Therapy Management in Patients Treated With Anakinra Due to Recurrent Pericarditis

Sponsor

Azienda Ospedaliero, Universitaria Ospedali Riuniti (Other)

Overall Status

Recruiting

CT.gov ID

NCT06071156

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To determine the utility of serial cardiac magnetic resonance (CMR) imaging for guidance of therapy management in patients treated with anakinra due to recurrent pericarditis (RP), compared with c-reactive protein (CRP) assay alone.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Pericarditis	Drug: Anakinra	N/A

Detailed Description

Recurrent pericarditis (RP) is a specific pathology of the pericardium included within the pericardial syndromes by the guidelines of the European Society of Cardiology (ESC). The latter defines RP as pericarditis occurring after a symptom-free interval of 4-6 weeks from a documented first episode of acute pericarditis; the recurrences rate may range from 15 to 30%, with a significant increment of 50% in patients treated with corticosteroids or not treated with colchicine. The diagnosis of recurrences follows the same criteria utilized for acute pericarditis, and a viral etiology can often be demonstrated.

The pathogenesis of RP is still debated, but they are self-sustained by an autoinflammatory/ autoimmune amplified response following an exogenous or endogenous trigger. In this context, the cytokine interleukin 1 (IL-1) has been implicated as a key mediator of RP. Anakinra, an IL-1 antagonist, is of particular interest because it limits the self-sustained pathway of RP and may reduce the recurrences. The current 2015 ESC guidelines for the diagnosis and management of pericardial diseases recommend anakinra in cases of proven infection-negative, corticosteroid-dependent RP not responsive to colchicine, but it remains debated the duration of the therapy and when to start its tapering. In this context, cardiac magnetic resonance (CMR) imaging has recently emerged as an interesting imaging biomarker capable of detecting pericardial inflammation, proving pericardial edema and late gadolinium enhancement (LGE), and distinguishing three defined pericardial inflammation phases: acute (edema and LGE), subacute (only LGE) and burned-out (no edema nor LGE).

To overcome the 2015 ESC guidelines limitations, the investigators sought to determine the utility of serial CMR imaging for guidance of therapy management in patients treated with anakinra due to RP, compared with the c-reactive protein (CRP) assay alone, as currently recommended.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

1:1 randomization1:1 randomization

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Serial Cardiac Magnetic Resonance Imaging for Guidance of Therapy Management in Patients Treated With Anakinra Due to Recurrent Pericarditis

Actual Study Start Date :

Jan 1, 2018

Actual Primary Completion Date :

May 5, 2022

Anticipated Study Completion Date :

Jan 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CMR-guided therapy management, The scheme of Anakinra treatment was three months at full dosage, the next three months of therapy at full dosage every other day, and the last three months at halved dosage every other day until the end of treatment. Cardiac magnetic resonance [no pericardial edema and/or late gadolinium enchantment (LGE)] guided each anakinra dose reduction. If the tests were positive for ongoing pericardial inflammation [pericardial edema present or LGE present], the reduction was postponed, and one more month of therapy was administered before the reduction.	Drug: Anakinra Anakinra, an IL-1 antagonist, is particularly interesting because it limits the self-sustained pathway of recurrent pericarditis and may reduce the recurrences
Active Comparator: CRP-guided therapy management, The scheme of Anakinra treatment was three months at full dosage, the next three months of therapy at full dosage every other day, and the last three months at halved dosage every other day until the end of treatment. Laboratory tests [C-reactive protein (CRP) <0.6 mg/dL] guided each anakinra dose reduction. If the tests were positive for ongoing systemic inflammation (CRP > 0.6 mg/dL), the reduction was postponed, and one more month of therapy was administered before the reduction.	Drug: Anakinra Anakinra, an IL-1 antagonist, is particularly interesting because it limits the self-sustained pathway of recurrent pericarditis and may reduce the recurrences

Arm

Intervention/Treatment

Active Comparator: CMR-guided therapy management,

The scheme of Anakinra treatment was three months at full dosage, the next three months of therapy at full dosage every other day, and the last three months at halved dosage every other day until the end of treatment. Cardiac magnetic resonance [no pericardial edema and/or late gadolinium enchantment (LGE)] guided each anakinra dose reduction. If the tests were positive for ongoing pericardial inflammation [pericardial edema present or LGE present], the reduction was postponed, and one more month of therapy was administered before the reduction.

Drug: Anakinra

Anakinra, an IL-1 antagonist, is particularly interesting because it limits the self-sustained pathway of recurrent pericarditis and may reduce the recurrences

Active Comparator: CRP-guided therapy management,

The scheme of Anakinra treatment was three months at full dosage, the next three months of therapy at full dosage every other day, and the last three months at halved dosage every other day until the end of treatment. Laboratory tests [C-reactive protein (CRP) <0.6 mg/dL] guided each anakinra dose reduction. If the tests were positive for ongoing systemic inflammation (CRP > 0.6 mg/dL), the reduction was postponed, and one more month of therapy was administered before the reduction.

Drug: Anakinra

Anakinra, an IL-1 antagonist, is particularly interesting because it limits the self-sustained pathway of recurrent pericarditis and may reduce the recurrences

Outcome Measures

Primary Outcome Measures

Recurrences of pericarditis [6 month]
Recurrences of pericarditis during Anakinra reduction regimen of therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients treated with anakinra 100 mg/die if ≥ 18 years old, and
Pediatric patients treated with anakinra 2 mg/kg/die if < 18 years old
Pediatric and adult patients treated with anakinra due to corticosteroid-dependent or not responsive to colchicine or non-steroidal anti-inflammatory drugs (NSAIDs) recurrent pericarditis