Contact information
Type
Scientific
Primary contact
Prof Paul Bishop
ORCID ID
Contact details
Manchester Royal Eye Hospital
Oxford Road
Manchester
M13 9WH
United Kingdom
+44 (0)1612755755
Paul.Bishop@manchester.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
1.2
Study information
Scientific title
Greater Manchester Avastin® for choroidal Neovascularisation trial
Acronym
GMAN
Study hypothesis
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
South West Research Ethics Committee, ref: 07/H0206/57
Study design
Single-centre randomised controlled single-masked trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Not Applicable
Drug names
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 trial start date
03/02/2008
Overall trial end date
30/04/2011
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
330
Participant 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
Recruitment start date
03/02/2008
Recruitment end date
30/04/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Manchester Royal Eye Hospital
Manchester
M13 9WH
United Kingdom
Sponsor information
Organisation
Central Manchester & Manchester Children's Hospital NHS Trust (UK)
Sponsor details
R & D
1st Floor
Postgraduate Centre
Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom
+44 (0)1612764182
Keith.Chantler@cmmc.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
Greater Manchester NHS Primary Care Trust (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
Basic results (scientific)
Publication list