An observational study in Pericarditis, sponsored by ASST Fatebenefratelli Sacco. Recruiting at 9 sites in 2 countries. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2024-07-03.
Sponsored by ASST Fatebenefratelli Sacco · Observational
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.
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.
54 studies on the registry are indexed under Pericarditis; 23 are open to participants now.
This study's planned enrollment of 146 is below the median of 300 across 25 observational studies indexed under Pericarditis.
Browse Pericarditis studies →ASST Fatebenefratelli Sacco is the lead sponsor of 38 studies on the registry; 12 are open to participants now.
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Consecutive patients with different phenotypes of pericarditis
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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.
Exclusion Criteria:
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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
-The measurement of anti-interleukin-1 receptor antagonist (IL1RA) antibodies will be performed using the ELISA (Enzyme-Linked Immunosorbent Assay) method,as previously described \[Thurner, L., et al., IL-1RA Antibodies in Myocarditis after SARS-CoV-2 Vaccination. N Engl J Med, 2022. 387(16): p. 1524-1527\].
-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.
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.
Time frame: 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.
Time frame: 24 months
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.
Time frame: 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.
Time frame: 24 months
Plan to share: Undecided
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ASST Fatebenefratelli Sacco