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Trial record 74 of 75 for:    "Collagen Disease" | "Triamcinolone"

STep-up and Step-down Therapeutic Strategies in Childhood ARthritiS (STARS)

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ClinicalTrials.gov Identifier: NCT03728478
Recruitment Status : Recruiting
First Posted : November 2, 2018
Last Update Posted : August 12, 2019
Sponsor:
Collaborators:
Agenzia Italiana del Farmaco
Compagnia di San Paolo
Pfizer
Information provided by (Responsible Party):
Alessandro Consolaro, Istituto Giannina Gaslini

Brief Summary:
This study aims to compare the effectiveness of a conventional therapeutic regimen, based on treatment escalation (step-up strategy) and driven by the treat-to-target approach, with that of an early aggressive intervention based on the initial start of a combination of conventional and biological DMARDs (step-down strategy).

Condition or disease Intervention/treatment Phase
Oligoarthritis, Juvenile Polyarthritis, Juvenile, Rheumatoid Factor Negative Drug: Etanercept Drug: Methotrexate Drug: Intra-articular corticosteroid injections Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a a 12-month open label, randomised, actively controlled, multi-centre, prospective, superiority trial of two different treatment strategies (Step-down versus Step-up).

After signature of informed consent/assent patients will be randomized into two therapeutic arms: "Step-up" or "Step-down". Patients in the Step-up arm will be treated according to a conventional strategy based on treatment escalation and driven by the treat-to-target strategy. Patients in the Step-Down arm will be treated with an early, combined, aggressive therapy for 6 months.

After the conclusion of the 12-month observation period of the trial, patients will be followed for up to 5 years for the evaluation of disease course, medication requirements, adverse events, and long-term disease-related morbidity.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison of STep-up and Step-down Therapeutic Strategies in Childhood ARthritiS
Actual Study Start Date : May 29, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021


Arm Intervention/treatment
No Intervention: Treatment arm 1: Step-up
JIA patients managed with a Treat-To-Target strategy (T2T)
Experimental: Treatment arm 2: Step-down
JIA patients treated with an early combined therapy
Drug: Etanercept
Patients will receive etanercept subcutaneously at a dose of 0.8 mg/kg weekly (up to a maximum dose of 50 mg weekly).

Drug: Methotrexate
Methotrexate will be administered subcutaneously, in a single weekly dose of 15 mg/m2 (max 20 mg).

Drug: Intra-articular corticosteroid injections
Triamcinolone hexacetonide and methylprednisolone acetate doses depend on the affected joint.




Primary Outcome Measures :
  1. Clinical remission on or off medication at 12 months [ Time Frame: 12 months ]
    The effectiveness of the two therapeutic strategies will be compared by assessing the frequency of clinical remission (CR) at 12 months. CR is defined as the persistence of the JADAS state of ID for at least 6 months.


Secondary Outcome Measures :
  1. Inactive disease [ Time Frame: 12 months ]
    The rate of patients who achieve the JADAS/JIA ACR state of ID at any single point in time throughout the study period will be compared between the 2 arms.

  2. Time to inactive disease as per JADAS/JIA ACR criteria [ Time Frame: 12 months ]
    Time to achieve the state of JADAS/JIA ACR ID will be calculated as the time difference (in days) between the date of randomization and the date of the visit at which the patient will be observed to be in ID.

  3. Time to JADAS/JIA ACR clinical remission [ Time Frame: 12 months ]
    Time to achieve the state of JADAS/JIA ACR ID will be calculated as the time difference (in days) between the date of randomization and the date of the visit at which the patient will be observed to be in clinical remission (i.e. persistent inactive disease for at least 6 months).

  4. Time spent in JADAS/JIA ACR inactive disease [ Time Frame: 12 months ]
    The cumulative time spent in the JADAS/JIA ACR state of ID will be calculated as the time difference (in days) between the date of the first visit at which the patient will be observed to be in ID and the date at which he/she will be observed to be no longer in ID that is when the disease will flare (see later for definitions), or database closure for analysis purposes. We will assume that if a patient is found to be in ID at 2 consecutive visits, the patient had ID on all days between these visits. If a patient will be found to have ID at a particular visit, but lost the ID status at the subsequent visit, the patient will be considered to have been in ID until the recurrence of active disease. Patients found to be in ID only at the time of database closure will contribute a single day of ID. The time in inactive disease per patient will be recorded and compared between the 2 arms.

  5. Cumulative level of disease activity throughout the study period [ Time Frame: 12 months ]
    The area under the curve (AUC) of the JADAS10 score assessed at every study visit and the AUC of the parent version of the JADAS (parJADAS) assessed monthly will be recorded and compared between the 2 arms.

  6. Time spent on therapy [ Time Frame: 12 months ]
    The cumulative time on therapy will be calculated as the time difference (in days) between the date of the visit at which the patient will start a systemic medication (synthetic or biologic DMARDs or steroids) until the date at which he/she will be observed to no longer be in treatment with a systemic medication, or completed the study. We assume that if a patient does not receive medications at 2 consecutive visits, the patient had not received medications all days between these visits. Patients initiating a systemic treatment at the final visit of the study will contribute a single day of time in therapy. The mean percentage of time spent on therapy per patient will be recorded and compared between the 2 arms.

  7. Rate of flares [ Time Frame: 12 months ]
    The rate of patients who develop flare, defined as the recurrence of active disease after attaining inactive disease at last visit according JADAS or JIA ACR definition, and the number of flares and the time to flare per patient will be recorded and compared. Notably, all patients prescribed intra-articular injections, synthetic or biologic DMARDs or systemic steroids will be considered as flare independently from JADAS or ACR criteria.

  8. Rate of uveitis onset [ Time Frame: 12 months ]
    The rate of patients who develop uveitis according to the Standardized Uveitis Nomenclature (SUN) will be recorded and compared between the 2 arms. The rate of patients requiring systemic medications for treatment of uveitis will be also recorded and compared between the 2 arms. However, these patients will be excluded from the study and followed for safety only.



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Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Each patient must meet all the following criteria in order to be enrolled in the trial:

I. Newly-diagnosed and synthetic or biologic DMARD-naïve children (only treatment with 1 NSAID is allowed and no corticosteroid joint injections prior to randomization ) with a JIA classified according to the following ILAR categories:

i. Oligoarthritis ii. Rheumatoid factor negative polyarthritis

II. Active arthritis

III. Onset of JIA symptoms no more than 6 months before randomization

IV. Age 2 to 17 years at enrolment.

V. Female of child-bearing potential must have a negative pregnancy test at the beginning of the trial. If sexually active, they must agree to use highly effective contraceptive measures, throughout study participation, and must have no intention of conceiving during the course of the study. Post-pubertal males must have no plans to father a child during the study and agree to use highly effective contraceptive measures if sexually active.

VI. Ability to comply with the entire study procedures, ability to communicate meaningfully with the investigational staff, competence to give written informed consent; to be applied to the parents and/or patients, as appropriate

VII. Duly executed, written, informed consent/assent obtained from the parents/patient.

Exclusion criteria

I. Classification in one of the following JIA categories: systemic arthritis, RF-positive polyarthritis, psoriatic arthritis, enthesitis-related arthritis, undifferentiated arthritis

II. Patients who need systemic treatment for uveitis

III. Tuberculosis related issues: patients are excluded from the study if they have:

  1. Active TB or a history of incompletely treated TB
  2. PPD or QuantiFERON-TB positive patients (with no active disease) unless it is documented by a specialist that the patient has been adequately treated for TB and can start treatment with a biologic agent, based on the medical judgment of the study investigator and / or an infectious disease specialist.
  3. Suspected extrapulmonary TB infection
  4. Patients at high risk of contracting TB, such as close contact with individual with active or latent TB

IV. Previous treatment with any synthetic or biologic DMARD

V. Any live attenuated vaccine within 4 weeks prior to the baseline visit, such as varicella-zoster, oral polio, measles, mumps or rubella vaccines and throughout the study. Killed or inactive vaccine may be permitted based on the investigator's judgment

VI. Prior or current history of malignancy or any other significant concomitant illness(es) as per the treating physician evaluation

VII. Any of the following laboratory abnormalities based on the most recent laboratory results:

  1. White blood cell (WBC) count <3.50 x 103/mm3 (SI units: <3.50 x 109/L) and neutrophils < 1x109/L;
  2. Hemoglobin < 8.5 g/dL (SI units: <85 g/L);
  3. Platelet Count < 125,0000/mm3 or ≥1,000,000/mm3 (SI units: <125 x 109/L or ≥1,000 x 109/L
  4. Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) ≥ 2.0 x upper limit of normal (ULN).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03728478


Contacts
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Contact: Alessandro Consolaro, MD, PhD 01056362729 alessandroconsolaro@gaslini.org
Contact: Marta Mazzoni, MD, 01056363576 martamazzoni87@yahoo.it

Locations
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Italy
IRCCS Istituto Giannina Gaslini Recruiting
Genova, GE, Italy, 16147
Contact: Alessandro Consolaro, MD    +39 01056362729    alessandroconsolaro@gaslini.org   
Sponsors and Collaborators
Istituto Giannina Gaslini
Agenzia Italiana del Farmaco
Compagnia di San Paolo
Pfizer

Publications:
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Responsible Party: Alessandro Consolaro, Principal Investigator, Istituto Giannina Gaslini
ClinicalTrials.gov Identifier: NCT03728478     History of Changes
Other Study ID Numbers: 2018-001931-27
First Posted: November 2, 2018    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Alessandro Consolaro, Istituto Giannina Gaslini:
juvenile idiopathic arthritis
treatment
treat to target

Additional relevant MeSH terms:
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Rheumatic Diseases
Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Etanercept
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents