Study protocol

Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED) trial: A multi-centre, double-masked, factorial randomised controlled trial

Rathie Rajendram¹ , Richard WJ Lee^2,3 , Mike J Potts³ , Geoff E Rose¹ , Rajni Jain⁴ , Jane M Olver⁴ , Fion Bremner⁵ , Steven Hurel⁶ , Anne Cook⁷ , Rao Gattamaneni⁸ , Marjorie Tomlinson⁹ , Nicholas Plowman¹⁰ , Catey Bunce¹ , Sandra P Hollinghurst¹¹ , Laura Kingston¹² , Sue Jackson¹² , Andrew D Dick^2,3 , Nichola Rumsey¹² , Olivia C Morris¹ , Colin M Dayan¹³ and Jimmy M Uddin¹

¹  Moorfields Eye Hospital, City Road, London EC1V 2PD, UK

²  Department of Clinical Science at South Bristol, University of Bristol, UK

³  Bristol Eye Hospital, Lower Maudlin Street, Bristol, BS1 2LX, UK

⁴  Western Eye Hospital, Marylebone Road, London, NW1 5YE, UK

⁵  Department of Neuroophthalmology, Internal Box 142, The National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N3BG, UK

⁶  University College London Hospital, Third Floor East, 250 Euston Road, London, NW1 2PQ, UK

⁷  Manchester Royal Eye Hospital, Oxford Road, Manchester. M13 9WH, UK

⁸  Christie Hospital, Wilmslow Road, Manchester, M20 4BX, UK

⁹  Bristol Haematology and Oncology Centre, Horfield Road, Bristol, BS2 8ED, UK

¹⁰  St Bartholomew's Hospital, West Smithfield, London, EC1A 7BE, UK

¹¹  Academic Unit of Primary Health Care, Department of Community Based Medicine, University of Bristol, 25 Belgrave Road, Bristol, BS8 2AA, UK

¹²  Centre for Appearance Research, University of the West of England, Fishponds, Bristol, BS16 2JP, UK

¹³  Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK

author email corresponding author email

Trials 2008, 9:6doi:10.1186/1745-6215-9-6

Published:	31 January 2008

Abstract

Background

Medical management of thyroid eye disease remains controversial due to a paucity of high quality evidence on long-term treatment outcomes. Glucocorticoids are known to be effective initially but have significant side-effects with long-term use and recrudescence can occur on cessation. Current evidence is conflicting on the efficacy of radiotherapy and non-steroid systemic immunosuppression, and the majority of previous studies have been retrospective, uncontrolled, small or poorly designed.

The Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease (CIRTED) trial was designed to investigate the efficacy of radiotherapy and azathioprine in combination with a standard course of oral prednisolone in patients with active thyroid eye disease.

Methods/design

Patients with active thyroid eye disease will be randomised to receive (i) azathioprine or oral placebo and (ii) radiotherapy or sham-radiotherapy in this multi-centre, factorial randomised control trial. The primary outcome is improvement in disease severity (assessed using a composite binary measure) at 12 months and secondary end-points include quality of life scores and health economic measures.

Discussion

The CIRTED trial is the first study to evaluate the role of radiotherapy and azathioprine as part of a long-term, combination immunosuppressive treatment regime for Thyroid Eye Disease. It will provide evidence for the role of radiotherapy and prolonged immunosuppression in the management of this condition, as well as pilot data on their use in combination. We have paid particular attention in the trial design to establishing (a) robust placebo controls and masking protocols which are effective and safe for both radiotherapy and the systemic administration of an antiproliferative drug; (b) constructing effective inclusion and exclusion criteria to select for active disease; and (c) selecting pragmatic outcome measures.

Trial registration

Current controlled trials ISRCTN22471573