Improving outcomes for patients with rheumatoid arthritis with intermediate disease - is intensive management more effective than standard care?

ISRCTN ISRCTN70160382
DOI https://doi.org/10.1186/ISRCTN70160382
Secondary identifying numbers 15762
Submission date
16/01/2014
Registration date
16/01/2014
Last edited
26/09/2023
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Rheumatoid arthritis is a major health problem that affects one adult in a hundred. Its NHS costs exceed £500 million yearly. The main problem in rheumatoid arthritis is swollen (inflamed) joints. If persistent these cause disability and reduce quality of life. It is accepted that patients with active early rheumatoid arthritis need intensive care. This type of care results in reduction in one third of patients. Such reductions minimise disability and maximise quality of life. However, two thirds of active patients fail to achieve this reduction. Their ongoing grumbling arthritis - neither active nor in remission - means most of them are likely to become very disabled in the fullness of time with current treatment approaches. This study focuses on these patients. It is designed to find out whether intensive care results in more reduction of disease in patients with intermediate disease activity. It will also see whether intensive management reduces disability, enhances quality of life and is acceptable to patients.

Who can participate?
The study will involve men and women aged over 18 years who have a diagnosis of Rheumatoid Arthritis.

What does the study involve?
Participants will be randomly chosen to receive intensive management or standard care. Patients receiving intensive management will have monthly sessions with a specialist nurse/health practitioner, drug treatment will be optimised and treatment support regarding pain management, exercise and adherence will be given. The other group will receive standard care. All participants will be in the trial for 12 months. Patients will be assessed initially and at six and 12 months through self-completed questionnaires and clinical evaluation.

What are the possible benefits and risks of participating?
There may not be any direct benefit to participants taking part in the study; however, their arthritis will be monitored very closely by the research team, and it is hoped that this research will help improve the treatment and management of rheumatoid arthritis for all patients in the future. The risks involved in taking part in the study are small. Patients receiving intensive management are likely to receive more drug therapy. While it is possible that this will result in more side effects, there is little evidence that this will occur. This is because close monitoring and adjustment of treatment is more likely to limit the risk of side effects.

Where is the study run from?
The study will be recruiting through rheumatology departments across England. The study will be run from King's College London (UK).

When is the study starting and how long is it expected to run for?
Recruitment will begin around April 2014. Each participant is expected to be enrolled in the trial for a period of 12 months. The study is due to end in July 2017.

Who is funding the study?
The study is funded by a National Institute for Health Research (NIHR), UK.

Who is the main contact?
Dr Fowzia Ibrahim
fowzia.ibrahim@kcl.ac.uk

Study website

Contact information

Dr Fowzia Ibrahim
Scientific

Centre for Rheumatic Diseases
Department of Inflammation Biology
School of Immunology and Microbial Sciences
Faculty of Life Sciences & Medicine
King’s College London
Weston Education Centre
Room 3.55
10 Cutcombe Rd
London
SE5 9RJ
United Kingdom

ORCiD logoORCID ID 0000-0002-7069-8024
Phone 02078485771
Email fowzia.ibrahim@kcl.ac.uk

Study information

Study designRandomized controlled open interventional multicentre trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not currently available in web format. Please use the contact details to request a patient information sheet.
Scientific titleA pragmatic randomised controlled open trial of the effect of intensive management (IM) compared with standard care (SC) on remission rates at 12 months in rheumatoid arthritis patients with intermediate disease activity
Study acronymTITRATE
Study objectivesTITRATE will formally test the hypothesis that patients with established RA who currently have intermediate disease activity (defined as DAS28-ESR 3.2-5.1 with at least 3 active joints) and are currently receiving at least one DMARD, are more likely to achieve remission at 12 months if they receive intensive management than if they continue to have standard care.
Ethics approval(s)West London Research Ethics Committee, 28/10/2013, ref: 13/LO/1308
Health condition(s) or problem(s) studiedRheumatoid arthritis
InterventionThe study will compare standard care with intensive management over a period of 12 months.
Intensive management will involve monthly sessions with a trained specialist nurse or health practitioner. A management algorithm will be used to optimise drug treatment and treatment support spanning pain management, exercise and adherence will be given. Drugs will be used within their licensed indications.

The control group will receive standard care according to local and national pathways, which normally involves six-monthly clinical reviews.
Intervention typeOther
Primary outcome measureDisease remission at 12 months (final assessment) measured by the Disease Activity Score-28 (DAS28) criterion (DAS28-ESR<2.6)
Secondary outcome measures1. Alternative assessments of remission: Remission measured by the DAS28-CRP and the Simplified Disease Activity Index (SDAI) (remission defined as SDAI≤3.3) at 12 months; remission assessed by all measures at six months.
2. Assessment of Individual Components of Remission: Tender joint counts (68 joints), swollen joint counts (66
joints), patient global assessments on 100mm visual analogue scales (VAS), physician global assessments on
100mm VAS, C-Reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR) at baseline, 6 months and 12 months.
3. Disability: Health Assessment Questionnaire (HAQ) at baseline, 6 months and 12 months.
4. Joint Imaging (Predictor of future disability): Plain X-rays of the hands and feet read by a modified Larsen's score at baseline and 12 months.
5. Quality Of Life: EuroQOL 5 Dimensional score (EQ5D-5L) and patient-rated fatigue scale on 100mm VAS at baseline, six and 12 months.
6. Patient Acceptability: Modified version of the Measuring Actual Patient-led Expectations in Rheumatoid Arthritis (MAPLe-RA) questionnaire at baseline and 12 months, Medication Adherence Rating Scale (MARS) and adverse events at baseline, six and 12 months.
7. Economic Assessments: Modified Client Service Receipt Inventory (CSRI) at baseline, six and 12 months.
Overall study start date01/04/2014
Completion date14/07/2018

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants398
Total final enrolment335
Key inclusion criteriaCurrent inclusion criteria as of 11/06/2015:
1. Diagnosis of Rheumatoid Arthritis (by ACR, 2010 criteria)
2. Have received at least one DMARD for at least six months, and currently receiving at least one DMARD
3. Have intermediate disease activity, defined by:
3.1. DAS28-ESR 3.2-5.1.
3.2. At least three active joints (defined as swollen and/or tender) on 66/68 joint count, to include at least one swollen joint
4. Willing and able to follow an intensive management programme
5. Able and willing to give informed consent

Previous inclusion criteria:
1. Diagnosis of Rheumatoid Arthritis (by ACR, 2010 criteria); duration six months to 10 years
2. Have received at least one DMARD for at least six months, and currently receiving at least one DMARD
3. Have intermediate disease activity, defined by:
3.1. DAS28-ESR 3.2-5.1.
3.2. At least three swollen joints and three tender joints on 66/68 joint count
4. Willing and able to follow an intensive management programme
5. Able and willing to give informed consent
Key exclusion criteria1. Major co-morbidities making intensive treatment inadvisable (e.g. heart failure)
2. Previously failed multiple DMARDs (more than or equal to 5 treatments) or having received biologics
3. Irreversible disability from extensive joint damage (for example, replacement of three or more major joints)
4. Women who are pregnant, breastfeeding or planning to conceive
5. Currently in early RA pathway
6. Current or recent (within the previous 12 weeks) participation in another interventional trial
Date of first enrolment01/04/2014
Date of final enrolment30/06/2017

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

King's College London
London
SE5 9RJ
United Kingdom

Sponsor information

King's College London
University/education

Strand
London
WC2R 2LS
England
United Kingdom

Website http://www.kcl.ac.uk/index.aspx
ROR logo "ROR" https://ror.org/0220mzb33
King's College Hospital NHS Foundation Trust
Hospital/treatment centre

Research & Development
161 Denmark Hill
London
SE5 8EF
England
United Kingdom

Website https://www.kch.nhs.uk/
ROR logo "ROR" https://ror.org/01n0k5m85

Funders

Funder type

Government

National Institute for Health Research (NIHR) (UK) - Programme Grant for Applied Research, Ref: RP-PG-0610-10066

No information available

Results and Publications

Intention to publish date30/09/2020
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot expected to be made available
Publication and dissemination planTo be confirmed at a later date
IPD sharing planThe datasets generated during and/or analysed during the current study are not expected to be made available as there is no consent to make this data available in the public domain. However, the researchers will be able to provide an appropriate request i.e. summary participant data after review by the TITRATE team.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/10/2020 06/10/2020 Yes No
HRA research summary 28/06/2023 No No
Other publications Secondary analysis 25/09/2023 26/09/2023 Yes No

Editorial Notes

26/09/2023: Publication reference added.
19/10/2020: IPD sharing statement added.
07/10/2020: PubMed link added.
06/10/2020: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
10/01/2020: The intention to publish date has been changed from 29/07/2019 to 30/09/2020.
19/07/2019: The scientific contact was changed from Prof. David Scott <d.scott1@nhs.net> to Dr Fowzia Ibrahim <fowzia.ibrahim@kcl.ac.uk>.
18/07/2019: The intention to publish date was added.
08/08/2016: the overall trial end date was changed from 14/07/2017 to 14/07/2018.
11/06/2015: the overall trial end date was changed from 31/03/2017 to 14/07/2017.