Idiopathic Recurrent PericarditisPhase 4AIR TRIPNCT02219828
AnakInRa for Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP)
A Phase 4 study testing Anakinra in people with Idiopathic Recurrent Pericarditis, run by Massimo Imazio at 3 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 90 years
- Conditions the study is for
- Idiopathic Recurrent Pericarditis
- What is being tested?
- Anakinra
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 3 sitesItaly
- Study dates
- Jun 2014to Oct 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 90 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
3 sites in 1 country.
Italy3 sites
Internal Medicine Division, OSpedale Papa Giovanni XXIII
Bergamo, Bergamo, 24100
Pediatric Dept. Ospedale Gaslini
Genova, Genova, 16100
Cardiology Dpt, Maria Vittoria Hospital
Torino, Torino, 10141
About this study
Official title: AnakInRa for Treatment of Recurrent Idiopathic Pericarditis
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.
Read the 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).
- Conditions
- Idiopathic Recurrent Pericarditis
- Being tested
- Anakinra, Placebo
- Keywords
- pericarditis, recurrent pericarditis, corticosteroids, anakinra
- Medical subject headings
- Pericarditis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnakinraDrug
2mg/Kg daily sc up to 100mgday as maximum dose
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | placebo sc Receives: Drug: Placebo |
| Anakinra | Active comparator | Anakinra 2mg/Kg up to 100mg (maximum dose) Receives: Drug: Anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence rate
Time to flare in the anakinra and placebo arms
Measured: 8 months
Secondary outcomes (8)
1. responder status in the open label phase
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.
Measured: 60 days
2. change over time of the 3 outcome criteria, i.e. pericardial pain, CRP levels, and 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.
Measured: 8 months
3. time to response in the open label phase
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.
Measured: 8 months
4. percentage of patients who relapse in the withdrawal part in the two arms;
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.
Measured: 8 months
5. change over time in patient's/parent's global assessment of overall well being on a 21 circle VAS;
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.
Measured: 8 months
6. change over time in the global evaluation of disease activity by physicians on a 21 circle VAS
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.
Measured: 8 months
8. percentage off CS and any other concurrent medication at 6weeks
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.
Measured: 6 weeks
9. tolerability and safety of the treatment
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.
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2014 (estimated)
- Study startJun 2014
- Primary completionJul 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Recurrent PericarditisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massimo Imazio
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Massimo Imazio, Maria Vittoria Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02219828
- Sponsor's protocol ID
- 40/08/13
- Other IDs
- 2013-001849-13
- Acronym
- AIR TRIP
- Status last verified
- Dec 2015
- First submitted
- 14 Aug 2014
- Last updated
- 18 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 27825009
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AnakInRa for Treatment of Recurrent Idiopathic Pericarditis
- ClinicalTrials.gov ID
- NCT02219828
- Acronym / sponsor ID
- AIR TRIP / 40/08/13
- Conditions
- Idiopathic Recurrent Pericarditis
- Keywords
- pericarditis, recurrent pericarditis, corticosteroids, anakinra
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Massimo ImazioUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Jul 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 19 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placeboplacebo sc |
| Anakinra | Active comparator | Drug: AnakinraAnakinra 2mg/Kg up to 100mg (maximum dose) |
Who may qualify
- Ages
- 5 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (11 listed)
- Patients fulfilling any of the following criteria are not eligible for enrollment in this study:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anakinra2mg/Kg daily sc up to 100mgday as maximum dose | Drug | Anakinra |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Recurrence rate
Time frame: 8 months
Time to flare in the anakinra and placebo arms
8 secondary outcomes
1. responder status in the open label phase
Time frame: 60 days
2. change over time of the 3 outcome criteria, i.e. pericardial pain, CRP levels, and echocardiographic effusion;
Time frame: 8 months
3. time to response in the open label phase
Time frame: 8 months
4. percentage of patients who relapse in the withdrawal part in the two arms;
Time frame: 8 months
5. change over time in patient's/parent's global assessment of overall well being on a 21 circle VAS;
Time frame: 8 months
6. change over time in the global evaluation of disease activity by physicians on a 21 circle VAS
Time frame: 8 months
8. percentage off CS and any other concurrent medication at 6weeks
Time frame: 6 weeks
9. tolerability and safety of the treatment
Time frame: 8 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2015.
- Derived from this study: PubMed 27825009Brucato 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Anakinra in people with Idiopathic Recurrent Pericarditis, run by Massimo Imazio at 3 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence rate (time frame: 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02219828, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2015.