<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02219828</url>
  </required_header>
  <id_info>
    <org_study_id>40/08/13</org_study_id>
    <secondary_id>2013-001849-13</secondary_id>
    <nct_id>NCT02219828</nct_id>
  </id_info>
  <brief_title>AnakInRa for Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP)</brief_title>
  <acronym>AIR TRIP</acronym>
  <official_title>AnakInRa for Treatment of Recurrent Idiopathic Pericarditis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massimo Imazio</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maria Vittoria Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recent findings suggest that recurrent pericarditis (RP) may be a previously unrecognized&#xD;
      autoinflammatory disease. The pivotal pathogenic role of interleukin (IL)-1 in RP has been&#xD;
      shown by the achievement of complete responses after treatment with the recombinant&#xD;
      IL-1-receptor antagonist, anakinra. Anakinra is the recombinant form of IL-1Ra. The proposed&#xD;
      study is designed to demonstarate the efficacy of anakinra in RP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 8-month, multicenter (3 Italian centers), randomized, double-blind,&#xD;
      placebo-controlled, multicenter, medication-withdrawal study to evaluate the efficacy,&#xD;
      tolerability, and safety of anakinra in adults and children with idiopathic recurrent&#xD;
      pericarditis (RP).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recurrence rate</measure>
    <time_frame>8 months</time_frame>
    <description>Time to flare in the anakinra and placebo arms</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>1. responder status in the open label phase</measure>
    <time_frame>60 days</time_frame>
    <description>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:&#xD;
no or mild pericardial pain (a score ≤2.5 on a 21 circle VAS), AND&#xD;
normal CRP levels (CRP ≤0.5 mg/dL), AND&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2. change over time of the 3 outcome criteria, i.e. pericardial pain, CRP levels, and echocardiographic effusion;</measure>
    <time_frame>8 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3. time to response in the open label phase</measure>
    <time_frame>8 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>4. percentage of patients who relapse in the withdrawal part in the two arms;</measure>
    <time_frame>8 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5. change over time in patient's/parent's global assessment of overall well being on a 21 circle VAS;</measure>
    <time_frame>8 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6. change over time in the global evaluation of disease activity by physicians on a 21 circle VAS</measure>
    <time_frame>8 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>8. percentage off CS and any other concurrent medication at 6weeks</measure>
    <time_frame>6 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>9. tolerability and safety of the treatment</measure>
    <time_frame>8 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Idiopathic Recurrent Pericarditis</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo sc</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anakinra</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Anakinra 2mg/Kg up to 100mg (maximum dose)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anakinra</intervention_name>
    <description>2mg/Kg daily sc up to 100mgday as maximum dose</description>
    <arm_group_label>Anakinra</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient's written informed consent for ≥ 18 years of age before any assessment is&#xD;
             performed. Parents' or legal guardian's written informed consent and child's assent,&#xD;
             if appropriate, are required before any assessment is performed for patients &lt; 18&#xD;
             years of age.&#xD;
&#xD;
          2. Age &gt; 2 years and &lt;70 years at screening visit;&#xD;
&#xD;
          3. Recurrent pericarditis defined as a first episode of acute pericarditis followed by&#xD;
             recurrences (Ann Intern Med. 2011;155:409-14) (at least two recurrences for this&#xD;
             study). First episode of pericarditis is diagnosed when at least two of the following&#xD;
             criteria were present: pericarditic typical chest pain (sharp and pleuritic, improved&#xD;
             by sitting up and leaning forward), pericardial friction rubs, widespread ST segment&#xD;
             elevation or PR depressions not previously reported, and new or worsening pericardial&#xD;
             effusion. Recurrence is diagnosed when chest pain recurs and one or more of the&#xD;
             following signs is present: fever, pericardial friction rub, ECG changes,&#xD;
             echocardiographic evidence of new or worsening pericardial effusion, and elevations in&#xD;
             the white blood cell count, erythrocyte sedimentation rate or C-reactive protein. To&#xD;
             be enrolled in this study, elevation of C-reactive protein is mandatory both in the&#xD;
             first attack and in the following recurrences. We differentiate recurrences from&#xD;
             incessant pericarditis, term used to define patients with continued activity of&#xD;
             pericarditis (with a symptom-free interval of &lt; 6 weeks) (Soler-Soler J,&#xD;
             Sagristà-Sauleda J, Permanyer-Miralda G. Relapsing pericarditis. Heart.&#xD;
             2004;90:1364-8).&#xD;
&#xD;
          4. Specific etiologies excluded, including tuberculous, neoplastic or purulent&#xD;
             etiologies, post-cardiac injury syndromes, and rheumatic autoimmune diseases.&#xD;
&#xD;
          5. Records to document the number of prior pericardial recurrences, the time interval&#xD;
             between them as well as prior treatments must be made available from the medical&#xD;
             charts.&#xD;
&#xD;
          6. Troponin values during at least one previous attack is recorded.&#xD;
&#xD;
          7. QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative (PPD) test&#xD;
             has been previously made and recorded.&#xD;
&#xD;
          8. Patients will be enrolled at the time of a recurrent episode (at least the second&#xD;
             recurrence, i.e. third episode) or &quot;relapse&quot; of pericarditis documented by the&#xD;
             following criteria:&#xD;
&#xD;
               -  recurrent pericardial pain (with a score of least 5 on the 21 circles VAS) AND&#xD;
&#xD;
               -  increase in CRP≥1 mg/dL (being normal value = 0 - 0.5 mg/dL ), AND&#xD;
&#xD;
               -  one or more of the following signs: fever (≥ 37°C), pericardial friction rub,&#xD;
                  pertinent ECG changes, echocardiographic evidence of of new or worsening&#xD;
                  pericardial effusion (see definition above)&#xD;
&#xD;
          9. Continuous treatment with CS, the dose of which must not have been increased in the&#xD;
             three days preceding enrolment&#xD;
&#xD;
         10. Women of child bearing potentials (WCBP), defined as pre-menarche females aged 8 years&#xD;
             and above or all women physiologically capable of becoming pregnant, sexually active,&#xD;
             must use an effective form of contraception. Medically approved contraception (i.e.&#xD;
             one that results in a less than 1% per year failure rate when used consistently and&#xD;
             correctly, such as implants, injectables, combined oral contraceptives, and some&#xD;
             intrauterine devices) could include total abstinence. Reliable contraception should be&#xD;
             maintained throughout the study and for 3 months after anakinra discontinuation. Women&#xD;
             are considered post-menopausal and not WCBP if they have had 12 months of natural&#xD;
             (spontaneous) amenorrhea with an appropriate clinical profile (e.g. appropriate age,&#xD;
             history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH&#xD;
             levels &gt; 40 mIU/mL or have had surgical bilateral oophorectomy (with or without&#xD;
             hysterectomy) at least six weeks prior to study entry. In the case of oophorectomy&#xD;
             alone, only when the reproductive status of the woman has been confirmed by follow up&#xD;
             hormone level assessment she considered a WCBP.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients fulfilling any of the following criteria are not eligible for enrollment in&#xD;
             this study:&#xD;
&#xD;
               1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of&#xD;
                  a female after conception and until the termination of gestation, confirmed by a&#xD;
                  positive hCG laboratory test (&gt; 5 mIU/mL).&#xD;
&#xD;
               2. History of being immunocompromised, including a positive HIV at screening (ELISA&#xD;
                  and Western blot) test result.&#xD;
&#xD;
               3. Positive QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein&#xD;
                  Derivative (PPD) test (≥ 5 mm induration) performed after the first attack of&#xD;
                  pericarditis. Patients with a positive PPD test (≥ 5 mm induration) at screening&#xD;
                  may be enrolled only if they have either a negative chest X-ray or a negative&#xD;
                  QuantiFERON test.&#xD;
&#xD;
               4. Live vaccinations within three months prior to the start of the trial, during the&#xD;
                  trial, and up to three months following the last anakinra dose.&#xD;
&#xD;
               5. History of malignancy of any organ system (other than localized basal cell&#xD;
                  carcinoma of the skin), treated or untreated, within the past 5 years, regardless&#xD;
                  of whether there is evidence of local recurrence or metastases&#xD;
&#xD;
               6. History of significant other medical conditions, which in the Investigator's&#xD;
                  opinion would exclude the patient from participating in this trial including&#xD;
                  current pericarditis due to known diseases (e.g. tuberculosis, neoplastic or&#xD;
                  purulent causes, connective tissue diseases, acute rheumatic fever, etc.)&#xD;
&#xD;
               7. History of recurrent and/or evidence of active bacterial, fungal, or viral&#xD;
                  infection(s).&#xD;
&#xD;
               8. History of Type I hypersensitivity to anakinra.&#xD;
&#xD;
               9. History of poor compliance.&#xD;
&#xD;
              10. Use of any investigational drug (or biologic), or device within five half-lives&#xD;
                  of the drug prior to study entry or during the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Internal Medicine Division, OSpedale Papa Giovanni XXIII</name>
      <address>
        <city>Bergamo</city>
        <zip>24100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pediatric Dept. Ospedale Gaslini</name>
      <address>
        <city>Genova</city>
        <zip>16100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardiology Dpt, Maria Vittoria Hospital</name>
      <address>
        <city>Torino</city>
        <zip>10141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 19, 2014</study_first_posted>
  <last_update_submitted>December 17, 2015</last_update_submitted>
  <last_update_submitted_qc>December 17, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 18, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Maria Vittoria Hospital</investigator_affiliation>
    <investigator_full_name>Massimo Imazio</investigator_full_name>
    <investigator_title>Cardiology Dpt ASLTO2</investigator_title>
  </responsible_party>
  <keyword>pericarditis</keyword>
  <keyword>recurrent pericarditis</keyword>
  <keyword>corticosteroids</keyword>
  <keyword>anakinra</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pericarditis</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interleukin 1 Receptor Antagonist Protein</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02219828
org study id: 40/08/13
secondary id: 2013-001849-13
nct id: NCT02219828
lead sponsor: 
has dmc: Yes
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Recurrence rate
time frame: 8 months
description: Time to flare in the anakinra and placebo arms
measure: 1. responder status in the open label phase
time frame: 60 days
description: 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:
no or mild pericardial pain (a score ≤2.5 on a 21 circle VAS), AND
normal CRP levels (CRP ≤0.5 mg/dL), AND
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.
measure: 2. change over time of the 3 outcome criteria, i.e. pericardial pain, CRP levels, and echocardiographic effusion;
time frame: 8 months
description: 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.
measure: 3. time to response in the open label phase
time frame: 8 months
description: 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.
measure: 4. percentage of patients who relapse in the withdrawal part in the two arms;
time frame: 8 months
description: 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.
measure: 5. change over time in patient's/parent's global assessment of overall well being on a 21 circle VAS;
time frame: 8 months
description: 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.
measure: 6. change over time in the global evaluation of disease activity by physicians on a 21 circle VAS
time frame: 8 months
description: 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.
measure: 8. percentage off CS and any other concurrent medication at 6weeks
time frame: 6 weeks
description: 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.
measure: 9. tolerability and safety of the treatment
time frame: 8 months
description: 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: placebo sc
arm group label: Anakinra
arm group type: Active Comparator
description: Anakinra 2mg/Kg up to 100mg (maximum dose)
intervention type: Drug
intervention name: Anakinra
description: 2mg/Kg daily sc up to 100mgday as maximum dose
arm group label: Anakinra
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 5 Years
maximum age: 90 Years
healthy volunteers: No
facility: 
facility: 
facility: 
country: Italy
responsible party type: Sponsor-Investigator
investigator affiliation: Maria Vittoria Hospital
investigator full name: Massimo Imazio
investigator title: Cardiology Dpt ASLTO2
mesh term: Pericarditis
mesh term: Recurrence
mesh term: Interleukin 1 Receptor Antagonist Protein