Combination photodynamic treatment and intravitreal ranibizumab versus intravitreal ranibizumab alone in neovascular age-related macular degeneration
| ISRCTN | ISRCTN42639823 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN42639823 |
| EudraCT/CTIS number | 2006-005172-40 |
| Secondary identifying numbers | EudraCT: 2006-005172-40 |
- Submission date
- 03/12/2008
- Registration date
- 05/12/2008
- Last edited
- 04/12/2012
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Eye Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Clare Bailey
Scientific
Scientific
Bristol Eye Hospital
Lower Maudlin Street
Bristol
BS1 2LX
United Kingdom
Study information
| Study design | Single-centre randomised controlled exploratory study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| 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 | A randomised prospective exploratory study comparing combination photodynamic treatment and intravitreal ranibizumab versus intravitreal ranibizumab alone in the treatment of neovascular age-related macular degeneration |
| Study objectives | This study is designed to evaluate the safety and efficacy of intravitreal ranibizumab used in combination with verteporfin photodynamic therapy (Visudyne®) for the treatment of subfoveal choroidal neovascularisation secondary to age-related macular degeneration (AMD), compared to the use of intravitreal ranibizumab alone and to see whether combination treatment reduces retreatment rates. |
| Ethics approval(s) | North Somerset and South Bristol Research Ethics Committee gave approval on the 14th February 2007 (ref: 2389) |
| Health condition(s) or problem(s) studied | Neovascular age-related macular degeneration |
| Intervention | Intravitreal ranibizumab combined with photodynamic treatment versus intravitreal ranibizumab alone: Ranibizumab 0.5 mg by intravitreal delivery. Given monthly for 3 months, then as required monthly depending on defined retreatment criteria. Total duration of treatment 1 year. For photodynamic treatment, this (or sham) is given only on the first treatment visit, and not again. Photodynamic treatment involves the intravenous administration of a drug called Visudyne®, dose depends on the body mass index of patient, followed by application of a laser to the affected eye. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Ranibizumab, verteporfin photodynamic therapy (Visudyne®) |
| Primary outcome measure | The proportion of subjects who gain 15 or more letters of best corrected visual acuity at 12 months compared to baseline, based on the ETDRS visual acuity chart. |
| Secondary outcome measures | 1. Mean change from baseline in best corrected visual acuity (BCVA) at months 6 and 12 2. Proportion of patients who gain greater than or equal to 5, greater than or equal to 10 letters of BCVA from baseline at months 6 and 12 3. Proportion of patients who lose less than 15 letters of BCVA from baseline at months 6 and 12 4. Mean change from baseline in total size of lesion and total size of CNV at 3, 6 and 12 months 5. Change in area of leakage at 3, 6 and 12 months 6. The number of treatments required with ranibizumab for each group |
| Overall study start date | 07/07/2007 |
| Completion date | 20/01/2009 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 18 |
| Key inclusion criteria | Patients (male and female aged 50 or over, no upper age limit) who at baseline: 1. Have a best-corrected logarithm of the minimum angle of resolution (logMAR) visual acuity in the study eye between 73 - 24 letters 2. Have a choroidal neovascularisation (CNV) lesion of any type in the study eye with the following characteristics as determined by fluorescein angiography: 2.1. Evidence that CNV extends under the geometric centre of the foveal avascular zone 2.2. The area of the CNV must occupy at least 50% of the total lesion 2.3. The lesion must be less than or equal to 5400 microns in greatest linear dimension (GLD) 2.4. No subfoveal atrophic change, no subfoveal fibrosis. Area of fibrosis less than or equal to 50% of total lesion area. 3. For occult with no classic CNV, the lesion must have presumed recent disease progression as assessed by the Investigator and defined as having at least one of the following criteria: 3.1. Blood associated with the lesion at baseline 3.2. Greater than or equal to 10% increase in the GLD as assessed by fluorescein angiography in the previous 3 months 3.3. Loss of VA in the previous 3 months defined as either: 3.3.1. Greater than or equal to 5 letters logMAR vision as determined by protocol refraction and protocol measurement, or 3.3.2. Two or more lines using a Snellen chart by standard examination |
| Key exclusion criteria | 1. Prior treatment with external-beam radiation therapy, transpupillary thermotherapy (TTT), thermal laser, or verteporfin therapy (PDT) in the study eye 2. Treatment with verteporfin in the non-study eye less than 7 days preceding Day 0 3. Previous participation in a clinical trial (for either eye) involving anti-angiogenic drugs (Macugen®, Avastin®, anecortave acetate, protein kinase C inhibitors, etc.) 4. Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection or device implantation) in the study eye 5. History of vitrectomy surgery in the study eye 6. History of greater than mild non-proliferative diabetic retinopathy or any diabetic maculopathy 7. History of retinal vascular occlusions 8. History of glaucoma filtering surgery in the study eye 9. History of corneal transplant in the study eye 10. History of submacular surgery or other surgical intervention for AMD in the study eye 11. Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals) 12. Subretinal haemorrhage in the study eye that involves the centre of the fovea, if the size of the haemorrhage is either greater than 50% of the total lesion area or greater than 1 disc area in size 13. Subfoveal fibrosis or atrophy in the study eye. Area of fibrosis greater than 50% of total lesion area. 14. CNV in either eye due to causes other than AMD, such as ocular histoplasmosis, trauma, or pathologic myopia 15. Retinal pigment epithelial tear involving the macula in the study eye 16. Any concurrent intraocular condition in the study eye (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, could either require medical or surgical intervention during the 12-month study period to prevent or treat visual loss that might result from that condition, or if allowed to progress untreated, could likely contribute to loss of at least two Snellen equivalent lines of best corrected visual acuity over the 12-month study period 17. Active intraocular inflammation (grade trace or above) in the study eye 18. Current vitreous haemorrhage in the study eye 19. History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye 20. History of idiopathic or autoimmune-associated uveitis in either eye 21. Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye 22. Aphakia or absence of the posterior capsule in the study eye 23. Previous violation of the posterior capsule in the study eye is also excluded unless it occurred as a result of YAG posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation 24. Spherical equivalent of the refractive error in the study eye demonstrating more than -8 diopters of myopia or signs of pathologic myopia with a refraction of 4 - 8 diopters 25. For subjects who have undergone prior refractive or cataract surgery in the study eye, the pre-operative refractive error in the study eye cannot exceed -8 diopters of myopia 26. Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Day 0 27. Uncontrolled glaucoma in the study eye (defined as intraocular pressure greater than 30 mmHg despite treatment with anti-glaucoma medication) 28. Concurrent systemic conditions 29. Premenopausal women not using adequate contraception. The following are considered effective means of contraception: 29.1. Surgical sterilisation 29.2. Use of oral contraceptives 29.3. Barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel 29.4. An intrauterine device (IUD) 29.5. Contraceptive hormone implant or patch 30. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications 31. Current treatment for active systemic infection 32. Recent stroke, or cardiac event, uncontrolled angina or hypertension 33. History of allergy to fluorescein 34. Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analysed 35. Inability to comply with study or follow-up procedures |
| Date of first enrolment | 07/07/2007 |
| Date of final enrolment | 20/01/2009 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Bristol Eye Hospital
Bristol
BS1 2LX
United Kingdom
BS1 2LX
United Kingdom
Sponsor information
University Hospitals Bristol NHS Foundation Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Research and Effectiveness Department
Level 3 Education Centre
Upper Maudlin Street
Bristol
BS2 8AE
England
United Kingdom
| Website | http://www.uhbristol.nhs.uk/research |
|---|---|
"ROR" |
https://ror.org/04nm1cv11 |
Funders
Funder type
Industry
Novartis Pharmaceuticals (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 |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/10/2010 | Yes | No |
