Plain English Summary
Background and study aims
The aim of this study is to compare two different steroid treatments in children and young people with new-onset polyarticular juvenile idiopathic arthritis (JIA) to find out which is best. Medications used in the long-term management of JIA take around 12 weeks to start working. Steroids act quickly, reducing inflammation whilst the other medications start to work but have many potential side effects. There is a lack of evidence to suggest whether intravenous steroids or oral steroids are more effective, safe, tolerable for patients and which have a greater impact on quality of life.
Who can participate?
Patients aged 1-18 years of age with at least five inflamed joints and newly diagnosed polyarticular JIA
What does the study involve?
They will be randomly allocated to either a 6-week course (reducing dose regimen) of prednisolone liquid or tablets, taken at home OR a 3-day course of intravenous methylprednisolone on a hospital day-case unit. Participants will be assessed before starting treatment (baseline) and four follow-up visits at 6, 12, 24 and 52 weeks, in line with standard care appointments. Study visits will include assessments in standard care however, additional study-specific assessments will include reporting of side effects, and steroid toxicity risk including extra blood tests, questionnaires relating to the impact of JIA and treatment on quality of life and cost. The study offers an option for participants to donate blood samples for storage in a biobank for future research. Samples will not be analysed as part of the study but adopted by Liverpool University Biobank.
What are the possible benefits and risks of participating?
The direct burden on participation will be minimal as all research visits have been scheduled at the same time as standard-of-care visits to minimise the burden to participants. Research blood samples are taken at the same time as standard-of-care bloods to reduce burden.
Participants will be asked to complete several questionnaires which will prolong their clinic appointments. Once complete the questionnaire will be handed to the research team.
Risks associated with being treated with steroids (the IMP and the comparator) via different routes for JIA with the IMP, These risks are stated in the trial information sheets and site teams are appropriately trained as both routes of administration are used as standard of care.
All of the above risks are minimized with appropriate training and following policies and procedures by hospital Trusts and as stated in the protocol. For participants receiving oral prednisolone from hospital pharmacies, the pharmacy will dispense the drug as prescribed with appropriate guidance for taking it. For participants receiving IV methylprednisolone over 3 days on a hospital day unit, nurses who normally work on the day unit and have been appropriately trained to give IV methylprednisolone will be responsible for administering the drug and monitoring participants. It will not be given by Research Nurses who may be less familiar with the administration of this drug and do not usually administer this drug. This will minimize the risk of drug preparation, administration and monitoring errors.
Where is the study run from?
Alder Hey Children's NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
July 2023 to December 2026
Who is funding the study?
Health Technology Assessment Programme (UK)
Who is the main contact?
star-jia@liverpool.ac.uk
Study website
Contact information
Type
Scientific
Contact name
Dr Alison Hudak
ORCID ID
Contact details
Liverpool Clinical Trials Centre
Block C
Waterhouse Building
Brownlow Street
Liverpool
L69 3GL
United Kingdom
+44 (0)151 7940619
star-jia@liverpool.ac.uk
Type
Public
Contact name
Dr Alison Hudak
ORCID ID
Contact details
Liverpool Clinical Trials Centre
Block C
Waterhouse Building
Brownlow Street
Liverpool
L69 3GL
United Kingdom
+44 (0)151 7940619
star-jia@liverpool.ac.uk
Type
Principal Investigator
Contact name
Dr Clare Pain
ORCID ID
Contact details
Eaton Road
Liverpool
L12 2AP
United Kingdom
+44 (0)151 2284811
Clare.Pain@alderhey.nhs.uk
Additional identifiers
EudraCT/CTIS number
Nil known
IRAS number
1007610
ClinicalTrials.gov number
Nil known
Protocol/serial number
AH23-05-006, IRAS 1007610, CPMS 58347
Study information
Scientific title
Steroid Treatment Trial in JIA (STAR-JIA): A randomised trial to compare the effectiveness, safety and cost-effectiveness of intravenous versus oral corticosteroid induction regimens for children and young people with juvenile idiopathic arthritis
Acronym
STAR-JIA
Study hypothesis
Primary objectives:
To compare the clinical effectiveness of intravenous methylprednisolone versus oral prednisolone for controlling new-onset polyarticular juvenile idiopathic arthritis (JIA) in JIA Core Outcomes.
Secondary objectives:
1. To compare the differences in JIA Core Outcomes for intravenous methylprednisolone versus oral prednisolone for the following domains:
1.1. Pain
1.2. Function
1.3. Health-related Quality of Life (HRQOL)
2. To assess the effectiveness of intravenous versus oral corticosteroids in minimising the need for additional treatments including all corticosteroid routes and additional disease-modifying anti-rheumatic drugs (DMARDs)/biologics.
3. To evaluate short/medium-term safety and tolerability of IV versus oral corticosteroids, with regards to adverse reactions, serious adverse events, laboratory assessments and paediatric glucocorticoid toxicity index (pGTI).
4. To determine if a dose-response relationship can be identified in the efficacy/adverse responses to corticosteroids across all participants by secondary analysis, normalising corticosteroids received for dose, bioavailability and potency using previously published data.
Ethics approval(s)
Approved 08/09/2023, Yorkshire and the Humber - Leeds East (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle-upon-Tyne, NE2 4NQ, United Kingdom; +44 (0)207 1048171, (0)207 104 8141; leedseast.rec@hra.nhs.uk), ref: 23/YH/0173
Study design
Open randomized controlled parallel-group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment, Safety, Efficacy
Patient information sheet
Not available in web format, please use the contact details to request a participant information sheet
Condition
Juvenile idiopathic arthritis (polyarticular)
Intervention
IMP: Intravenous methylprednisolone administered over 3 days on a hospital day unit
Comparator: Oral prednisolone taken/administered over 6 weeks at home
The doses, frequency and method of administration of the IMP and comparator drug are provided below.
IMP: Methylprednisolone
Route: Intravenous administration
Form: Powder for injection to be prepared for intravenous administration
30 mg/kg per day for 3 consecutive days (Maximum dose: 1g per day)
Comparator: Prednisolone
Route: Oral administration
Form: Tablet or solution
The initial dose of prednisolone will be 1 mg/kg per day with a maximum dose of 40 mg. For participants weighing ≥40 kg, the weaning will be a reduction in line with the percentage decrease used for lighter patients.
Week of oral prednisolone 1: Dose (patient <40 kg): 1 mg/kg per day; Dose (patient ≥40 kg): 40 mg
Week of oral prednisolone 2: Dose (patient <40 kg): 0.75 mg/kg per day; Dose (patient ≥40 kg): 30 mg
Week of oral prednisolone 3: Dose (patient <40 kg): 0.5 mg/kg per day; Dose (patient ≥40 kg): 20 mg
Week of oral prednisolone 4: Dose (patient <40 kg): 0.375 mg/kg per day; Dose (patient ≥40 kg): 15 mg
Week of oral prednisolone 5: Dose (patient <40 kg): 0.25 mg/kg per day; Dose (patient ≥40 kg): 10 mg
Week of oral prednisolone 6: Dose (patient <40 kg): 0.125 mg/kg per day; Dose (patient ≥40 kg): 5 mg
Intervention type
Drug
Pharmaceutical study type(s)
Pharmacokinetic, Pharmacodynamic, Bioequivalence, Pharmacoeconomic
Phase
Phase IV
Drug/device/biological/vaccine name(s)
Methylprednisolone, prednisolone
Primary outcome measure
Primary clinical outcome:
Disease activity measured using the JADAS10 score at 0 weeks (Baseline) and 6 weeks
Primary economic outcomes:
1. Incremental cost per quality-adjusted life year (QALY) gained measured using Resource Use Questionnaires and Patient Level Information and Costing System (PLICS) data at 0 weeks (Baseline), 6 weeks, 12 weeks, 24 weeks and 52 weeks.
2. Resource use, costs and health utilities associated with IV and oral corticosteroids measured using Resource Use Questionnaires and Patient Level Information and Costing System (PLICS) data at 0 weeks (Baseline), 6 weeks, 12 weeks, 24 weeks and 52 weeks.
Secondary outcome measures
1. Disease activity in subjects with polyarticular Juvenile Idiopathic Arthritis (JIA) randomised to IV methylprednisolone or oral prednisolone measured using the American College of Rheumatology (ACR) Pediatric Response Criteria (30, 50, 70, 90, 100) at 0 weeks (baseline), 6 weeks, 12 weeks, 24 weeks, 52 weeks.
2. Disease activity in subjects with polyarticular Juvenile Idiopathic Arthritis (JIA), randomised to IV methylprednisolone or oral prednisolone measured using the JADAS (10,27,71) at 0 weeks (baseline), 6 weeks, 12 weeks, 24 weeks, 52 weeks.
3. Disease activity in subjects with polyarticular Juvenile Idiopathic Arthritis (JIA) randomised to IV methylprednisolone or oral prednisolone measured by JADAS10 cut-off scores at 0 weeks (baseline), 6 weeks, 12 weeks, 24 weeks, 52 weeks.
4. Pain in subjects with polyarticular Juvenile Idiopathic Arthritis (JIA) randomised to IV methylprednisolone or oral prednisolone measured using the Pain Visual Analogue Scale (Pain VAS) at 0 weeks (baseline), 6 weeks, 12 weeks, 24 weeks, 52 weeks.
5. Function in subjects with polyarticular Juvenile Idiopathic Arthritis (JIA) randomised to IV methylprednisolone or oral prednisolone measured using the Childhood Health Assessment Questionnaire (CHAQ) at 0 weeks (baseline), 6 weeks, 12 weeks, 24 weeks, 52 weeks.
6. Health-related Quality of Life (HRQoL) in subjects with polyarticular Juvenile Idiopathic Arthritis (JIA) randomised to IV methylprednisolone or oral prednisolone measured using Child Health Utility 9D Questionnaire (CHU-9D) and CAPTURE-JIA PROM at 0 weeks (baseline), 6 weeks, 12 weeks, 24 weeks, 52 weeks.
7. Requirement for additional treatment for subjects with polyarticular Juvenile Idiopathic Arthritis (JIA) due to failure to respond to IV methylprednisolone or oral prednisolone measured using concomitant medications recorded at 6 weeks, 12 weeks, 24 weeks, 52 weeks.
8. Glucocorticoid toxicity in subjects with polyarticular Juvenile Idiopathic Arthritis (JIA) randomised to IV methylprednisolone or oral prednisolone measured using Paediatric Glucocorticoid Toxicity Index (pGTI) scores at 0 weeks (baseline), 6 weeks, 12 weeks, 24 weeks, 52 weeks
Overall study start date
13/07/2023
Overall study end date
30/12/2026
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Participants must be between 1-18 years of age inclusive
2. New onset pcJIA diagnosed by a paediatric rheumatologist (to include polyarticular rheumatoid factor (RF+) positive, polyarticular RF negative, enthesitis-related arthritis, psoriatic arthritis and extended oligo-articular). This includes new diagnosis of JIA with at least 5 joints affected and patients previously categorised as oligoarticular JIA (with 4 joints or less) who have extended to at least 5 joints.
3. Participants are expected to be able to commence allocated treatment within 1 week of randomisation
4. Written, informed consent and where appropriate, assent obtained from participant or their legal representative
5. Participants of child-bearing potential must be willing to abstain from sexual intercourse from consent to their final visit and/or use another acceptable contraception method as described in section 9.10.5 of this protocol
Participant type(s)
Patient
Age group
Child
Lower age limit
1 Year
Upper age limit
18 Years
Sex
Both
Target number of participants
130
Participant exclusion criteria
1. Any contraindication to starting corticosteroids
2. Any contraindication to starting methotrexate
3. Pregnancy
4. Treatment with systemic corticosteroids within 4 weeks preceding screening (includes IV, IA, IM and oral)
5. Treatment with methotrexate within 12 weeks preceding screening
6. Any co-morbidity which in view of the treating clinician makes participation inappropriate
Recruitment start date
11/01/2024
Recruitment end date
01/10/2025
Locations
Countries of recruitment
England, Northern Ireland, United Kingdom, Wales
Study participating centre
Alder Hey Hospital
Eaton Road
West Derby
Liverpool
L12 2AP
United Kingdom
Study participating centre
University College London Hospitals NHS Foundation Trust
250 Euston Road
London
NW1 2PG
United Kingdom
Study participating centre
University Hospitals Bristol and Weston NHS Foundation Trust
Trust Headquarters
Marlborough Street
Bristol
BS1 3NU
United Kingdom
Study participating centre
University Hospitals Sussex NHS Foundation Trust
Worthing Hospital
Lyndhurst Road
Worthing
BN11 2DH
United Kingdom
Study participating centre
The Royal Belfast Hospital for Sick Children
274 Grosvenor Road
Belfast
BT12 6BA
United Kingdom
Study participating centre
Noahs Ark Childrens Hospital for Wales
Cardiff & Vale University Health Bd
Heath Park
Cardiff
CF14 4XW
United Kingdom
Sponsor information
Organisation
Alder Hey Children's NHS Foundation Trust
Sponsor details
Eaton Road
Liverpool
L12 2AP
England
United Kingdom
+44 (0)151 2824521
Kelly.Davies@alderhey.nhs.uk
Sponsor type
Hospital/treatment centre
Website
ROR
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
1. Peer-reviewed scientific journals
2. Conference presentation
3. Publication on website
4. Other publication
5. Submission to regulatory authorities
The results of STAR-JIA will be published regardless of the magnitude or direction of effect. After the primary results have been published, the anonymised individual participant data and associated documentation (protocol, statistical analysis plan, annotated blank CRF will be prepared in order to be shared with external researchers.
Dissemination animations will be created with input from PPIE group for both participants, families and the public as well as healthcare professionals to increase impact of the findings,
There is a JIA patient and public involvement focus group that contribute to development of study information sheets and animation videos for participants and parents/guardians, protocol and dissemination of results. Results of this research study will be shared with healthcare professionals, participants/care-givers and the public including medical conferences and online journals.
Intention to publish date
30/12/2027
Individual participant data (IPD) sharing plan
The current data sharing plans for this study are unknown and will be available at a later date.
IPD sharing plan summary
Data sharing statement to be made available at a later date
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|