Pericarditis Clinical Trial
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.
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. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Not yet recruiting |
NCT03253315 -
Management of Pericarditis in Children.
|
N/A | |
Recruiting |
NCT02754713 -
Prognostic Biomarkers in Patients With Acute Pericarditis
|
N/A | |
Completed |
NCT00235079 -
Study of Colchicine to Treat and Prevent Recurrent Pericarditis After Failure of Conventional Treatment.
|
Phase 4 | |
Completed |
NCT04906720 -
Post-Ablation Pericarditis Reduction Study
|
Phase 2 | |
Not yet recruiting |
NCT05805930 -
Therapeutic Approach in Colchicine-resistant Recurrent pEricarditis in Children
|
Phase 3 | |
Not yet recruiting |
NCT06411340 -
Inflammation in Acute Cardiovascular Diseases - the CArdiovascular Inflammation Registry (CAIR)
|
||
Terminated |
NCT00946907 -
Benign Acute Pericarditis: Brief Versus Longer Treatment Using Aspirin
|
Phase 4 | |
Recruiting |
NCT04294771 -
JOint Use of Database to Identify Risk Factors of CARDio-vascular Toxicity Induced by Immune Checkpoint Inhibitors
|
||
Enrolling by invitation |
NCT04774549 -
Inflammatory Cardiomyopathy Bern Registry
|
||
Completed |
NCT02083510 -
Apolipoprotein CIII Reduction Via Colchicine
|
Phase 0 | |
Enrolling by invitation |
NCT01063582 -
Noise, a Risk for Heart in Airplane Pilots
|
N/A | |
Completed |
NCT04692766 -
Study to Evaluate the Efficacy and Safety of RPH-104 Treatment in Patients With Idiopathic Recurrent Pericarditis
|
Phase 2/Phase 3 | |
Active, not recruiting |
NCT03231449 -
A Survey of Hospitalizations in Cardiology Units in Sub-Saharan Africa
|
||
Completed |
NCT00128414 -
Study of Colchicine to Treat and Prevent Recurrent Pericarditis (First Episode)
|
Phase 3 | |
Completed |
NCT00128453 -
Study of Colchicine to Treat Acute Pericarditis and Prevent Recurrences
|
Phase 3 | |
Recruiting |
NCT05046002 -
COVID-19 Vaccine-induced Inflammatory Heart Disease Prevalence Registry
|
||
Recruiting |
NCT06103123 -
MYocarditis and/or Pericarditis Following mRNA COVID-19 VACCination National Surveillance Study
|
||
Completed |
NCT01395082 -
ACAM2000® Myopericarditis Registry
|