Condition category
Musculoskeletal Diseases
Date applied
05/02/2013
Date assigned
21/03/2013
Last edited
06/04/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

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 Treatment is then continued or withdrawn depending on the biomarker levels.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 December 2016

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

Trial website

Contact information

Type

Scientific

Primary contact

Prof Dirk Foell

ORCID ID

Contact details

Roentgenstrasse 21
Muenster
D-48149
Germany

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CRA04

Study information

Scientific title

A trial to prevent disease flares by risk-adapted stratification of therapy withdrawal in juvenile idiopathic arthritis (JIA)

Acronym

PREVENT-JIA

Study hypothesis

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

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

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

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Patients and parents will be provided with written information and receive an informed consent form.

Condition

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

Phase

Not Applicable

Drug names

Primary outcome measures

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 trial start date

01/02/2013

Overall trial end date

01/12/2016

Reason abandoned

Eligibility

Participant 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.

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

100 in stratified protocol and 200 matched controls

Participant 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.

Recruitment start date

01/02/2013

Recruitment end date

01/12/2016

Locations

Countries of recruitment

Germany, Italy, Netherlands, Russian Federation, United Kingdom, United States of America

Trial participating centre

Roentgenstrasse 21
Muenster
D-48149
Germany

Sponsor information

Organisation

Interdisciplinary Center For Clinical Research Muenster (Interdisziplinäres Zentrum für Klinische Forschung) (Germany)

Sponsor details

Domagkstrasse 3
Muenster
D-48149
Germany

Sponsor type

University/education

Website

http://www.izkf.uni-muenster.de

Funders

Funder type

University/education

Funder name

Interdisciplinary Center For Clinical Research Muenster (Interdisziplinäres Zentrum für Klinische Forschung [IZKF]) at the Faculty of Medicine of the University of Muenster - CRA-04 (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

06/04/2016: Plain English summary added.