Plain English Summary
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
Trial website
Contact information
Type
Scientific
Primary contact
Dr Fowzia Ibrahim
ORCID ID
http://orcid.org/0000-0002-7069-8024
Contact details
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
02078485771
fowzia.ibrahim@kcl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
15762
Study information
Scientific title
A 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
Acronym
TITRATE
Study hypothesis
TITRATE 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
West London Research Ethics Committee, 28/10/2013, ref: 13/LO/1308
Study design
Randomised controlled open interventional multicentre trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not currently available in web format. Please use the contact details below to request a patient information sheet.
Condition
Rheumatoid arthritis
Intervention
The 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 type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
Disease remission at 12 months (final assessment) measured by the Disease Activity Score-28 (DAS28) criterion (DAS28-ESR<2.6)
Secondary outcome measures
1. 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 trial start date
01/04/2014
Overall trial end date
14/07/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
398
Total final enrolment
335
Participant exclusion criteria
1. 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
Recruitment start date
01/04/2014
Recruitment end date
30/06/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
King's College London
London
SE5 9RJ
United Kingdom
Sponsor information
Organisation
King's College London
Sponsor details
Strand
London
WC2R 2LS
United Kingdom
Sponsor type
University/education
Website
http://www.kcl.ac.uk/index.aspx
Organisation
King's College Hospital NHS Foundation Trust
Sponsor details
Research & Development
161 Denmark Hill
London
SE5 8EF
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
National Institute for Health Research (NIHR) (UK) - Programme Grant for Applied Research, Ref: RP-PG-0610-10066
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
IPD sharing statement
The 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.
Intention to publish date
30/09/2020
Participant level data
Not expected to be available
Basic results (scientific)
Publication list
2020 results in https://pubmed.ncbi.nlm.nih.gov/32931984/ (added 06/10/2020)