Greater Manchester Avastin® for choroidal Neovascularisation trial

ISRCTN	ISRCTN34221234
DOI	https://doi.org/10.1186/ISRCTN34221234
Secondary identifying numbers	1.2

Submission date: 25/02/2008
Registration date: 31/07/2008
Last edited: 12/04/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Eye Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Paul Bishop
Scientific

Manchester Royal Eye Hospital
Oxford Road
Manchester
M13 9WH
United Kingdom

Phone	+44 (0)1612755755
Email	Paul.Bishop@manchester.ac.uk

Study information

Study design	Single-centre randomised controlled single-masked trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Greater Manchester Avastin® for choroidal Neovascularisation trial
Study acronym	GMAN
Study objectives	The aim of the study is to demonstrate that a treatment regime over 12 and 24 months where intravitreal bevacizumab for treatment of neovascular age-related macular degeneration is given monthly for three months and then on a prn ('when necessary') basis at three monthly intervals, the 'PRN' treatment arm, is not inferior to a regime where bevacizumab is given monthly for three months and then every three months irrespective of clinical symptoms and signs, the 'Routine' treatment arm, with respect to best-corrected visual acuity (BCVA).
Ethics approval(s)	South West Research Ethics Committee, ref: 07/H0206/57
Health condition(s) or problem(s) studied	Age-related macular degeneration
Intervention	Initially, all participants will be treated with 1.25 mg intravitreal bevacizumab (Avastin®) on Day 1 and 1 and 2 months. After this period, the 'Routine' treatment arm will receive 1.25 mg bevacizumab at 5, 8, 11, 14,17, 20 and 23 months, and the 'PRN' arm will receive the same treatment only when clinical signs of deterioration of vision or progression of the CNV lesion are observed. All patients will be seen by a clinician at Day 1 and 1, 2, 5, 8, 11, 14, 17, 20 and 23 months. There will be a final assessment visit at month 24. If patients suffer a marked drop in vision of more than 5 letters from the best corrected visual acuity recorded three months earlier there will be an additional interim treatment visit 6 weeks later aimed at stabilising the vision.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Bevacizumab (Avastin®)
Primary outcome measure	1. Visual acuity outcomes. Duration of follow-up: 24 months 2. Safety: adverse event reports and vital signs. Duration of follow-up: 24 months
Secondary outcome measures	1. Investigation of equivalence between two arms using additional measures of visual function including contrast sensitivity (CS), reading speed (RS), and radial deformation acuity (RDA) 2. To evaluate the efficacy of the two bevacizumab treatment regimes by changes in visual function (BCVA, CS, RS, and RDA) from baseline over 11 and 24 months 3. To determine the mean number of treatments required in the PRN treatment arm after month 2 and for the patients that require further treatments after month 2 the mean time interval until this retreatment is required 4. To investigate the correlation between BCVA and additional measures of visual function (CS, RS, and RDA), and assess the variability of these measures over time, to establish the clinical usefulness of these measures in determining change over time in patients with CNV 5. To evaluate the efficacy of the two bevacizumab treatment regimes by measuring changes from baseline of OCT and FFA parameters over 11 and 24 months 6. To explore the temporal changes in BCVA at months 1, 2 and 3 to evaluate the onset of treatment effect 7. To undertake pharmacogenetic studies to determine whether any variations in treatment response can be attributed to identifiable genetic variations
Overall study start date	03/02/2008
Completion date	30/04/2011

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Both
Target number of participants	330
Key inclusion criteria	1. Men or women of any ethnic background over the age of 50 years with AMD 2. Subfoveal choroidal neovascularisation or juxtafoveal choroidal neovascularisation where laser would ablate the centre of the foveal avascular zone (FAZ) 3. Predominantly-classic CNV or minimally classic or occult with no classic CNV lesion composition where there is evidence of recent disease progression (i.e. vision loss, lesion growth on fundus fluorescein angiogram [FFA], progression on optical coherence tomography [OCT] examination, new blood associated with lesion within the preceding three months) 4. The total area of CNV within the lesion (including classic and occult components) must be greater than 50% of the lesion area as defined by FFA 5. The BCVA letter score must be between logMAR 0.31.2 (approximately 6/12 to 6/96 Snellen equivalent) 6. Patients must have completed study consent forms and must be willing and able to comply with all of the study protocols
Key exclusion criteria	1. Prior treatment to the CNV lesion 2. Lesion components including fibrosis, haemorrhage or serous pigment epithelial detachment representing greater than 50% of the lesion 3. Retinal pigment epithelial tear (rip) 4. Active intraocular inflammation within one month of screening for study 5. Active or suspected ocular or periocular infection 6. Uncontrolled glaucoma in study eye (intra-ocular pressure [IOP] of greater than 25 mmHg despite anti-glaucomatous medication) 7. History of ocular surgery or YAG (yttrium aluminium garnet) laser capsulotomy within two months of screening for study 8. History of allergy to fluorescein 9. Any systemic medication that may interfere with the safety of the patient or is known to be toxic to the retina 10. Uncontrolled hypertension 11. Within one month of major surgery 12. History of myocardial infarction, stroke or gastrointestinal perforation 13. Episode of angina or transient ischaemic attack within 6 months of screening 14. Pregnant and or lactating women 15. Women of childbearing potential (i.e. not sterilised or not post menopausal) who are unwilling to use effective contraception during the study and for 6 months after Bevacizumab treatment has stopped 16. Men with a spouse or partner with childbearing potential unless the participant has agreed to use condoms
Date of first enrolment	03/02/2008
Date of final enrolment	30/04/2011

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Manchester Royal Eye Hospital

Manchester
M13 9WH
United Kingdom

Sponsor information

Central Manchester & Manchester Children's Hospital NHS Trust (UK)
Hospital/treatment centre

R & D, 1st Floor
Postgraduate Centre
Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
England
United Kingdom

Phone	+44 (0)1612764182
Email	Keith.Chantler@cmmc.nhs.uk
Website	http://www.cmmc.nhs.uk
"ROR"	https://ror.org/00he80998

Funders

Funder type

Government

Greater Manchester NHS Primary Care Trust (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

12/04/2017: No publications found in PubMed, verifying study status with principal investigator