Plain English Summary
http://www.medscinet.net/TACIT/patientinfodocs/Summary%20PIS%20Version%201%20%2820.12.07%29.pdf
Trial website
Contact information
Type
Scientific
Primary contact
Prof David L Scott
ORCID ID
Contact details
Department of Academic Rheumatology
King's College London
Weston Education Centre
Cutcombe Road
Denmark Hill
London
SE5 9RJ
United Kingdom
+44 (0)20 7848 5215
david.l.scott@kcl.ac.uk
Additional identifiers
EudraCT number
2007-001190-28
ClinicalTrials.gov number
Protocol/serial number
HTA 06/303/84; KCL (Rheum) TACIT Version 1 (26/01/07)
Study information
Scientific title
Randomised controlled trial of Tumour necrosis factor inhibitors Against Combination Intensive Therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis
Acronym
TACIT
Study hypothesis
Active Rheumatoid Arthritis (RA) patients, who meet the National Institute for Clinical Excellence (NICE) criteria for treatment with Tumour Necrosis Factor (TNF) inhibitors, will gain equivalent benefit from intensive combination therapy (two or more Disease Modifying Anti-Rheumatic Drugs [DMARDs] and steroids) at substantially less expense and without increased toxicity.
More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/0630384
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0003/51339/PRO-06-303-84.pdf
Ethics approval
Research ethics committee of the UCLH A, 20/04/2007, ref: 07/Q0505/57
Study design
Two-arm pragmatic 12-month randomised controlled multi-centred trial using open-label treatments
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
http://www.medscinet.net/tacit/patientinfo.aspx?id=1
Condition
Rheumatoid arthritis
Intervention
There will be two treatment algorithms:
1. For TNF inhibitors, and
2. For combination DMARDs
Treatments will be individualised and will depend on patients' responses.
TNF inhibitors:
All three licensed agents - adalimumab, etanercept, and infliximab - will be allowed at standard doses (British National Formulary). The choice of TNF inhibitor will reflect patient's preferences and local circumstances. Methotrexate will also be given to maximise efficacy and (in the case of infliximab) reduce anti-chimeric antibodies. Any patient intolerant to methotrexate may take another DMARD.
Combination DMARDs:
DMARDs from the following list will be used: methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, ciclosporin and gold injections (sodium aurothiomalate) in combinations with proven efficacy over DMARD monotherapy in Randomised Controlled trials (RCTs). For example:
1. Triple therapy with methotrexate (methotrexate-sulfasalazine-hydroxychloroquine)
2. Other methotrexate combinations (methotrexate-ciclosporin, methotrexate-leflunomide and methotrexate-gold)
3. One sulfasalazine combination (sulfasalazine-leflunomide)
Additional monthly steroids (intramuscular [IM] depomedrone [120 mg stat] or equivalent) will also be used if needed.
The duration of treatment is one year and patients are followed for only this year.
Intervention type
Drug
Phase
Phase IV
Drug names
Adalimumab, etanercept, infliximab, methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, ciclosporin and gold injections (sodium aurothiomalate)
Primary outcome measure
Heath Assessment Questionnaire (HAQ).
Primary and secondary outcomes will be measured at baseline (month 0), 6 months and 12 months.
Secondary outcome measures
1. Joint damage
2. Quality of life
3. Disease activity
4. Withdrawal rates
5. Adverse effects
6. Economic evaluation:
6.1. Societal costs
6.2. Cost-effectiveness
6.3. Cost-utility
Primary and secondary outcomes will be measured at baseline (month 0), 6 months and 12 months. Patients will be asked to attend monthly for blood monitoring and will be asked a short questionnaire regarding concomitant medication, any tests outside routine monitoring and adverse events within the last month.
Overall trial start date
01/04/2007
Overall trial end date
31/03/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Males and females aged over 18 years
2. Established RA by the criteria of the American College of Rheumatology
3. Disease duration of at least 12 months
4. Meet NICE criteria for being prescribed TNF inhibitors:
4.1. Disease Activity Score (DAS) over 5.1
4.2. Failure to respond to two DMARDs including methotrexate
4.3. No contra-indications to TNF inhibitors (including possibility of pregnancy)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
190
Participant exclusion criteria
1. Unable or unwilling to give informed consent
2. Failure of, or contra-indications to, all proposed DMARD combinations (including possibility of pregnancy)
3. Serious inter-current illness
4. Patients on high dose steroids (in excess of 10 mg prednisolone or equivalent per day at trial entry)
Recruitment start date
01/04/2007
Recruitment end date
31/03/2010
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 (UK)
Sponsor details
Strand
London
WC2R 2LS
United Kingdom
+44 (0)20 7836 5454
ceu@kcl.ac.uk
Sponsor type
University/education
Website
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
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25351370
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25769495
2016 secondary analysis in: http://www.ncbi.nlm.nih.gov/pubmed/27651924
Publication citations
-
Results
Scott DL, Ibrahim F, Farewell V, O'Keeffe AG, Ma M, Walker D, Heslin M, Patel A, Kingsley G, Randomised controlled trial of Tumour necrosis factor inhibitors Against Combination Intensive Therapy with conventional disease-modifying antirheumatic drugs in established rheumatoid arthritis: the TACIT trial and associated systematic reviews., Health Technol Assess, 2014, 18, 66, 1-164, doi: 10.3310/hta18660.
-
Results
Scott DL, Ibrahim F, Farewell V, O'Keeffe AG, Walker D, Kelly C, Birrell F, Chakravarty K, Maddison P, Heslin M, Patel A10, Kingsley GH, Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial., BMJ, 2015, 350, h1046, doi: 10.1136/bmj.h1046.