Therapeutic Approach in Colchicine-resistant Recurrent pEricarditis in Children

NCT05805930 | Not Yet Recruiting Phase 3

• 1 other identifier: CREATE
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief 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 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.

Conditions

Pericarditis

Outcome Measures

Primary Outcomes (2)

• Number of participants with complete response to treatment

  Complete response to treatment at day 7

  Day 7

• Number of participants with disease Flare

  Absence of flare after 3 months of therapy

  3 months

Secondary Outcomes (2)

• Time to response

  Up to 24 weeks

• Number of participants with improved Quality of life

  Up to 24 weeks

Study Arms (2)

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).

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.

Drug: Anakinra

Interventions

Anakinra DRUG

: 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.

Arm 2: Anakinra

Prednisone DRUG

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.

Also known as: Steroid, Corticosteroid

Arm 1: Steroids

Eligibility Criteria

• Age: 8 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Istituto Giannina Gaslini: lead

MeSH Terms

Conditions

Pericarditis

Interventions

Interleukin 1 Receptor Antagonist Protein; Prednisone; Steroids; Adrenal Cortex Hormones

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; Pregnadienediols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Roberta Caorsi, MD

CONTACT

+39 010 56362916; robertacaorsi@gaslini.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Trial Centre

Study Record Dates

• First Submitted: March 23, 2023
• First Posted: April 10, 2023
• Study Start: June 1, 2023
• Primary Completion: June 1, 2025
• Study Completion (Estimated): May 31, 2026
• Last Updated: April 10, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share