Condition category
Musculoskeletal Diseases
Date applied
11/06/2007
Date assigned
12/06/2007
Last edited
22/09/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 measures

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

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

http://www.kcl.ac.uk

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

Federal/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

Results - basic reporting

Publication summary

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

  1. 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.

  2. 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.

Additional files

Editorial Notes

22/09/2016: Publication reference added.