AnakInRa for Treatment of Recurrent Idiopathic Pericarditis (AIR TRIP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Maria Vittoria Hospital
Sponsor:
Information provided by (Responsible Party):
Massimo Imazio, Maria Vittoria Hospital
ClinicalTrials.gov Identifier:
NCT02219828
First received: August 14, 2014
Last updated: August 17, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Idiopathic Recurrent Pericarditis
Drug: Anakinra
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: AnakInRa for Treatment of Recurrent Idiopathic Pericarditis

Resource links provided by NLM:


Further study details as provided by Maria Vittoria Hospital:

Primary Outcome Measures:
  • Recurrence rate [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Time to flare in the anakinra and placebo arms


Secondary Outcome Measures:
  • 1. responder status in the open label phase [ Time Frame: 60 days ] [ Designated as safety issue: No ]

    To assess the responder status in the open label phase at Day 8 and 60 and at the end of the study with the following three criteria all to be met:

    1. no or mild pericardial pain (a score ≤2.5 on a 21 circle VAS), AND
    2. normal CRP levels (CRP ≤0.5 mg/dL), AND
    3. absent or mild (≤10 mm) echocardiographic effusion. Assessments will be performed at Days 4, and 8 (study Period 1), and then at Day 30, and Months 2, 4, 6, and 8 if not otherwise specified.

  • 2. change over time of the 3 outcome criteria, i.e. pericardial pain, CRP levels, and echocardiographic effusion; [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Assessments will be performed at Days 4, and 8 (study Period 1), and then at Day 30, and Months 2, 4, 6, and 8 if not otherwise specified.

  • 3. time to response in the open label phase [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Assessments will be performed at Days 4, and 8 (study Period 1), and then at Day 30, and Months 2, 4, 6, and 8 if not otherwise specified.

  • 4. percentage of patients who relapse in the withdrawal part in the two arms; [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Assessments will be performed at Days 4, and 8 (study Period 1), and then at Day 30, and Months 2, 4, 6, and 8 if not otherwise specified.

  • 5. change over time in patient's/parent's global assessment of overall well being on a 21 circle VAS; [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Assessments will be performed at Days 4, and 8 (study Period 1), and then at Day 30, and Months 2, 4, 6, and 8 if not otherwise specified.

  • 6. change over time in the global evaluation of disease activity by physicians on a 21 circle VAS [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
    Assessments will be performed at Days 4, and 8 (study Period 1), and then at Day 30, and Months 2, 4, 6, and 8 if not otherwise specified.

  • 7. change over time in quality of life as assessed by the SF-36 scale in adults and by the CHQ in children [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Assessments will be performed at Days 4, and 8 (study Period 1), and then at Day 30, and Months 2, 4, 6, and 8 if not otherwise specified.

  • 8. percentage off CS and any other concurrent medication at 6weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Assessments will be performed at Days 4, and 8 (study Period 1), and then at Day 30, and Months 2, 4, 6, and 8 if not otherwise specified.

  • 9. tolerability and safety of the treatment [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
    To assess the tolerability and safety of the treatment, i.e. monitoring and recording all adverse events (AEs), with attention to local tolerability to s.c. injection, and serious adverse events (SAEs), and the regularly scheduled monitoring of hematology, blood chemistry, physical examinations, and vital signs including blood pressure over 8 months. Assessments will be performed at Days 4, and 8 (study Period 1), and then at Day 30, and Months 2, 4, 6, and 8 if not otherwise specified.


Estimated Enrollment: 20
Study Start Date: June 2014
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
placebo sc
Drug: Placebo
Placebo
Active Comparator: Anakinra
Anakinra 2mg/Kg up to 100mg (maximum dose)
Drug: Anakinra
2mg/Kg daily sc up to 100mgday as maximum dose
Other Name: Anakinra

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   5 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, 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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02219828

Contacts
Contact: Massimo Imazio, MD +39011439 ext 3423 massimo_imazio@yahoo.it
Contact: Arcangela Pane +39011439 ext 3315 pane@aslto2.piemonte.it

Locations
Italy
Internal Medicine Division, OSpedale Papa Giovanni XXIII Recruiting
Bergamo, Italy, 24100
Contact: Antonio Brucato, MD       albrucato@hpg23.it   
Principal Investigator: Antonio Brucato, MD         
Pediatric Dept. Ospedale Gaslini Recruiting
Genova, Italy, 16100
Contact: Alberto Martini, MD       albertomartini@ospedale-gaslini.ge.it   
Principal Investigator: Alberto Martini, MD         
Cardiology Dpt, Maria Vittoria Hospital Recruiting
Torino, Italy, 10141
Contact: Massimo Imazio, MD    +39011439 ext 3423    massimo_imazio@yahoo.it   
Principal Investigator: Massimo Imazio, MD         
Sponsors and Collaborators
Massimo Imazio
  More Information

No publications provided

Responsible Party: Massimo Imazio, Cardiology Dpt ASLTO2, Maria Vittoria Hospital
ClinicalTrials.gov Identifier: NCT02219828     History of Changes
Other Study ID Numbers: 40/08/13, 2013-001849-13
Study First Received: August 14, 2014
Last Updated: August 17, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by Maria Vittoria Hospital:
pericarditis
recurrent pericarditis
corticosteroids
anakinra

Additional relevant MeSH terms:
Pericarditis
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 16, 2014