Pericardial Fluid Analysis in Recurrent Pericarditis

• Conditions: Pericardial Disease; Pericardial Effusion; Pericardial Fluid Exudate; Acute Pericarditis; Autoinflammatory Disorders; Autoinflammatory Disease
• Interventions: Diagnostic Test: Pericardiocentesis; Diagnostic Test: Pericardiotomy; Diagnostic Test: Cytofluorometry and Gene expression analysis

• Registration Number: NCT06293924
• Lead Sponsor: ASST Fatebenefratelli Sacco

Brief Summary

This clinical trial aims to examine the biochemical and cytological features of pericardial effusion during acute and recurrent pericarditis and to understand the molecular factors responsible for pathogenesis. The primary objective of this study is to identify and validate diagnostic criteria in pericardial fluid analysis that can differentiate patients with acute and recurrent pericarditis from those with only pericardial fluid but no inflammation.

This study will enroll patients with acute pericarditis who require pericardiocentesis for either diagnostic or therapeutic purposes. Two control groups will also be included: one consisting of patients who need cardiac surgery with a collection of pericardial fluid, and the other consisting of patients who require pericardiocentesis for non-inflammatory pericardial effusion. The purpose of the study is to compare the cell activation status and cytokines present in pericardial fluid during acute pericarditis with those present during other pericardial pathologies.

Detailed Description

Idiopathic recurrent pericarditis is a condition characterized by recurrent inflammation of the pericardial sac and sometimes another serosa, accompanied by systemic signs and symptoms. Differential diagnosis of this condition includes all forms of pericarditis secondary to other diseases such as infections, autoimmune and autoinflammatory diseases, malignancy and other conditions (post-actinic, post-traumatic, post-pericardiotomy or post-infarct pericarditis, or those associated with metabolic dysregulations such as uremia). Some patients have pericardial effusion without any signs of inflammation: this condition is known as idiopathic pericardial effusion.

The analysis of pericardial effusion helps diagnostic and therapeutic decisions. European Society of Cardiology (ESC) guidelines recommend pericardial fluid analysis from pericardiocentesis or surgical access only whenever a suspected infectious or neoplastic form. Pericardiocentesis is also a procedure used to remove excess fluid from the sac surrounding the heart with hemodynamic effects on ventricular diastolic filling. It is performed in emergencies such as cardiac tamponade to relieve pressure on the heart.

The causes and mechanisms of idiopathic pericarditis are not yet well understood. However, studies have shown that colchicine, a medication used to treat this condition, can prevent the formation of microtubules, the migration of neutrophils, and the formation of the NLRP3 inflammasome. These factors have been suggested to play a role in the development of this disease. In addition, research has focused on the use of Anakinra, an anti-interleukin 1 (IL-1) drug, in the treatment of acute pericarditis. This confirms the possible involvement of IL-1 beta in this disease. It is produced by the activation of a complex called NLRP3 inflammasome, which is triggered by microbial products (PAMPs), urate crystals, cholesterol, and molecules known as damage-associated molecular patterns (DAMPs). Therapeutic options for idiopathic pericarditis include colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), steroids, and IL-1 antagonists to regulate inflammation and leukocyte migration.

This study focuses on two main unmet needs related to acute and recurrent pericarditis. The first need is related to the informativeness of the data obtained through pericardiocentesis. Although the biochemical analysis is recommended by ESC guidelines, the most valuable data in the diagnostic process comes from cytological and microbiological analyses. These analyses help in excluding neoplastic or infectious etiologies. Biochemical features of pericardial fluid are less understood than those of peritoneal and pleural fluids. Specific biochemical parameters used to distinguish exudation as Light's criteria do not apply to pericardial fluid: a previous study showed a unique composition of pericardial fluid, which suggests that Light's criteria cannot be used in this case. The second unsatisfied need is related to pathogenesis, including the pathway of Interleukin-1 (IL-1) at the level of pericardial fluid and which cells are responsible for local cytokines and inflammatory mediators productions.

This study aims to collect observational data on pericardial effusion analysis and to analyse cellular and molecular composition in a subgroup of patients to assess the pathophysiological mechanisms of disease.

Study Timeline

• Study First Submitted: 2024-02-26
• Study First Submitted QC: 2024-03-02
• Study First Posted: 2024-03-05
• Study Start: 2024-08-18
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-25
• Last Update Posted: 2024-11-27
• Primary Completion: 2029-02
• Study Completion: 2031-02

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 432

Inclusion Criteria

• Patients with acute idiopathic or post-cardiac injury pericarditis who require diagnostic or therapeutic pericardiocentesis (Interventional arm)
• Subjects with non-inflammatory pericardial effusion who require diagnostic or therapeutic pericardiocentesis (First control arm)
• Patients who undergo cardiac surgery that involves a pericardiotomy (Second control arm)

Exclusion Criteria

• Pregnancy or breastfeeding
• Ongoing infections, including active viral hepatitis or Coronavirus Disease 19 (COVID-19) positivity in the previous 21 days
• Systemic inflammatory disorders not attributable to pericarditis, excluding inflammatory diseases in remission
• Solid or haematological malignancies, ongoing or less than 6 months disease-free interval or anti-blastic chemotherapy (excluding the hormone therapy)
• Immunosuppressive therapy for reasons other than pericarditis treatment.
• Moderate-severe kidney failure (GFR < 30 ml/min)
• Moderate-severe liver failure (Child-Pug B or C), active hepatitis
• Diabetes mellitus
• Severe hypoproteinemia/malnutrition

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Pericardial effusion patients without inflammation	Pericardiocentesis	Subjects with non-inflammatory pericardial effusion who require diagnostic or therapeutic pericardiocentesis. Four ml of pericardial fluid should be collected: 2 ml for biochemical analysis in lithium heparin or serum-gel separator-associated tubes, and 2 ml for cellular analysis in K3 EDTA tubes.
Pericarditis patients	Pericardiocentesis	Patients with acute idiopathic or post-cardiac injury pericarditis who require diagnostic or therapeutic pericardiocentesis. Four ml of pericardial fluid should be collected: 2 ml for biochemical analysis in lithium heparin or serum-gel separator-associated tubes, and 2 ml for cellular analysis in K3 ethylenediaminetetraacetic acid (K3-EDTA) tubes.
Pericarditis patients	Cytofluorometry and Gene expression analysis	Patients with acute idiopathic or post-cardiac injury pericarditis who require diagnostic or therapeutic pericardiocentesis. Four ml of pericardial fluid should be collected: 2 ml for biochemical analysis in lithium heparin or serum-gel separator-associated tubes, and 2 ml for cellular analysis in K3 ethylenediaminetetraacetic acid (K3-EDTA) tubes.
Cardiac surgery pericardial effusion	Cytofluorometry and Gene expression analysis	Patients who undergo cardiac surgery that involves a pericardiotomy. During cardiac surgery, 4 ml of pericardial fluid is collected and analyzed upon opening the pericardial sac. Four ml of pericardial fluid should be collected: 2 ml for biochemical analysis in lithium heparin or serum-gel separator-associated tubes, and 2 ml for cellular analysis in K3 EDTA tubes.
Pericardial effusion patients without inflammation	Cytofluorometry and Gene expression analysis	Subjects with non-inflammatory pericardial effusion who require diagnostic or therapeutic pericardiocentesis. Four ml of pericardial fluid should be collected: 2 ml for biochemical analysis in lithium heparin or serum-gel separator-associated tubes, and 2 ml for cellular analysis in K3 EDTA tubes.
Cardiac surgery pericardial effusion	Pericardiotomy	Patients who undergo cardiac surgery that involves a pericardiotomy. During cardiac surgery, 4 ml of pericardial fluid is collected and analyzed upon opening the pericardial sac. Four ml of pericardial fluid should be collected: 2 ml for biochemical analysis in lithium heparin or serum-gel separator-associated tubes, and 2 ml for cellular analysis in K3 EDTA tubes.

Primary Outcome Measures

Name	Time	Method
Differences in cell counts among inflammatory and non-inflammatory pericardial effusion.	48 months from patient's enrollment	Both automated cytometry and manual counting were used to obtain absolute and relative cell counts from peripheral blood samples and pericardial fluids. It can help identify and establish diagnostic criteria for distinguishing between patients with acute or recurrent pericarditis and those with non-inflammatory pericardial fluid.
Difference in biochemical parameters among inflammatory and non-inflammatory pericardial effusion	48 months from patient's enrollment	This analysis evaluates the differences in pericardial fluid and peripheral blood among biochemical parameters (total proteins and albumin, lactate dehydrogenase, blood glucose, and cholesterol concentrations). It can help distinguish between patients with acute or recurrent pericarditis and those with non-inflammatory pericardial fluid, thereby aiding in the validation of diagnostic criteria.

Secondary Outcome Measures

Name	Time	Method
Differences of inflammatory cytokine expression in pericardial fluid cells among inflammatory and non-inflammatory pericardial effusion	48 months from patient's enrollment	A flow cytometry analysis is performed to assess absolute and relative cell counts expressing inflammatory cytokines in pericardial fluid for the differentiation between pericarditis and non-inflammatory pericardial fluid.
Differences of gene expression in pericardial fluid and blood cells during pericarditis	48 months from patient's enrollment	A gene expression analysis evaluates the increase of activated inflammatory cells in pericarditis through absolute and relative cell counts in pericardial fluid and blood samples using transcribed RNA. This analysis can confirm the correlation between activated inflammatory cells in pericardial and blood samples during pericarditis.
Difference of IL-1 expression in pericardial fluid cells among inflammatory and non-inflammatory pericardial effusion	48 months from patient's enrollment	A flow cytometry analysis is performed to assess absolute and relative cell counts expressing IL-1 in pericardial fluid for the differentiation between pericarditis and non-inflammatory pericardial fluid.
Differences of gene expression in pericardial fluid cells among inflammatory and non-inflammatory pericardial effusion	48 months from patient's enrollment	A gene expression analysis using transcribed RNA assesses absolute and relative cell counts expressing inflammatory cytokines in pericardial fluid and blood samples for the differentiation between pericarditis and non-inflammatory pericardial fluid.
Correlation of inflammatory mediators in pericardial fluid and clinical features during pericarditis	48 months from patient's enrollment	Biochemical analysis evaluates the increase of inflammatory cytokines and other molecules in pericarditis in pericardial fluid and blood samples. This analysis can confirm the correlation between cytokines and other molecules and clinical manifestations during pericarditis.
Differences in cytokine and other molecule concentrations between pericardial fluid and blood cells in pericarditis	48 months from patient's enrollment	Biochemical analysis evaluates the increase of inflammatory cytokines and other molecules in pericarditis in pericardial fluid and blood samples using normal methods of analysis. This analysis can confirm the correlation between inflammatory mediators in pericardial and blood samples during pericarditis.

Trial Locations

Locations (1)

ASST FAtebenefratelli Sacco; 🇮🇹 Milan, Lombardia, Italy