Condition category
Musculoskeletal Diseases
Date applied
24/11/2010
Date assigned
25/05/2011
Last edited
04/02/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof David Scott

ORCID ID

Contact details

King's Musculoskeletal Clinical Trials Unit
Department of Academic Rheumatology
King's College London
Weston Education Centre
Cutcombe Road
Denmark Hill
London
SE5 9RJ
United Kingdom
-
d.scott1@nhs.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

OPTTIRA Protocol - Version 1.1 - 14.09.10

Study information

Scientific title

OPtimising Treatment with Tumour necrosis factor (TNF) Inhibitors in Rheumatoid Arthritis: is dose tapering practical in good responders? A 'proof of principle' and exploratory trial

Acronym

OPTTIRA

Study hypothesis

Our hypothesis is that tapering TNF inhibitors (to a minimum of one third of the initial induction doses) will not adversely affect disease control in established RA patients who have achieved a good response to standard doses of TNF inhibitors and are also receiving disease modifying anti-rheumatic drugs (DMARDs). We consider an increase of disease activity score (DAS28) at least 0.6 represents a clinical important change.

Ethics approval

North West London REC 2, 12/10/2010, ref: 10/H0720/69

Study design

Randomised controlled open-label multicentre proof of principle trial followed by an open exploratory phase trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Rheumatoid arthritis

Intervention

Patients will be randomised to one of three tapering groups:
1. Experimental group 1: patients have their TNF inhibitor tapered to 66% of initial dose by reducing frequency of dosing
2. Experimental group 2: patients have their TNF inhibitor tapered to 33% of initial dose by reducing frequency of dosing
3. Control group: patients continue on standard doses

If the proof of principle phase supports TNF inhibitor tapering, patients will enter an exploratory extension study.

Progression to the Exploratory phase for Experimental groups 1 and 2 will be based on the patient level eligibility criteria to ensure that it is appropriate for the patient to continue tapering. The Proof of Principle Control Group will have their TNF inhibitors tapered over 6 months to either 66% or 33% by reducing the frequency of their injections. Patients originally in the tapering groups will have their TNF inhibitors reduced further over 6 months by increasing the time between injections on each occasion until they are stopped completely.

Intervention type

Drug

Phase

Not Applicable

Drug names

Primary outcome measures

The development of flares, defined as an increase in DAS28 scores at least 0.6. To ensure such changes in DAS28 represent a genuine flare in RA and are not due to unrelated events (e.g. an inter-current illness like influenza) additional criteria required for a flare are:
1. It must include an increase in the swollen joint count
2. It must be present on two occasions at least one week apart
3. It results in DAS28 scores greater than 3.2

Large increases in DAS28 scores (1.2 or more) which result in DAS28 greater than 3.2 will not require any additional criteria. DAS28 measurements at baseline, 3, 6, 9 and 12 monthly assessments. The participants will also be telephoned every month to check whether their RA symptoms have increased. If it is suspected a patient is experiencing a flare, they should come in for a flare assessment within 2 weeks.

Secondary outcome measures

1. DAS28 [tender and swollen joint counts, patient global Visual Analogue Scale (VAS), erythrocyte sedimentation rate (ESR)] and Extended Joint Count 68/66, monitored at baseline, 3, 6, 9 and 12 months
2. Simple disease activity score (SDAI) and clinical disease activity score (CDAI), at baseline, 3, 6, 9 and 12 months
3. Health Assessment Questionnaire (HAQ) scores, at baseline, 3, 6, and 12 months
4. Adverse events, at baseline, 3, 6, 9 and 12 months
5. EuroQol scores, at baseline, 3, 6, and 12 months
6. SF-36, at baseline, 3, 6, and 12 months
7. Plain x-rays of the hands and feet scored by Larsens and Van Der Heijdi Sharpe Modified Scores (to provide preliminary data), at baseline, 6, and 12 months
8. Analysis of serum, immunological and gene expression profiles; biomarker blood taken at baseline for the experimental groups and at 6 months for the control group

Overall trial start date

14/12/2010

Overall trial end date

31/08/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. RA by American College of Rheumatology and EULAR criteria
2. Etanercept or adalimumab treatment for at least 6 months (a break of up to 4 consecutive weeks is permitted)
3. Taking at least one DMARD
4. Stable clinical response for at least 3 months (one DAS28 score of 3.2 or less; no increase in DAS28 greater than 0.6)
5. Patient considers he or she has achieved a suitable response to TNF inhibitors
6. Supervising rheumatologist considers further improvements are unlikely on the patients current treatment regimen
7. At least 18 years of age, either sex
8. Willing and able to give informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

99

Participant exclusion criteria

1. Serious concurrent illness (e.g. terminal cancer)
2. Prednisolone at more than 10mg daily (for doses > 10mg daily, a 4 week washout period is required)
3. Recently received intramuscular (IM)/intra-areterial (IA) steroids (12 weeks washout required)
4. Pregnancy, breast-feeding or women of child-bearing potential not using adequate contraception

Recruitment start date

14/12/2010

Recruitment end date

31/08/2013

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 (KCL) (UK)

Sponsor details

The Strand
London
WC2R 2LS
United Kingdom

Sponsor type

University/education

Website

http://www.kcl.ac.uk/index.aspx

Funders

Funder type

Charity

Funder name

Arthritis Research UK (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

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

Publication citations

Additional files

Editorial Notes

01/02/2016: No publications found, verifying study status with principal investigator