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

Plain English Summary

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

Study website

http://www.tacit.org.uk

Type

Scientific

Contact name

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

EudraCT/CTIS number

2007-001190-28

IRAS number

ClinicalTrials.gov number

Protocol/serial number

HTA 06/303/84; KCL (Rheum) TACIT Version 1 (26/01/07)

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(s)

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

Study setting(s)

Hospital

Study 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

Pharmaceutical study type(s)

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

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 study start date

01/04/2007

Overall study end date

31/03/2010

Reason abandoned (if study stopped)

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(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

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

Countries of recruitment

England, United Kingdom

Study participating centre

King's College London
London
SE5 9RJ
United Kingdom

Organisation

King's College London (UK)

Sponsor details

Strand
London
WC2R 2LS
England
United Kingdom
+44 (0)20 7836 5454
ceu@kcl.ac.uk

Sponsor type

University/education

Website

http://www.kcl.ac.uk

ROR

https://ror.org/0220mzb33

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

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Individual participant data (IPD) sharing plan

Not provided at time of registration

IPD sharing plan summary

Not provided at time of registration

Study outputs