Condition category
Eye Diseases
Date applied
15/04/2008
Date assigned
16/04/2008
Last edited
28/03/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Richard Lee

ORCID ID

Contact details

Academic Unit of Ophthalmology
Bristol Eye Hospital
Lower Maudlin Street
Bristol
BS1 2LX
United Kingdom
+44 (0)117 928 4949
richard.lee@bristol.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

OP/2004/1733

Study information

Scientific title

Dual steroid and tacrolimus therapy versus steroid withdrawal and tacrolimus therapy in the treatment of posterior segment intraocular inflammation (uveitis)

Acronym

Study hypothesis

Tacrolimus monotherapy is not inferior to tacrolimus and prednisolone for the maintenance of uveitis remission.

Ethics approval

Ethics approval received from North Somerset and South Bristol Research Ethics Committee on the 8th March 2004 (ref: E5862).

Study design

Dual-centre, randomised, non-inferiority, open-label 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

Uveitis

Intervention

1. Oral tacrolimus (target trough serum level 8 - 12 ng/ml) only
2. Oral tacrolimus (target trough serum level 8 - 12 ng/ml) and oral prednisolone (7.5 - 10 mg daily)

Frequency of oral tacrolimus administration is the same for both trial arms. It is administered twice daily, however the oral dose prescribed to achieve the target serum levels varies from patient to patient. Treatment duration and follow-up are until study completion (i.e., nine months post randomisation), or withdrawal.

Intervention type

Drug

Phase

Not Specified

Drug names

Tacrolimus, prednisolone

Primary outcome measures

Change in logarithm of the minimum angle of resolution (LogMAR) visual acuity (VA) between randomisation and study completion or withdrawal.

Secondary outcome measures

1. Rate of study withdrawal post-randomisation due to either treatment inefficacy (disease reactivation) or intolerance
2. Change in the following measures of disease severity between randomisation and study completion or withdrawal:
2.1. Binocular indirect ophthalmoscopy score
2.2. Anterior chamber cell grade
2.3. Retinal vasculitis score
2.4. Grade of optic disc swelling
2.5. Chorioretinal infiltrate
3. Change in the following assessments of treatment tolerance between randomisation and study completion or withdrawal:
3.1. Rate of onset of hypocholesterolemia, hypoglycaemia, hypertension, hypomagnesaemia and greater than or equal to 30% increase in serum creatinine concentration
3.2. Rate of onset of adverse events - overall by system (e.g. nervous system) and by description (e.g. tremor)
3.3. Rate of increase in intraocular pressure (IOP) to greater than 24 mmHg
4. Proportion of patients withdrawn post-enrolment and pre-randomisation for treatment inefficacy or intolerance
5. Change in quality of life in 3, 6 and 12 months after study enrolment, as assessed by the 36-item short form health survey (SF-36) and vision core module 1 (VCM1) scores

Overall trial start date

01/05/2004

Overall trial end date

01/12/2008

Reason abandoned

Eligibility

Participant inclusion criteria

Patients with sight-threatening non-infectious posterior intraocular inflammation (PSII) who:
1. Are unable to reduce their prednisone dose to less than 10 mg daily without disease relapse
2. Require recurrent high dose steroid rescue for recurrent relapsing disease
3. Have severe sight-threatening disease warranting immediate institution of combination immunotherapy (high dose prednisone and a second line agent)
4. Are greater than or equal to 18 years old, either sex, and able to give informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40

Participant exclusion criteria

1. Pregnancy or lactation
2. Female patients of child bearing age who are unwilling or unable to maintain effective birth control during the study
3. Diabetes mellitus (except steroid induced)
4. Significant and unstable renal disease (creatinine outside the local laboratories reference range on two consecutive occasions)
5. Participating in another clinical trial or has been taking an investigational drug in the past 28 days
6. Unlikely to comply with the visits scheduled in the protocol
7. Live vaccinations within three months of study entry
8. Previous adverse event associated with, or contra-indication to, either prednisolone or tacrolimus
9. Concurrent use of other immunosuppressive or cytotoxic agents
10. Previous tuberculosis
11. Shingles within the past three months
12. Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), including current or previous history of opportunistic infections such as cytomegalovirus (CMV), active Pneumocystis carinii, atypical mycobacterium
13. Recent history of substance abuse (drug or alcohol)
14. Use of cyclosporin A within the last three months
15. Serious infections, such as hepatitis, pneumonia, pyelonephritis in the previous three months

Recruitment start date

01/05/2004

Recruitment end date

01/12/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Academic Unit of Ophthalmology
Bristol
BS1 2LX
United Kingdom

Sponsor information

Organisation

United Bristol Healthcare Trust (UK)

Sponsor details

Research and Effectiveness Department
UBHT Education Centre
Level 3
Upper Maudlin Street
Bristol
BS2 8AE
United Kingdom

Sponsor type

Government

Website

http://www.ubht.nhs.uk/

Funders

Funder type

Industry

Funder name

Fujisawa Pharma Co Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

NHS R&D support funding (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. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22381809

Publication citations

  1. Results

    Lee RW, Greenwood R, Taylor H, Amer R, Biester S, Heissigerova J, Forrester JV, Dick AD, A randomized trial of tacrolimus versus tacrolimus and prednisone for the maintenance of disease remission in noninfectious uveitis., Ophthalmology, 2012, 119, 6, 1223-1230, doi: 10.1016/j.ophtha.2011.12.030.

Additional files

Editorial Notes