PericarditisPERIPLONCT05925790
Clinical Phenotypes in Pericarditis: IL-1RA Antibodies and suPAR Levels
An observational study of Pericarditis, run by ASST Fatebenefratelli Sacco at 9 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Pericarditis
- What is being tested?
- IL1RA Antibody Assay and suPAR Testing
- Type of treatment
- Vaccines
- How many people
- 146 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 1 Jul 2023to 20 Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Consecutive patients with different phenotypes of pericarditis
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
Italy6 sites, 6 recruiting
- Not yet recruiting
A.O.U. Careggi
Florence
Giacomo Emmi
Giacomo Emmi
- Recruiting
Luigi Sacco Hospital - ASST Fatebenefratelli Sacco
Milan, 20157
Maddalena A Wu, M.D., +393392883379, maddalena.ale.wu@gmail.com
Maddalena A Wu, maddalena.wu@unimi.it
- Recruiting
Fatebenefratelli Hospital - ASST Fatebenefratelli Sacco
Milan
Antonio Brucato
Antonio Brucato
- Not yet recruiting
Ospedale Galeazzi Sant'Ambrogio - IRCCS, Poliambulatorio Cardiovascolare Cardiologia Universitaria
Milan
Edoardo Conte
Edoardo Conte
- Not yet recruiting
Policlinico di Milano Ospedale Maggiore, Fondazione IRCCS Ca' Granda
Milan
Ferruccio Ceriotti
Ferruccio Ceriotti
- Not yet recruiting
Ospedale Santa Maria della Misericordia dell'ASU-FC
Udine
Massimo Imazio
Massimo Imazio
Germany3 sites, 3 recruiting
- Recruiting
Saarland University
Homburg
Lorenz Thurner
Lorenz Thurner
- Not yet recruiting
University Children's Hospital Muenster
Münster
Christoph Kessel
Christoph Kessel
- Not yet recruiting
University Hospital Tübingen
Tübingen
Karin Klingel
Karin Klingel
About this study
Official title: Observational Study on Anti-interleukin-1 Receptor Antagonist Antibodies and Soluble Urokinase Plasminogen Activator Receptor (suPAR) in Pericarditis: PERIPLO (PERicarditis: IL-1 RA Antibodies and suPAR Levels Observational) Study
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.
Read the detailed description
Recurrent pericarditis (RP) is a complex challenging condition, which significantly impacts patients' quality of life, both from the physical and emotional point of view, and can lead to dangerous complications such as cardiac tamponade and constrictive pericarditis. Moreover, patients experiencing several recurrences also tend to need substantial healthcare resources without necessarily experiencing clinical improvement. Understanding more into details the pathophysiology underlying RP is certainly of pivotal importance for optimizing workup strategies and treatment protocols. It is now recognized that pericarditis stems from a bidirectional cross-talk between environmental triggers and the innate and adaptive immune systems in a genetically susceptible host, with a central role of the pro-inflammatory agonistic molecule IL-1 (IL-1α and IL-1β) and the so-called inflammasome.
Neutralizing autoantibodies have been identified targeting the endogenous interleukin-1 receptor antagonist (IL-1RA) in conditions characterized by severe systemic inflammation such as myocarditis after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination, Coronavirus Disease (COVID-19) and Multisystem Inflammatory Syndrome (MIS-C). Therefore, it is possible to hypothesize that testing patients with RP for these antibodies might add significant insights into the knowledge of the pathophysiology of this condition. This may help uncover different underlying mechanisms with similar clinical presentations. New mechanisms involving hyperphosphorylation of IL-1RA precede peripheral immune tolerance breakdown, which may also contribute to certain pericarditis phenotypes.
Therefore, it is possible to hypothesize that IL-1RA antibody testing could provide important information to better profile RP patients with an inflammatory phenotype (as indicated by common biochemical markers like CRP) and those with a complicated clinical course. These patients often exhibit marked activation of the IL-1 signaling pathway, and IL-1RA antibody testing may help uncover underlying mechanisms and improve their characterization. Given the negative correlation between neutralizing antibodies against IL-1RA (and low circulating levels of IL-1RA) and markers of cardiac damage and inflammation, testing these antibodies in RP might be of value. High titers of IL-1RA antibodies in RP may indicate uncontrolled activation of the IL-1 pathway, shedding light on why some patients experience recurrences when tapering treatment with the naturally occurring IL-1 receptor antagonist, anakinra. Testing these IL-1RA antibodies in other types of pericarditis could also help explore their correlation with clinical phenotypes, including presentation, clinical course, and response to treatment strategies. Key exclusion criteria include pericarditis secondary to specific etiologies (except post-cardiac injury), history of immunosuppression, and any clinical conditions that may influence the results.
Additionally, suPAR testing can complementarily highlight chronic low-grade inflammation, which may underlie certain pericarditis cases that do not exhibit an overt "inflammatory phenotype" (e.g., normal CRP) but are challenging to manage.
Longitudinal testing of patients during acute episodes and intercritical phases is planned if feasible.
In both IL-1RA antibody and suPAR testing, this study aims to provide more accurate markers compared to commonly used markers for the "inflammatory phenotype" and potentially uncover unknown pathophysiological mechanisms. Currently, there is a lack of literature on this topic.
The results of this study may provide a rationale for the selective use of anakinra in specific clinical scenarios and/or guide the evaluation of its dosing with an individualized approach.
- Conditions
- Pericarditis
- Being tested
- IL1RA Antibody Assay, suPAR Testing
- Keywords
- Pericarditis, Anti-interleukin-1 receptor antagonist antibodies, Soluble urokinase plasminogen activator receptor, Pericarditis phenotypes
- Medical subject headings
- Pericarditis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL1RA Antibody AssayDiagnostic 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].
suPAR TestingDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: Diagnostic Test: IL1RA Antibody Assay; Diagnostic Test: suPAR Testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 24 months
Secondary outcomes (2)
Correlation of Time to Recurrence and Disease Activity with Anti-IL-1RA Antibodies in Pericarditis
- Correlate the time to recurrence with the levels of anti-IL-1RA antibodies.
- Correlate overall disease activity indices with the levels of anti-IL-1RA antibodies.
Measured: 24 months
Correlation of Time to Recurrence and Disease Activity with suPAR Levels in Pericarditis
- Correlate the time to recurrence with the levels of suPAR.
- Correlate overall disease activity indices with the levels of suPAR.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2023
- Study start1 Jul 2023
- Primary completion1 Jul 2025 (estimated)
- Study completion20 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for PericarditisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 146 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ASST Fatebenefratelli Sacco
- Sponsor type
- University, hospital or other
- Collaborators
- Fatebenefratelli Hospital, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Ospedale Galeazzi Sant'Ambrogio - IRCCS, Careggi Hospital, Azienda Ospedaliero Universitaria, Santa Maria della Misericordia di Udine, Italy, Children's Medical Hospital, University of Muenster, Muenster, Germany, University of Homburg, University Hospital Tuebingen
- Responsible party
- Principal investigator, Maddalena Alessandra Wu, ASST Fatebenefratelli Sacco
- Investigators
- Maddalena A Wu, Principal investigator, ASST Fatebenefratelli SaccoAntonio L Brucato, Study director, Fatebenefratelli Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05925790
- Sponsor's protocol ID
- 2023/ST/094
- Acronym
- PERIPLO
- Status last verified
- Jul 2024
- First submitted
- 28 May 2023
- Last updated
- 3 Jul 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 36130012Chiabrando 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.
PubMed 31918837Lopalco 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.
PubMed 32376492Mauro 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.
PubMed 33665514Adler 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.
PubMed 26320112Klein 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.
PubMed 34284595Brucato 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.
PubMed 27825009Imazio 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.
PubMed 31610707Rasmussen 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.
PubMed 34925360Hodges 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.
PubMed 26118447Velissaris 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.
PubMed 33854652Pisacreta 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.
PubMed 37069014
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study on Anti-interleukin-1 Receptor Antagonist Antibodies and Soluble Urokinase Plasminogen Activator Receptor (suPAR) in Pericarditis: PERIPLO (PERicarditis: IL-1 RA Antibodies and suPAR Levels Observational) Study
- ClinicalTrials.gov ID
- NCT05925790
- Acronym / sponsor ID
- PERIPLO / 2023/ST/094
- Conditions
- Pericarditis
- Keywords
- Pericarditis, Anti-interleukin-1 receptor antagonist antibodies, Soluble urokinase plasminogen activator receptor, Pericarditis phenotypes
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 146 participants (estimated)
- Lead sponsor
- ASST Fatebenefratelli SaccoUniversity, hospital or other
- Collaborators
- Fatebenefratelli Hospital, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Ospedale Galeazzi Sant'Ambrogio - IRCCS, Careggi Hospital, Azienda Ospedaliero Universitaria, Santa Maria della Misericordia di Udine, Italy, Children's Medical Hospital, University of Muenster, Muenster, Germany, University of Homburg, University Hospital Tuebingen
- Study start
- 1 Jul 2023 (actual)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 20 Dec 2025 (estimated)
- First posted
- 29 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Recurrent pericarditis (RP) is a complex challenging condition, which significantly impacts patients' quality of life, both from the physical and emotional point of view, and can lead to dangerous complications such as cardiac tamponade and constrictive pericarditis. Moreover, patients experiencing several recurrences also tend to need substantial healthcare resources without necessarily experiencing clinical improvement. Understanding more into details the pathophysiology underlying RP is certainly of pivotal importance for optimizing workup strategies and treatment protocols. It is now recognized that pericarditis stems from a bidirectional cross-talk between environmental triggers and the innate and adaptive immune systems in a genetically susceptible host, with a central role of the pro-inflammatory agonistic molecule IL-1 (IL-1α and IL-1β) and the so-called inflammasome.
Neutralizing autoantibodies have been identified targeting the endogenous interleukin-1 receptor antagonist (IL-1RA) in conditions characterized by severe systemic inflammation such as myocarditis after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination, Coronavirus Disease (COVID-19) and Multisystem Inflammatory Syndrome (MIS-C). Therefore, it is possible to hypothesize that testing patients with RP for these antibodies might add significant insights into the knowledge of the pathophysiology of this condition. This may help uncover different underlying mechanisms with similar clinical presentations. New mechanisms involving hyperphosphorylation of IL-1RA precede peripheral immune tolerance breakdown, which may also contribute to certain pericarditis phenotypes.
Therefore, it is possible to hypothesize that IL-1RA antibody testing could provide important information to better profile RP patients with an inflammatory phenotype (as indicated by common biochemical markers like CRP) and those with a complicated clinical course. These patients often exhibit marked activation of the IL-1 signaling pathway, and IL-1RA antibody testing may help uncover underlying mechanisms and improve their characterization. Given the negative correlation between neutralizing antibodies against IL-1RA (and low circulating levels of IL-1RA) and markers of cardiac damage and inflammation, testing these antibodies in RP might be of value. High titers of IL-1RA antibodies in RP may indicate uncontrolled activation of the IL-1 pathway, shedding light on why some patients experience recurrences when tapering treatment with the naturally occurring IL-1 receptor antagonist, anakinra. Testing these IL-1RA antibodies in other types of pericarditis could also help explore their correlation with clinical phenotypes, including presentation, clinical course, and response to treatment strategies. Key exclusion criteria include pericarditis secondary to specific etiologies (except post-cardiac injury), history of immunosuppression, and any clinical conditions that may influence the results.
Additionally, suPAR testing can complementarily highlight chronic low-grade inflammation, which may underlie certain pericarditis cases that do not exhibit an overt "inflammatory phenotype" (e.g., normal CRP) but are challenging to manage.
Longitudinal testing of patients during acute episodes and intercritical phases is planned if feasible.
In both IL-1RA antibody and suPAR testing, this study aims to provide more accurate markers compared to commonly used markers for the "inflammatory phenotype" and potentially uncover unknown pathophysiological mechanisms. Currently, there is a lack of literature on this topic.
The results of this study may provide a rationale for the selective use of anakinra in specific clinical scenarios and/or guide the evaluation of its dosing with an individualized approach.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inflammatory phenotype | – | Diagnostic Test: IL1RA Antibody Assay, Diagnostic Test: suPAR TestingPatients 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) |
| Non-inflammatory phenotype | – | Diagnostic Test: IL1RA Antibody Assay, Diagnostic Test: suPAR TestingPatients 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 |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Consecutive patients with different phenotypes of pericarditis
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IL1RA Antibody Assay-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]. | Diagnostic test | Inflammatory phenotype, Non-inflammatory phenotype |
| suPAR Testing-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. | Diagnostic test | Inflammatory phenotype, Non-inflammatory phenotype |
Primary outcome
Assessment of IL-1RA antibodies across pericarditis phenotypes
Time frame: 24 months
* Levels of anti-IL-1RA antibodies in different phenotypes of pericarditis. * Levels of anti-IL-1RA antibodies during acute episodes and intercritical phases.
Assessment of suPAR levels across pericarditis phenotypes
Time frame: 24 months
* Levels of suPAR in acute and recurrent pericarditis with normal C-reactive protein (CRP). * Levels of suPAR during acute episodes and intercritical phases.
2 secondary outcomes
Correlation of Time to Recurrence and Disease Activity with Anti-IL-1RA Antibodies in Pericarditis
Time frame: 24 months
Correlation of Time to Recurrence and Disease Activity with suPAR Levels in Pericarditis
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Background: PubMed 36130012Thurner 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.
- Background: PubMed 31918837Chiabrando 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.
- Background: PubMed 32376492Lopalco 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.
- Background: PubMed 33665514Mauro 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.
- Background: PubMed 26320112Adler 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.
- Background: PubMed 34284595Klein 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.
- Background: PubMed 27825009Brucato 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.
- Background: PubMed 31610707Imazio 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.
- Background: PubMed 34925360Rasmussen 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.
- Background: PubMed 26118447Hodges 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.
- Background: PubMed 33854652Velissaris 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.
- Background: PubMed 37069014Pisacreta 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maddalena A Wu principal investigator
ASST Fatebenefratelli Sacco
Antonio L Brucato study director
Fatebenefratelli Hospital
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pericarditis, run by ASST Fatebenefratelli Sacco at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maddalena A Wu (+393392883379, maddalena.wu@unimi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of IL-1RA antibodies across pericarditis phenotypes (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05925790, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.