PericarditisPhase 3CREATENCT05805930
Therapeutic Approach in Colchicine-resistant Recurrent pEricarditis in Children
A Phase 3 study testing Anakinra and Prednisone in people with Pericarditis, run by Istituto Giannina Gaslini.
Trial summary
The purpose of this study is to demonstrate that anakinra provides more rapid disease control than steroids in the first month of treatment in the event of recurrent pericarditis and is more effective in preventing further exacerbations in patients aged between eight months and eighteen years of age with idiopathic or… Read more about this study
- Who is it for?
- Ages 8 months to 18 years
- Conditions the study is for
- Pericarditis
- What is being tested?
- Anakinra and Prednisone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2023to 31 May 2026
- Phase
- Phase 3
- 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 8 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male and female patients.
- Parent or legal guardian written informed consent and child assent, if appropriate, are required before any assessment is performed.
- Diagnosis of relapse of pericarditis in a patient with previous diagnosis of acute pericarditis (idiopathic or secondary to invasive cardiac procedures).
- Inadequate response or intolerance to non-steroidal anti-inflammatory drugs or colchicine
Who cannot join
- Pericarditis secondary to a known infection (viral, bacterial, mycobacterial).
- Pericarditis in a patient with a previous diagnosis of any neoplasm and without complete recovery from at least one year.
- Pericarditis in the context of a systemic disease.
- Patients fulfilling diagnostic criteria for an autoimmune systemic disease
- Patients with a previous diagnosis of a genetically confirmed autoinflammatory disease
- Any conditions or significant medical problems, which in the opinion of the investigator places the patient at unacceptable risk for immunomodulatory therapy.
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- Main alteration in the blood count
- Presence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B or Hepatitis C infections.
- Evidence of active or latent tuberculosis (TB) determined by positive QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative (PPD) test (≥5 mm induration) within 2 months prior to randomization.
- Administration of any investigational drug or implantation of investigational device, or participation in another trial, within 30 days before screening.
- Use of steroids at the dosage of 1 mg/kg/day of prednisone or equivalent for at least 5 days in the 30 days before randomization.
- Live vaccinations within 1 months prior to the start of the trial and during the trial.
- Pregnancy, confirmed by a positive hCG laboratory test.
- Female adolescents (≤18 years of age) of childbearing potential who do not agree to abstinence or, if sexually active, do not agree to the use of contraception.
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Trial locations and contacts
No sites are listed yet.
About this study
Official title: Therapeutic Approach in Colchicine-resistant Recurrent pEricarditis in Children: an Open-label Randomized Trial Comparing Anakinra vs sTEroids
The purpose of this study is to demonstrate that anakinra provides more rapid disease control than steroids in the first month of treatment in the event of recurrent pericarditis and is more effective in preventing further exacerbations in patients aged between eight months and eighteen years of age with idiopathic or post-procedural pericarditis, unresponsive to first-line treatment with NSAIDs and colchicine at the appropriate dosage, or in case of colchicine intolerance. The efficacy of the two treatments will be evaluated by the capacity and timing of the two therapies to determine a complete control (clinical, laboratory and instrumental) of the disease and the absence of recurrences.
Read the detailed description
Although steroids represent the second-line treatment for recurrent pericarditis (RP), to be used in case of inadequate response to NSAIDs and colchicine, their use is controversial due to their side effects.
Indeed, in adult patients with RP it has been demonstrated that the use of steroids is associated with an increased risk of recurrence: in a study carried out in adult patients, 64% of patients taking high-dose steroids (> 1 mg/kg/ of prednisone or equivalent), and 32% of patients taking this low-dose drug (< 1 mg/kg/day of prednisone or equivalent) relapsed. Furthermore, the therapy is associated with serious side effects and an increased risk of hospitalization, especially in patients treated with high doses. Finally, a high percentage of RP patients (both adult and pediatric) treated with steroids tend to become steroid-dependent, experiencing a disease exacerbation during tapering of treatment or soon after its discontinuation. The side effects associated with the chronic use of steroids are well known, especially in childhood, as their use is associated not only with reduced bone density, but also with growth retardation. Therefore, their long-term use is contraindicated, especially in children.
In a recent retrospective study of 58 pediatric patients with recurrent pericarditis treated with IL-1 inhibitors, a high steroid dependence rate was observed (45 of 48 treated patients). In this study, the presence of predictive factors associated with the possibility of achieving long-term remission was evaluated. Unfortunately, it could not be shown that avoiding steroid use was associated with an increased chance of withdrawing anakinra without relapse. This is likely due to the large variability of the cohort included in the retrospective study.
Therapy with anakinra in recurrent pericarditis is aimed at obtaining rapid and complete control of the disease and maintaining it over time, allowing the suspension of steroid therapy and thus reducing the risk of complications, chronicity and recurrence.
In the field of pediatric rheumatology, there is convincing evidence that in children with chronic arthritis a more aggressive therapy at an early stage can take advantage of the so-called "window of opportunity": according to this theory, early biological treatment can modify the pathogenetic mechanism of the disease by improving its long-term outcomes.
In particular, it has been shown that anakinra therapy in children with systemic JIA can lead to rapid attainment of inactive disease and allow for early discontinuation of treatment in the absence of recurrence in the majority of patients. Among all the rheumatological pathologies of the pediatric age, systemic JIA is the one that has the greatest similarities with autoinflammatory diseases due to the presence of fever, sometimes recurrent, rash and serositis, typical characteristics of AID, especially of inflammasomopathies. Recurrent pericarditis itself has many similarities to these conditions, as demonstrated by the efficacy of interleukin-1 inhibition. In fact, both of these conditions are considered by many to be real autoinflammatory diseases, with a multifactorial etiology. It is therefore reasonable to think that the concept of the "window of opportunity" can also be translated to recurrent pericarditis: the early blockade of cytokines could in fact abrogate the pathogenetic mechanism of the disease and therefore its chronic course and/or its relapses.
- Conditions
- Pericarditis
- Being tested
- Anakinra, Prednisone
- Medical subject headings
- Pericarditis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnakinraDrug
: Patients will continue daily treatment with anakinra up to week 12. Treatment will be then progressively tapered through the reduction of an administration of the drug per week. Reductions will be performed every 2 weeks up to discontinuation. Therefore, if a relapse does not occur, the treatment will be withdrawn at week 24.
PrednisoneDrug
Also called Steroid, Corticosteroid
Steroids will be progressively tapered with a reduction of 0,1-0,15 mg/kg/day of prednisone (or 5 mg in patients in treatment with the maximum dosage of 50 mg/day) from the ongoing treatment every week up to discontinuation. If a relapse does not occur, the treatment will be withdrawn in a period of time of 10 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Steroids | Active comparator | Treatment with prednisone will be initiated at a dosage of 1 mg/kg/day (maximum 50 mg/day) in twice daily administration for 14 days. In case of complete response to treatment, prednisone will be reduced from day 14, otherwise it will be continued at 1 mg/kg/day until day 28 (week 4). Patients with complete response at day 28 will continue the study entering part 2, in which therapy will be progressively tapered.
In part 2, prednisone will be tapered progressively by 0.1-0.15 mg/kg/day of prednisone (or 5 mg in patients on the maximum dose of 50 mg/day) from current treatment every week until the break. If there is no relapse, treatment will be discontinued over a 10-week period. Patients will then be evaluated every 4 weeks until the end of the study (week 24). Receives: Drug: Prednisone |
| Arm 2: Anakinra | Experimental | Treatment with anakinra will be initiated at a dose of 2 mg/kg/day (maximum dose 100 mg/day) as a single daily dose and maintained until day 28 (week 4).
Patients who achieve a complete treatment response at week 4 (day 28) will continue the study into Part 2. Patients without a complete treatment response will drop out of the study.
In Part 2 patients will continue daily anakinra treatment through week 12. The treatment will then be progressively reduced through the reduction of one weekly administration of the drug. The reductions will be made every 2 weeks until the interruption. Therefore, if no relapse occurs, treatment will be discontinued at week 24. Receives: Drug: Anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with complete response to treatment
Complete response to treatment at day 7
Measured: Day 7
Number of participants with disease Flare
Absence of flare after 3 months of therapy
Measured: 3 months
Secondary outcomes (2)
Time to response
Time to respond to treatment
Measured: Up to 24 weeks
Number of participants with improved Quality of life
Evaluation of quality of life through specific questionnaire
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2023
- Study start1 Jun 2023 (estimated)
- Primary completion1 Jun 2025 (estimated)
- Study completion31 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Giannina Gaslini
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicolino Ruperto, MD, MPH, Istituto Giannina Gaslini
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05805930
- Sponsor's protocol ID
- CREATE
- Acronym
- CREATE
- Status last verified
- Apr 2023
- First submitted
- 23 Mar 2023
- Last updated
- 10 Apr 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Approach in Colchicine-resistant Recurrent pEricarditis in Children: an Open-label Randomized Trial Comparing Anakinra vs sTEroids
- ClinicalTrials.gov ID
- NCT05805930
- Acronym / sponsor ID
- CREATE / CREATE
- Conditions
- Pericarditis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Istituto Giannina GasliniUniversity, hospital or other
- Study start
- 1 Jun 2023 (estimated)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 31 May 2026 (estimated)
- First posted
- 10 Apr 2023 (actual)
- 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.
The purpose of this study is to demonstrate that anakinra provides more rapid disease control than steroids in the first month of treatment in the event of recurrent pericarditis and is more effective in preventing further exacerbations in patients aged between eight months and eighteen years of age with idiopathic or post-procedural pericarditis, unresponsive to first-line treatment with NSAIDs and colchicine at the appropriate dosage, or in case of colchicine intolerance. The efficacy of the two treatments will be evaluated by the capacity and timing of the two therapies to determine a complete control (clinical, laboratory and instrumental) of the disease and the absence of recurrences.
Detailed description
Although steroids represent the second-line treatment for recurrent pericarditis (RP), to be used in case of inadequate response to NSAIDs and colchicine, their use is controversial due to their side effects.
Indeed, in adult patients with RP it has been demonstrated that the use of steroids is associated with an increased risk of recurrence: in a study carried out in adult patients, 64% of patients taking high-dose steroids (> 1 mg/kg/ of prednisone or equivalent), and 32% of patients taking this low-dose drug (< 1 mg/kg/day of prednisone or equivalent) relapsed. Furthermore, the therapy is associated with serious side effects and an increased risk of hospitalization, especially in patients treated with high doses. Finally, a high percentage of RP patients (both adult and pediatric) treated with steroids tend to become steroid-dependent, experiencing a disease exacerbation during tapering of treatment or soon after its discontinuation. The side effects associated with the chronic use of steroids are well known, especially in childhood, as their use is associated not only with reduced bone density, but also with growth retardation. Therefore, their long-term use is contraindicated, especially in children.
In a recent retrospective study of 58 pediatric patients with recurrent pericarditis treated with IL-1 inhibitors, a high steroid dependence rate was observed (45 of 48 treated patients). In this study, the presence of predictive factors associated with the possibility of achieving long-term remission was evaluated. Unfortunately, it could not be shown that avoiding steroid use was associated with an increased chance of withdrawing anakinra without relapse. This is likely due to the large variability of the cohort included in the retrospective study.
Therapy with anakinra in recurrent pericarditis is aimed at obtaining rapid and complete control of the disease and maintaining it over time, allowing the suspension of steroid therapy and thus reducing the risk of complications, chronicity and recurrence.
In the field of pediatric rheumatology, there is convincing evidence that in children with chronic arthritis a more aggressive therapy at an early stage can take advantage of the so-called "window of opportunity": according to this theory, early biological treatment can modify the pathogenetic mechanism of the disease by improving its long-term outcomes.
In particular, it has been shown that anakinra therapy in children with systemic JIA can lead to rapid attainment of inactive disease and allow for early discontinuation of treatment in the absence of recurrence in the majority of patients. Among all the rheumatological pathologies of the pediatric age, systemic JIA is the one that has the greatest similarities with autoinflammatory diseases due to the presence of fever, sometimes recurrent, rash and serositis, typical characteristics of AID, especially of inflammasomopathies. Recurrent pericarditis itself has many similarities to these conditions, as demonstrated by the efficacy of interleukin-1 inhibition. In fact, both of these conditions are considered by many to be real autoinflammatory diseases, with a multifactorial etiology. It is therefore reasonable to think that the concept of the "window of opportunity" can also be translated to recurrent pericarditis: the early blockade of cytokines could in fact abrogate the pathogenetic mechanism of the disease and therefore its chronic course and/or its relapses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Steroids | Active comparator | Drug: PrednisoneTreatment with prednisone will be initiated at a dosage of 1 mg/kg/day (maximum 50 mg/day) in twice daily administration for 14 days. In case of complete response to treatment, prednisone will be reduced from day 14, otherwise it will be continued at 1 mg/kg/day until day 28 (week 4). Patients with complete response at day 28 will continue the study entering part 2, in which therapy will be progressively tapered. In part 2, prednisone will be tapered progressively by 0.1-0.15 mg/kg/day of prednisone (or 5 mg in patients on the maximum dose of 50 mg/day) from current treatment every week until the break. If there is no relapse, treatment will be discontinued over a 10-week period. Patients will then be evaluated every 4 weeks until the end of the study (week 24). |
| Arm 2: Anakinra | Experimental | Drug: AnakinraTreatment with anakinra will be initiated at a dose of 2 mg/kg/day (maximum dose 100 mg/day) as a single daily dose and maintained until day 28 (week 4). Patients who achieve a complete treatment response at week 4 (day 28) will continue the study into Part 2. Patients without a complete treatment response will drop out of the study. In Part 2 patients will continue daily anakinra treatment through week 12. The treatment will then be progressively reduced through the reduction of one weekly administration of the drug. The reductions will be made every 2 weeks until the interruption. Therefore, if no relapse occurs, treatment will be discontinued at week 24. |
Who may qualify
- Ages
- 8 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Male and female patients.
- Parent or legal guardian written informed consent and child assent, if appropriate, are required before any assessment is performed.
- Diagnosis of relapse of pericarditis in a patient with previous diagnosis of acute pericarditis (idiopathic or secondary to invasive cardiac procedures).
- Inadequate response or intolerance to non-steroidal anti-inflammatory drugs or colchicine
Key exclusion criteria (15 listed)
- Pericarditis secondary to a known infection (viral, bacterial, mycobacterial).
- Pericarditis in a patient with a previous diagnosis of any neoplasm and without complete recovery from at least one year.
- Pericarditis in the context of a systemic disease.
- Any conditions or significant medical problems, which in the opinion of the investigator places the patient at unacceptable risk for immunomodulatory therapy.
- Main alteration in the blood count
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 |
|---|---|---|
| Anakinra: Patients will continue daily treatment with anakinra up to week 12. Treatment will be then progressively tapered through the reduction of an administration of the drug per week. Reductions will be performed every 2 weeks up to discontinuation. Therefore, if a relapse does not occur, the treatment will be withdrawn at week 24. | Drug | Arm 2: Anakinra |
| PrednisoneAlso: Steroid, CorticosteroidSteroids will be progressively tapered with a reduction of 0,1-0,15 mg/kg/day of prednisone (or 5 mg in patients in treatment with the maximum dosage of 50 mg/day) from the ongoing treatment every week up to discontinuation. If a relapse does not occur, the treatment will be withdrawn in a period of time of 10 weeks. | Drug | Arm 1: Steroids |
Primary outcome
Number of participants with complete response to treatment
Time frame: Day 7
Complete response to treatment at day 7
Number of participants with disease Flare
Time frame: 3 months
Absence of flare after 3 months of therapy
2 secondary outcomes
Time to response
Time frame: Up to 24 weeks
Number of participants with improved Quality of life
Time frame: Up to 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2023.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Anakinra and Prednisone in people with Pericarditis, run by Istituto Giannina Gaslini.
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 4 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 10 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Roberta Caorsi, MD (+39 010 56362916, robertacaorsi@gaslini.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with complete response to treatment (time frame: Day 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Apr 2023.