AnakInRa for Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP)
AnakInRa for Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP)
Recent findings suggest that recurrent pericarditis (RP) may be a previously unrecognized
 autoinflammatory disease. The pivotal pathogenic role of interleukin (IL)-1 in RP has been
 shown 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 demonstarate the efficacy of anakinra in RP.
This is a 8-month, multicenter (3 Italian centers), randomized, double-blind,
 placebo-controlled, multicenter, medication-withdrawal study to evaluate the efficacy,
 tolerability, and safety of anakinra in adults and children with idiopathic recurrent
 pericarditis (RP).
Inclusion 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, and rheumatic autoimmune diseases.

 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 abstinence. Reliable contraception should be
 maintained throughout the study and for 3 months after anakinra discontinuation. Women
 are considered post-menopausal and not WCBP if they have had 12 months of natural
 (spontaneous) amenorrhea with an appropriate clinical profile (e.g. appropriate age,
 history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH
 levels > 40 mIU/mL or have had surgical bilateral oophorectomy (with or without
 hysterectomy) at least six weeks prior to study entry. In the case of oophorectomy
 alone, only when the reproductive status of the woman has been confirmed by follow up
 hormone level assessment she considered a WCBP.

 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.