AnakInRa for Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP)

NCT02219828 | Completed Phase 4 DMC

• 2 other identifiers: 40/08/132013-001849-13
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Idiopathic Recurrent Pericarditis

Keywords

pericarditis; recurrent pericarditis; corticosteroids; anakinra

Outcome Measures

Primary Outcomes (1)

• Recurrence rate

  Time to flare in the anakinra and placebo arms

  8 months

Secondary Outcomes (8)

• 1. responder status in the open label phase

  60 days

• 2. change over time of the 3 outcome criteria, i.e. pericardial pain, CRP levels, and echocardiographic effusion;

  8 months

• 3. time to response in the open label phase

  8 months

• 4. percentage of patients who relapse in the withdrawal part in the two arms;

  8 months

• 5. change over time in patient's/parent's global assessment of overall well being on a 21 circle VAS;

  8 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

placebo sc

Drug: Placebo

Anakinra

ACTIVE COMPARATOR

Anakinra 2mg/Kg up to 100mg (maximum dose)

Drug: Anakinra

Interventions

Anakinra DRUG

2mg/Kg daily sc up to 100mgday as maximum dose

Anakinra

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 5 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age \> 2 years and \<70 years at screening visit;
• 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).
• Specific etiologies excluded, including tuberculous, neoplastic or purulent etiologies, post-cardiac injury syndromes, and rheumatic autoimmune diseases.
• 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.
• Troponin values during at least one previous attack is recorded.
• QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative (PPD) test has been previously made and recorded.
• 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)
• Continuous treatment with CS, the dose of which must not have been increased in the three days preceding enrolment
• 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.

You may not qualify if:

• Patients fulfilling any of the following criteria are not eligible for enrollment in this study:
• 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).
• History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result.
• 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.
• 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.
• 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
• 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.)
• History of recurrent and/or evidence of active bacterial, fungal, or viral infection(s).
• History of Type I hypersensitivity to anakinra.
• History of poor compliance.
• Use of any investigational drug (or biologic), or device within five half-lives of the drug prior to study entry or during the study.

Sponsors & Collaborators

• Massimo Imazio: lead

Study Sites (3)

Internal Medicine Division, OSpedale Papa Giovanni XXIII

Bergamo, Bergamo, 24100, Italy

Location

Pediatric Dept. Ospedale Gaslini

Genova, Genova, 16100, Italy

Location

Cardiology Dpt, Maria Vittoria Hospital

Torino, Torino, 10141, Italy

Location

Related Publications (1)

• Brucato A, Imazio M, Gattorno M, Lazaros G, Maestroni S, Carraro M, Finetti M, Cumetti D, Carobbio A, Ruperto N, Marcolongo R, Lorini M, Rimini A, Valenti A, Erre GL, Sormani MP, Belli R, Gaita F, Martini A. Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial. JAMA. 2016 Nov 8;316(18):1906-1912. doi: 10.1001/jama.2016.15826.

  PMID: 27825009 DERIVED

MeSH Terms

Conditions

Pericarditis

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Cardiology Dpt ASLTO2

Study Record Dates

• First Submitted: August 14, 2014
• First Posted: August 19, 2014
• Study Start: June 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: October 1, 2015
• Last Updated: December 18, 2015

Record last verified: 2015-12

Locations

IT (3)