AnakInRa Treatment of Recurrent Idiopathic Pericarditis

Phase 1

• Conditions: idiopathic recurrent pericarditis; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2013-001849-13-IT
• Lead Sponsor: ASLTO2-Maria Vittoria Hospital Cardiology

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-10-05
• Last Update Posted: 28 November 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Patients eligible for inclusion in this study have to fulfill all of the following criteria:

1.Patient’s written informed consent for = 18 years of age before any assessment is performed. Parents’ or legal guardian’s written informed consent and child’s assent, if appropriate, are required before any assessment is performed for patients < 18 years of age.
2.Age > 2 years and <70 years at screening visit;
3.Recurrent pericarditis defined as a first episode of acute pericarditis followed by recurrences (Ann Intern Med. 2011;155:409-14) (at least two recurrences for this study). First episode of
pericarditis is diagnosed when at least two of the following criteria were present: pericarditic typical chest pain (sharp and pleuritic, improved by sitting up and leaning forward), pericardial friction rubs, widespread ST segment elevation or PR depressions not previously reported, and new or worsening pericardial effusion. Recurrence is diagnosed when chest pain recurs and one or more of the following signs is present: fever, pericardial friction rub, ECG changes, echocardiographic evidence of new or worsening pericardial effusion, and elevations in the white blood cell count, erythrocyte sedimentation rate or C-reactive protein. To be enrolled in this study, elevation of C-reactive protein is mandatory both in the first attack and in the following recurrences. We differentiate recurrences from incessant pericarditis, term used to define patients with continued activity of pericarditis (with a symptom-free interval of < 6 weeks) (Soler-Soler J, Sagristà-Sauleda J, Permanyer-Miralda G. Relapsing pericarditis. Heart. 2004;90:1364-8).
4.Specific etiologies excluded, including tuberculous, neoplastic or purulent etiologies, post-cardiac injury syndromes, systemic diseases including rheumatic autoimmune diseases and autoinflammatory diseases such as familial Mediterranean fever (FMF) and tumour necrosis factor receptor-associated periodic syndrome (TRAPS).
5.Records to document the number of prior pericardial recurrences, the time interval between them as well as prior treatments must be made available from the medical charts.
6.Troponin values during at least one previous attack is recorded.
7.QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative (PPD) test has been previously made and recorded.
8.Patients will be enrolled at the time of a recurrent episode (at least the second recurrence, i.e. third episode) or relapse” of pericarditis documented by the following criteria:

-recurrent pericardial pain (with a score of least 5 on the 21 circles VAS) AND
-increase in CRP >1 mg/dL (being normal value = 0 - 0.5 mg/dL ), AND
-one or more of the following signs: fever (= 37°C), pericardial friction rub, pertinent ECG changes, echocardiographic evidence of of new or worsening pericardial effusion (see definition above)

9.Continuous treatment with CS, the dose of which must not have been increased in the three days preceding enrolment
10.Women of child bearing potentials (WCBP), defined as pre-menarche females aged 8 years and above or all women physiologically capable of becoming pregnant, sexually active, must use an effective form of contraception. Medically approved contraception (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices) could include total abstine

Exclusion Criteria

Patients fulfilling any of the following criteria are not eligible for enrollment in this study:
1.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
2.History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result.
3.Positive QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative (PPD) test (= 5 mm induration) performed after the first attack of pericarditis. Patients with a positive PPD test (= 5 mm induration) at screening may be enrolled only if they have either a negative chest X-ray or a negative QuantiFERON test.
4.Live vaccinations within three months prior to the start of the trial, during the trial, and up to three months following the last anakinra dose.
5.History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
6.History of significant other medical conditions, which in the Investigator’s opinion would exclude the patient from participating in this trial including current pericarditis due to known diseases (e.g. tuberculosis, neoplastic or purulent causes, connective tissue diseases, acute rheumatic fever, etc.)
7.History of recurrent and/or evidence of active bacterial, fungal, or viral infection(s).
8.History of Type I hypersensitivity to anakinra.
9.History of poor compliance.
10.Use of any investigational drug (or biologic), or device within five half-lives of the drug prior to study entry or during the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Recent findings suggest that idiopathic recurrent pericarditis (RP) may be a previously unrecognized autoinflammatory disease. The pivotal pathogenic role of interleukin (IL)-1 in RP has been demonstrated by the achievement of complete responses after treatment with the recombinant IL-1–receptor antagonist, anakinra. Anakinra is the recombinant form of IL-1Ra. The proposed study is designed to demonstararte the efficacy of anakinra in idiopathic RP.;Secondary Objective: To assess CS and concurrent medication sparing effects of anakinra over 8 months;Primary end point(s): Time to flare in the anakinra and placebo arms in the withdrawal phase;Timepoint(s) of evaluation of this end point: 8 months