Clinical trial NCT06293924: Pericardial Fluid Analysis in Recurrent Pericarditis
Official title: The Pericardial Fluid Analysis in Recurrent Pericarditis Trial
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Acute Pericarditis
Pericardial Effusion
Pericardial Disease
Pericardial Fluid Exudate
Autoinflammatory Disorders
Autoinflammatory Disease
Keywords: Acute Pericarditis
Recurrent Pericarditis
Pericardial Effusion
Pericardiocentesis
Cardiac surgery
Cytofluorometry
Gene expression analysis
Autoinflammatory Disorders
Lead sponsor: ASST Fatebenefratelli Sacco
Sponsor class: OTHER
First posted: 2024-03-05
Enrollment: 432
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: For the first two arms, patients from the primary care clinic (Emergency room department). For the third arm, patients who need to undergo cardiac surgery with pericardial sac involvement.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Differences in cell counts among inflammatory and non-inflammatory pericardial effusion.
timeFrame: 48 months from patient's enrollment
measure: Difference in biochemical parameters among inflammatory and non-inflammatory pericardial effusion
timeFrame: 48 months from patient's enrollment
Secondary outcomes:
measure: Difference of IL-1 expression in pericardial fluid cells among inflammatory and non-inflammatory pericardial effusion
timeFrame: 48 months from patient's enrollment
measure: Differences of inflammatory cytokine expression in pericardial fluid cells among inflammatory and non-inflammatory pericardial effusion
timeFrame: 48 months from patient's enrollment
measure: Differences of gene expression in pericardial fluid cells among inflammatory and non-inflammatory pericardial effusion
timeFrame: 48 months from patient's enrollment
measure: Differences of gene expression in pericardial fluid and blood cells during pericarditis
timeFrame: 48 months from patient's enrollment
measure: Differences in cytokine and other molecule concentrations between pericardial fluid and blood cells in pericarditis
timeFrame: 48 months from patient's enrollment
measure: Correlation of inflammatory mediators in pericardial fluid and clinical features during pericarditis
timeFrame: 48 months from patient's enrollment
Other outcomes:
Locations:
city: Milan
country: Italy
facility: ASST FAtebenefratelli Sacco
state: Lombardia
Study officials:
affiliation: ASST Fatebenefratelli Sacco
name: Antonio Luca Brucato, Prof.
role: PRINCIPAL_INVESTIGATOR
References: