Randomised controlled trial of tumour necrosis factor inhibitors against combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis

ISRCTN	ISRCTN37438295
DOI	https://doi.org/10.1186/ISRCTN37438295
Clinical Trials Information System (CTIS)	2007-001190-28
Protocol serial number	HTA 06/303/84; KCL (Rheum) TACIT Version 1 (26/01/07)
Sponsor	King's College London (UK)
Funder	Health Technology Assessment Programme

Submission date: 11/06/2007
Registration date: 12/06/2007
Last edited: 29/09/2022

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

http://www.medscinet.net/TACIT/patientinfodocs/Summary%20PIS%20Version%201%20%2820.12.07%29.pdf

Contact information

Prof David L Scott
Scientific

Department of Academic Rheumatology
King's College London
Weston Education Centre
Cutcombe Road
Denmark Hill
London
SE5 9RJ
United Kingdom

Phone	+44 (0)20 7848 5215
Email	david.l.scott@kcl.ac.uk

Study information

Primary study design	Interventional
Study design	Two-arm pragmatic 12-month randomised controlled multi-centred trial using open-label treatments
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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
Study acronym	TACIT
Study objectives	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(s)	Research ethics committee of the UCLH A, 20/04/2007, ref: 07/Q0505/57
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Adalimumab, etanercept, infliximab, methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, ciclosporin and gold injections (sodium aurothiomalate)
Primary outcome measure(s)	Heath Assessment Questionnaire (HAQ). Primary and secondary outcomes will be measured at baseline (month 0), 6 months and 12 months.
Key secondary outcome measure(s)	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.
Completion date	31/03/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	190
Key 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)
Key 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)
Date of first enrolment	01/04/2007
Date of final enrolment	31/03/2010

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

King's College London

London
SE5 9RJ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/10/2014		Yes	No
Results article	results	13/03/2015		Yes	No
Results article	cost-effectiveness results	01/03/2020	13/07/2020	Yes	No
Results article	Characterization of missing data patterns and mechanisms	17/09/2022	29/09/2022	Yes	No
Other publications	secondary analysis	26/08/2016		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

29/09/2022: Publication reference added.
13/07/2020: Publication reference added.
22/09/2016: Publication reference added.