Condition category
Eye Diseases
Date applied
25/01/2006
Date assigned
01/02/2006
Last edited
08/02/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.cirted.org

Contact information

Type

Scientific

Primary contact

Mr Richard Lee

ORCID ID

Contact details

Department of Clinical Sciences
Bristol Eye Hospital
Lower Maudlin street
Bristol
BS1 2LX
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

CIRTED

Study hypothesis

Primary hypotheses:
To test the following hypotheses in patients being treated with prednisolone for active Thyroid Eye Disease (TED):
1. Radiotherapy (compared with placebo) induces early remission and reduces long-term disease severity
2. Combined systemic immunosuppression with oral azathioprine (compared with placebo) reduces long-term disease severity

Secondary hypotheses:
1. To test the hypothesis that patients being treated with prednisolone for active TED, using radiotherapy and combined systemic immunosuppression with oral azathioprine, can improve patient-centred outcomes and quality of life scores
2. To validate the use of a new TED specific quality of life score in the UK population
3. To improve understanding of the extent and type of psychosocial distress experienced by TED patients
4. To conduct an economic evaluation of the cost of TED and its treatment to patients, the NHS and Society
5. To compare treatments using health-economic analysis
6. To report the safety and tolerability of combined systemic immunosuppression with oral azathioprine in TED patients

Ethics approval

Central & South Bristol Research Ethics Committe (reference: 05/Q2006/62), approval gained 5th May 2005 (amendment to inclusion and exclusion criteria approved on the 2nd June 2006).

Study design

Factorial randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Patient information can be found at: http://www.cirted.org/patients.htm

Condition

Thyroid Eye Disease (TED)

Intervention

All the patients receive six months of oral prednisolone and then are randomly assigned to receive one of the following interventions:
1. Radiotherapy and azathioprine
2. Radiotherapy and placebo
3. Azathioprine and placebo
4. Control: placebo and placebo

Intervention type

Drug

Phase

Not Specified

Drug names

Azathioprine

Primary outcome measures

Primary:
1. Binary composite clinical outcome measure
2. Ophthalmopathy index

Co-primary outcome measure:
1. Clinical activity score

Secondary outcome measures

1. Total Eye Score (TES)
2. Hospital Anxiety and Depression Scale (HADS) score
3. Derriford Appearance scale-short form score
4. Graves’ Ophthalmopathy Quality of Life (GO-QoL) score
5. World Health Organisation Brief Quality of Life (WHOQoL) assessment score
6. Open-ended responses to interview questions
7. Health economic measures

Overall trial start date

01/01/2006

Overall trial end date

01/12/2008

Reason abandoned

Eligibility

Participant inclusion criteria

1. Mourits' Clinical Activity Score more than or equal to four (worst eye) or more than two (worst eye) with a history of proptosis (defined as either subjective unilateral proptosis confirmed by asymmetry in exophthalmometry of more than 2 mm or subjective bilateral proptosis) or motility restriction (defined as intermittent, inconstant or constant diplopia grade) which is less than six months long
2. Past or present history of abnormal Thyroid Gland Function (TGF) or a clinical diagnosis of TED made and confirmed by more than two muscle involvement on Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan plus a history of recent onset motility restriction and/or proptosis

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

100

Participant exclusion criteria

1. Age less than 20 or greater than 75 years
2. Optic neuropathy
3. Mourits’ Clinical Activity Score more than four without proptosis or motility restriction
4. Pre-existing glaucoma with a characteristic optic disc appearance and associated visual field defect
5. Use of radioiodine within the last three months
6. Pre-existing diabetes mellitus (not simply steroid-induced disease from recent therapy)
7. Previous adverse event associated with, or contraindication to, either prednisolone or azathioprine
8. Within six months of pregnancy, women planning pregnancy
9. Lactation
10. Haemoglobin concentration, total white cell count or platelet count below the local laboratory's reference range
11. Low, intermediate or high Thiopurine Methyltransferase (TPMT) activity
12. Lymphocyte count less than 0.8 x 10^9/l
13. Abnormal renal function (assessed by urea and creatinine levels above the local laboratory’s reference range)
14. Abnormal liver function, specifically: bilirubin, alanine aminotransferase or alkaline phosphatase concentrations above the local laboratory’s reference range
15. Malignant or pre-malignant (dysplastic) condition within the past five years
16. Previous tuberculosis
17. Shingles within the past three months
18. Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS)
19. Concurrent use of:
a. Other immunosuppressive or cytotoxic agents
b. Allopurinol
20. Live vaccines within the past three months
21. Previous orbital irradiation

Recruitment start date

01/01/2006

Recruitment end date

01/12/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Clinical Sciences
Bristol
BS1 2LX
United Kingdom

Sponsor information

Organisation

University of Bristol (UK)

Sponsor details

Research & Enterprise Development
Senate House
Tyndall Avenue
Bristol
BS8 1TH
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Research organisation

Funder name

The National Eye Research Centre, Bristol (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Special trustees of Moorfields Eye Hospital (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Charitable Trusts for the United Bristol Hospitals (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

1. 2008 protocol in http://www.ncbi.nlm.nih.gov/pubmed/18237441

Publication citations

  1. Protocol

    Rajendram R, Lee RW, Potts MJ, Rose GE, Jain R, Olver JM, Bremner F, Hurel S, Cook A, Gattamaneni R, Tomlinson M, Plowman N, Bunce C, Hollinghurst SP, Kingston L, Jackson S, Dick AD, Rumsey N, Morris OC, Dayan CM, Uddin JM, Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED) trial: a multi-centre, double-masked, factorial randomised controlled trial., Trials, 2008, 9, 6, doi: 10.1186/1745-6215-9-6.

Additional files

Editorial Notes