Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT05805930 |
Other study ID # |
CREATE |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
Phase 3
|
First received |
|
Last updated |
|
Start date |
June 1, 2023 |
Est. completion date |
May 31, 2026 |
Study information
Verified date |
April 2023 |
Source |
Istituto Giannina Gaslini |
Contact |
Roberta Caorsi, MD |
Phone |
+39 010 56362916 |
Email |
robertacaorsi[@]gaslini.org |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to demonstrate that anakinra provides more rapid disease control
than steroids in the first month of treatment in the event of recurrent pericarditis and is
more effective in preventing further exacerbations in patients aged between eight months and
eighteen years of age with idiopathic or post-procedural pericarditis, unresponsive to
first-line treatment with NSAIDs and colchicine at the appropriate dosage, or in case of
colchicine intolerance. The efficacy of the two treatments will be evaluated by the capacity
and timing of the two therapies to determine a complete control (clinical, laboratory and
instrumental) of the disease and the absence of recurrences.
Description:
Although steroids represent the second-line treatment for recurrent pericarditis (RP), to be
used in case of inadequate response to NSAIDs and colchicine, their use is controversial due
to their side effects.
Indeed, in adult patients with RP it has been demonstrated that the use of steroids is
associated with an increased risk of recurrence: in a study carried out in adult patients,
64% of patients taking high-dose steroids (> 1 mg/kg/ of prednisone or equivalent), and 32%
of patients taking this low-dose drug (< 1 mg/kg/day of prednisone or equivalent) relapsed.
Furthermore, the therapy is associated with serious side effects and an increased risk of
hospitalization, especially in patients treated with high doses. Finally, a high percentage
of RP patients (both adult and pediatric) treated with steroids tend to become
steroid-dependent, experiencing a disease exacerbation during tapering of treatment or soon
after its discontinuation. The side effects associated with the chronic use of steroids are
well known, especially in childhood, as their use is associated not only with reduced bone
density, but also with growth retardation. Therefore, their long-term use is contraindicated,
especially in children.
In a recent retrospective study of 58 pediatric patients with recurrent pericarditis treated
with IL-1 inhibitors, a high steroid dependence rate was observed (45 of 48 treated
patients). In this study, the presence of predictive factors associated with the possibility
of achieving long-term remission was evaluated. Unfortunately, it could not be shown that
avoiding steroid use was associated with an increased chance of withdrawing anakinra without
relapse. This is likely due to the large variability of the cohort included in the
retrospective study.
Therapy with anakinra in recurrent pericarditis is aimed at obtaining rapid and complete
control of the disease and maintaining it over time, allowing the suspension of steroid
therapy and thus reducing the risk of complications, chronicity and recurrence.
In the field of pediatric rheumatology, there is convincing evidence that in children with
chronic arthritis a more aggressive therapy at an early stage can take advantage of the
so-called "window of opportunity": according to this theory, early biological treatment can
modify the pathogenetic mechanism of the disease by improving its long-term outcomes.
In particular, it has been shown that anakinra therapy in children with systemic JIA can lead
to rapid attainment of inactive disease and allow for early discontinuation of treatment in
the absence of recurrence in the majority of patients. Among all the rheumatological
pathologies of the pediatric age, systemic JIA is the one that has the greatest similarities
with autoinflammatory diseases due to the presence of fever, sometimes recurrent, rash and
serositis, typical characteristics of AID, especially of inflammasomopathies. Recurrent
pericarditis itself has many similarities to these conditions, as demonstrated by the
efficacy of interleukin-1 inhibition. In fact, both of these conditions are considered by
many to be real autoinflammatory diseases, with a multifactorial etiology. It is therefore
reasonable to think that the concept of the "window of opportunity" can also be translated to
recurrent pericarditis: the early blockade of cytokines could in fact abrogate the
pathogenetic mechanism of the disease and therefore its chronic course and/or its relapses.