC Scientific Document Group. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2015 Nov 7;36(42):2921-2964. doi: 10.1093/eurheartj/ehv318. Epub 2015 Aug 29. No abstract available.

  PMID: 26320112 BACKGROUND

• Klein A, Cremer P, Kontzias A, Furqan M, Tubman R, Roy M, Lim-Watson MZ, Magestro M. US Database Study of Clinical Burden and Unmet Need in Recurrent Pericarditis. J Am Heart Assoc. 2021 Aug 3;10(15):e018950. doi: 10.1161/JAHA.120.018950. Epub 2021 Jul 21.

  PMID: 34284595 BACKGROUND

• Brucato A, Imazio M, Gattorno M, Lazaros G, Maestroni S, Carraro M, Finetti M, Cumetti D, Carobbio A, Ruperto N, Marcolongo R, Lorini M, Rimini A, Valenti A, Erre GL, Sormani MP, Belli R, Gaita F, Martini A. Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial. JAMA. 2016 Nov 8;316(18):1906-1912. doi: 10.1001/jama.2016.15826.

  PMID: 27825009 BACKGROUND

• Imazio M, Andreis A, De Ferrari GM, Cremer PC, Mardigyan V, Maestroni S, Luis SA, Lopalco G, Emmi G, Lotan D, Marcolongo R, Lazaros G, De Biasio M, Cantarini L, Dagna L, Cercek AC, Pivetta E, Varma B, Berkson L, Tombetti E, Iannone F, Prisco D, Caforio ALP, Vassilopoulos D, Tousoulis D, De Luca G, Giustetto C, Rinaldi M, Oh JK, Klein AL, Brucato A, Adler Y. Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: The IRAP (International Registry of Anakinra for Pericarditis) study. Eur J Prev Cardiol. 2020 Jun;27(9):956-964. doi: 10.1177/2047487319879534. Epub 2019 Oct 15.

  PMID: 31610707 BACKGROUND

• Rasmussen LJH, Petersen JEV, Eugen-Olsen J. Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation. Front Immunol. 2021 Dec 2;12:780641. doi: 10.3389/fimmu.2021.780641. eCollection 2021.

  PMID: 34925360 BACKGROUND

• Hodges GW, Bang CN, Wachtell K, Eugen-Olsen J, Jeppesen JL. suPAR: A New Biomarker for Cardiovascular Disease? Can J Cardiol. 2015 Oct;31(10):1293-302. doi: 10.1016/j.cjca.2015.03.023. Epub 2015 Mar 25.

  PMID: 26118447 BACKGROUND

• Velissaris D, Zareifopoulos N, Koniari I, Karamouzos V, Bousis D, Gerakaris A, Platanaki C, Kounis N. Soluble Urokinase Plasminogen Activator Receptor as a Diagnostic and Prognostic Biomarker in Cardiac Disease. J Clin Med Res. 2021 Mar;13(3):133-142. doi: 10.14740/jocmr4459. Epub 2021 Mar 19.

  PMID: 33854652 BACKGROUND

• Pisacreta AM, Mascolo R, Nivuori M, Dominioni CC, Gabiati C, Trotta L, Pancrazi M, Marco GD, Carollo C, Pedroli A, Casarin F, Tombetti E, Bizzi E, Imazio M, Brucato A. Acute pericarditis with pleuropulmonary involvement, fever and elevated C-reactive protein: A systemic autoinflammatory disease? A cohort study. Eur J Intern Med. 2023 Jul;113:45-48. doi: 10.1016/j.ejim.2023.03.034. Epub 2023 Apr 15.

  PMID: 37069014 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be withdrawn to test: * IL-1RA Antibodies; * suPAR levels; * biochemical tests used in routine clinical practice, including complete blood count, biochemistry panel (C-reactive protein, urea, creatinine, sodium, potassium, chloride, calcium, magnesium, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, gamma-glutamyl transferase (gamma-GT), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), albumin, serum iron, transferrin, ferritin, triglycerides, cholesterol + HDL), and coagulation parameters (prothrombin time - PT, activated partial thromboplastin Time - aPTT, fibrinogen, D-dimer).

MeSH Terms

Conditions

Pericarditis

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Maddalena A Wu

  ASST Fatebenefratelli Sacco

  PRINCIPAL INVESTIGATOR

• Antonio L Brucato

  Fatebenefratelli Hospital

  STUDY DIRECTOR

Central Study Contacts

Maddalena A Wu

CONTACT

+393392883379; maddalena.wu@unimi.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 28, 2023
• First Posted: June 29, 2023
• Study Start: July 1, 2023
• Primary Completion: July 1, 2025
• Study Completion: December 20, 2025
• Last Updated: July 3, 2024

Record last verified: 2024-07

Locations

DE (3); IT (6)