Condition category
Eye Diseases
Date applied
25/02/2008
Date assigned
31/07/2008
Last edited
21/07/2014
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

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

Acronym

GMAN

Study hypothesis

Disease studied: Wet age-related macular degeneration (AMD). There are two forms of AMD sometimes referred to as 'dry' and 'wet' macular degeneration. The 'wet' form accounts for about 10% of AMD but, because it is the more severe form, accounts for 90% of blind registrations due to AMD. The 'wet' form of AMD is caused by choroidal neovascularisation (CNV) i.e. abnormal new blood vessels derived from the choroid growing into the macula (the central part of the retina that is used for detailed vision) and from hereon will be referred to as neovascular AMD. These new blood vessels leak and bleed and eventually a scar forms, this process results in the progressive loss of central vision. Furthermore, the condition frequently affects both eyes.

The purpose 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 measures

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

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 0.3–1.2 (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

http://www.cmmc.nhs.uk

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes