PREVENT JIA-Study: Prevention of disease flares by risk-adapted stratification of therapy withdrawal in juvenile idiopathic arthritis (JIA)
| ISRCTN | ISRCTN69963079 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN69963079 |
| Secondary identifying numbers | CRA04 |
- Submission date
- 05/02/2013
- Registration date
- 21/03/2013
- Last edited
- 14/03/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims
Juvenile idiopathic arthritis (JIA) is a type of arthritis that affects children, causing joint pain and inflammation. When the symptoms worsen, this is known as a flare. We have found that analysing patients’ white blood cell proteins (biomarkers) allows us to detect low-level inflammation and identify when patients are at risk of flares after withdrawal of treatment. The aim of this study is test a treatment approach where patients with high levels of the biomarkers continue treatment, and treatment is stopped if the levels of biomarkers are low.
Who can participate?
Children with polyarticular JIA (affecting five or more joints), who are in a stable inactive condition without any symptoms.
What does the study involve?
Patients participate in the study for a maximum of 48 months. On visits every 3 months we carry out a clinical examination and a blood test. In the first 6 months of the study participants continue to take their medication. Treatment is then continued or withdrawn depending on the biomarker levels. The biomarker tests are performed every 3 months up to 18 months. If the biomarkers stay above the threshold at the end of this period the decision to continue or stop treatment is left to the doctors. The results are compared with matched patients who are treated without using the biomarkers.
What are the possible benefits and risks of participating?
This study does not test any new medications that could lead to new risks for patients. Stopping treatment earlier in the case of low biomarker levels reduces the risk of medication side effects but could increase the risk of a relapse. If a relapse occurs, the necessary treatment will be decided by the doctor.
Where is the study run from?
University Hospital of Muenster (Germany)
When is the study starting and how long is it expected to run for?
February 2013 to August 2019
Who is funding the study?
Interdisziplinäre Zentrum für Klinische Forschung (IZKF) at the Faculty of Medicine of the University of Muenster (Germany)
Who is the main contact?
1. Prof. Dr med. Dirk Foell
2. Dr med. Dirk Holzinger
Contact information
Scientific
Roentgenstrasse 21
Muenster
D-48149
Germany
Study information
| Study design | This study will apply stratified therapeutic approaches based on a diagnostic test and hence cannot follow a randomized or blinded design for the intervention. |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Patients and parents will be provided with written information and receive an informed consent form. |
| Scientific title | A trial to prevent disease flares by risk-adapted stratification of therapy withdrawal in juvenile idiopathic arthritis (JIA) |
| Study acronym | PREVENT-JIA |
| Study objectives | The main hypothesis of this study is that JIA patients at risk of a flare due to subclinical inflammatory activity may be identified by analysis of the phagocyte activity marker S100A12/hsCRP. The goal is a stratification of the therapeutic approach: Maintenance therapy for patients with elevated levels of the biomarkers, stop of therapy if both biomarkers are low. The second major hypothesis of this study is that a risk-stratified decision on withdrawal of therapy is superior to treatment stop time point based solely upon the clinicians perspective (regarding the prevention of flares). An additional hypothesis is that the current definition of remission may be refined, adding immunological remission as a status that will be robust enough to last after discontinuing medication. |
| Ethics approval(s) | Ethics Committee of the medical association of Westfalen-Lippe and of the medical school of Wesfälische Wilhelms-Universität- Münster, 21/12/2012, ref: 2011-079-f-S |
| Health condition(s) or problem(s) studied | Juvenile arthritis |
| Intervention | The study will involve at least 100 patients (male and female, age 2-18 years) in the intervention group and 200 matched controls, recruited at hospital visits from different countries. Patients in the intervention group with biomarker driven withdrawal of therapy will be compared to matched controls with respect to the event-free interval, i.e. the time to first flare after therapy withdrawal. In the intervention group the stratification will be based upon S100A12/hsCRP levels measured in serum at each visit (i.e. every 3 months). After a watch and wait phase of 6 months in inactive disease, remission is confirmed according to the standard of care and patients will be stratified to stop therapy as soon as S100A12 is below 175 ng/ml and hsCRP is below 0.3 mg/dl. As long as any of the marker levels is above the respective threshold, patients will continue with maintenance therapy because a stable remission is not established. In the control group the duration of therapy with MTX/NSAID/Biologics is determined by the physician using any kind of clinical reasoning except the biomarker S100A12/hsCRP. |
| Intervention type | Other |
| Primary outcome measure | Event-free interval, i.e. the time to first flare after therapy withdrawal |
| Secondary outcome measures | The combined flare rate of all patients in the study will be compared to cohorts from previous studies providing robust data for a flare rate of 45%-50% after random withdrawal of therapy shown independently in several studies. As it can be expected from our trial published in JAMA and ARD that the flare rate will be only around 25%-30% with the stratified approach, we cannot withhold the chance of this superior approach from the patients included. The choice of comparisons was established in previous studies. The rationale for the biomarker to be tested, the units, and the cut offs at 175 ng/ml (S100A12) and 0.3 mg/dl (hsCRP) were established in published work. |
| Overall study start date | 01/02/2013 |
| Completion date | 31/08/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Sex | Both |
| Target number of participants | 100 in stratified protocol and 200 matched controls |
| Total final enrolment | 114 |
| Key inclusion criteria | Patients with polyarticular course of any JIA subcategory will be included at first confirmation of remission on medication, i.e. after clinically documented inactive disease for 6 months. At the time remission is documented, patients may be only on non-steroidal anti-inflammatory drugs (NSAIDs) plus DMARDs and/or biologics at a stable dose. Steroids must have beenwithdrawn at least 1 month before remission is documented. Intraarticular joint injections should not have been performed 6 months before remission is documented. |
| Key exclusion criteria | Patients with persistent oligoarthritis subtype or systemic JIA having systemic features (within 1 year prior to inclusion) are excluded. In addition, patients may not have received treatment with steroids in the month before remission is first documented or treatment with intraarticular joint injections etc. in the 6 months before remission is first documented. Patient with a history of uveitis or macrophage activation syndrome are excluded. Patients may also not be included if withdrawal of any biological drug has ever been unsuccessful in the past. |
| Date of first enrolment | 01/02/2013 |
| Date of final enrolment | 31/10/2018 |
Locations
Countries of recruitment
- Germany
- Italy
- Netherlands
- Russian Federation
- United Kingdom
- United States of America
Study participating centre
D-48149
Germany
Sponsor information
University/education
Domagkstrasse 3
Muenster
D-48149
Germany
| Website | http://www.izkf.uni-muenster.de |
|---|---|
"ROR" |
https://ror.org/00pd74e08 |
Funders
Funder type
University/education
No information available
Results and Publications
| Intention to publish date | 30/06/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in 2020 |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 08/03/2022 | 14/03/2022 | Yes | No |
Editorial Notes
14/03/2022: Publication reference added.
13/12/2021: The intention to publish date was changed from 31/12/2021 to 30/06/2022.
03/02/2021: The following changes have been made:
1. The recruitment end date has been changed from 01/12/2016 to 31/10/2018.
2. The overall trial end date has been changed from 31/12/2019 to 31/08/2019.
3. The intention to publish date has been changed from 31/12/2020 to 31/12/2021.
4. The total final enrolment number has been added.
5. The plain English summary has been updated to reflect the changes above.
17/01/2018: The overall trial end date was changed from 01/12/2016 to 31/12/2019. Publication plan, intention to publish date and participant level data were added.
06/04/2016: Plain English summary added.
