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Macular EpiRetinal Brachytherapy Versus Lucentis® Only Treatment (MERLOT)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
King's College Hospital NHS Trust
ClinicalTrials.gov Identifier:
NCT01006538
First received: November 2, 2009
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

Wet age-related macular degeneration is the most common cause of blind registration in the UK. Standard treatment involves regular eye injections of a drug called ranibizumab (Lucentis). For most patients, ranibizumab maintains their vision but the effect of the drug is temporary, and they therefore require monthly hospital visits and typically six injections into the eye every year, probably for life.

This study tests a new surgical device that delivers a focal dose of radiation (epimacular brachytherapy) to the macula (the part inside the back of the eye that gives fine central vision), to try and reduce or eliminate the need for ongoing, regular eye injections. The trial compares epimacular brachytherapy to ongoing standard treatment with ranibizumab.

Whereas most studies of this new surgical device target patients who have not yet commenced any treatment, this study targets those who are requiring frequent eye injections, as there are limited surgical resources and these resources are best directed to those who have not fully responded to ranibizumab therapy, or whose response is shortlived. These patients have the most to gain from a device that may reduce their burden of treatment. The findings in untreated disease cannot be extrapolated to this discrete subset of patients, hence the need for a study that targets refractory disease.

It is hypothesised that epimacular brachytherapy will reduce the frequency of Lucentis® (ranibizumab) re-treatment that patients require, whilst maintaining visual acuity.


Condition Intervention Phase
Macular Degeneration
Device: Epimacular Brachytherapy
Drug: Ranibizumab
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Controlled Trial of Epimacular Brachytherapy Versus Ranibizumab Monotherapy for the Treatment of Subfoveal Choroidal Neovascularisation Associated With Wet Age-related Macular Degeneration in Patients Who Have Commenced Anti-VEGF Therapy

Resource links provided by NLM:


Further study details as provided by King's College Hospital NHS Trust:

Primary Outcome Measures:
  • Mean change in ETDRS best-corrected visual acuity [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Mean number of re-treatment injections of Lucentis® per patient, per year. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of subjects losing < 15 ETDRS letters [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Percentage of subjects gaining ≥ 0 ETDRS letters [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Percentage of subjects gaining ≥ 15 ETDRS letters [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Change in total lesion size by fluorescein angiography [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Change in total CNV size by fluorescein angiography [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Foveal thickness measured using OCT. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 363
Study Start Date: November 2009
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (treatment)
Arm A: A single surgical procedure with epimacular brachytherapy using the VIDION® System, with Lucentis® (0.5 mg) administered on a monthly basis as required.
Device: Epimacular Brachytherapy
Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.
Other Names:
  • Vidion System
  • EpiRetinal Brachytherapy
Active Comparator: Arm B (control):
Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below.
Drug: Ranibizumab
intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Other Names:
  • Lucentis
  • Anti-VEGF therapy

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects with subfoveal choroidal neovascularisation associated with wet age-related macular degeneration. Retinal Angiomatous Proliferation (RAP) lesions not directly involving the fovea must be associated with contiguous foveal leakage demonstrated on fundus examination, OCT, or fluorescein angiography;
  2. Subjects must have received anti-VEGF induction treatment, defined as the first three months of anti-VEGF therapy. Following this induction period, subjects must have received at least 4 additional injections of Lucentis® in no more than 12 months preceding enrolment, or 2 additional injections of Lucentis® in no more than 6 months preceding enrolment, given on an as needed basis;
  3. At the time subjects commenced anti-VEGF therapy for wet age-related macular degeneration they were aged 50 years or older and met the NICE treatment criteria for Lucentis® therapy, as outlined in the Final Appraisal Determination (FAD). This states that all of the following circumstances must apply in the eye to be treated:

    • the best-corrected visual acuity is between 6/12 and 6/96 (24 to 69 ETDRS letters)
    • there is no permanent structural damage to the central fovea
    • the lesion size is less than or equal to 12 disc areas in greatest linear dimension
    • there is evidence of recent presumed disease progression (blood vessel growth, as indicated by fluorescein angiography, or recent visual acuity changes)

Exclusion Criteria:

  1. Patients who have not been treated in accordance with NICE guidance;
  2. Visual acuity worse than 6/96 at the time of study enrolment;
  3. Subjects with prior or concurrent subfoveal CNV therapy with agents, surgery or devices (other than Macugen®, Avastin®, or Lucentis®) including thermal laser photocoagulation (with or without photographic evidence), photodynamic therapy, intravitreal or subretinal steroids, and transpupillary thermotherapy (TTT);
  4. Subfoveal scarring;
  5. Subjects with active concomitant disease in the study eye, including uveitis, presence of pigment epithelial tears or rips, acute ocular or periocular infection;
  6. Subjects who have been previously diagnosed with Type 1 or Type 2 Diabetes Mellitus. Subjects who do not have a documented diagnosis, but have retinal findings consistent with Type 1 or Type 2 Diabetes Mellitus;
  7. Subjects with advanced glaucoma (greater than 0.8 cup:disk) or intraocular pressure ≥ 30 mmHg in the study eye;
  8. Previous glaucoma filtering surgery in the study eye;
  9. Subjects with inadequate pupillary dilation or significant media opacities in the study eye, including cataract, which may interfere with visual acuity or the evaluation of the posterior segment;
  10. Current vitreous haemorrhage in the study eye;
  11. History of rhegmatogenous retinal detachment or macular hole in the study eye;
  12. Subjects who present with CNV due to causes other than AMD, including subjects with known or suspected idiopathic polypoidal choroidal vasculopathy (IPCV), ocular histoplasmosis syndrome, angioid streaks, multifocal choroiditis, choroidal rupture, or pathologic myopia (spherical equivalent ≥ 8 Dioptre or axial length ≥ 25mm);
  13. Subjects who have undergone any intraocular surgery in the study eye within 12 weeks prior to the screening visit, with the exception of cataract surgery as discussed in the Exclusion Criteria #14
  14. Previous cataract surgery within 2 months prior to enrolment into the study;
  15. Subjects with known serious allergies to fluorescein dye used in angiography;
  16. Subjects with known sensitivity or allergy to Lucentis®;
  17. Subjects who underwent previous radiation therapy to the eye, head or neck;
  18. Subjects with an intravitreal device or drug in the study eye;
  19. Subjects with any other condition, which in the judgment of the investigator would prevent the subject from completing the study (e.g. documented diagnosis of dementia or serious mental illness);
  20. Current participation in another drug or device clinical trial, or participation in such a clinical trial within the last year;
  21. History of use of drugs with known retinal toxicity, including: chloroquine (Aralen - an anti-malarial drug), hydroxychloroquine (Plaquenil), phenothiazines, chlorpromazine (Thorazine), thioridazine (Mellaril), fluphenazine (Prolixin), perphenazine (Trilafon), and trifluoperazine (Stelazine);
  22. Subjects who are unwilling or unable to return for scheduled treatment and follow-up examinations for three years;
  23. Women must be post-menopausal more than 1 year unless surgically sterilised
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01006538

Locations
United Kingdom
Royal Devon and Exeter Hospital
Exeter, Devon, United Kingdom, EX2 5DW
Plymouth Royal Eye Infirmary
Plymouth, Devon, United Kingdom, PL4 6PL
Torbay Hospital
Torquay, Devon, United Kingdom, TQ2 7AA
Royal Bournemouth Hospital
Bournemouth, Dorset, United Kingdom, BH7 7DW
Sussex Eye Hospital
Brighton, East Sussex, United Kingdom, BN2 5BF
Hull and East Yorks Hospital
Hull, East Yorkshire, United Kingdom, HU3 2JZ
Essex County Hospital
Colchester, Essex, United Kingdom, CO3 3SP
Southend Hospital
Westcliff-on-Sea,, Essex, United Kingdom, SS0 0RY
Manchester Royal Eye Hospital
Manchester, Greater Manchester, United Kingdom, M13 9WH
Queen Alexandra Hospital
Portsmouth, Hampshire, United Kingdom, PO6 3LY
Maidstone Hospital
Maidstone, Kent, United Kingdom, ME16 9QQ
Ashford William Harvey Hospital
Willesborough, Kent, United Kingdom, TN24 0LZ
Royal Liverpool Hospital
Liverpool, Merseyside, United Kingdom, L7 8XP
Arrowe Park Hospital
Upton, Merseyside, United Kingdom, CH49 5PE
James Cook Hospital
Middlesborough, North Yorkshire, United Kingdom, TS4 3BW
Royal Hallamshire Hospital
Sheffield, South Yorkshire, United Kingdom, S10 2JF
Southampton Hospital
Shirley, Southampton, United Kingdom, SO16 6YD
Royal Victoria Infirmary
Newcastle, Tyne and Wear, United Kingdom, NE1 4LP
Sunderland Eye Infimary
Sunderland, Tyne and Wear, United Kingdom, SR2 9HP
Warwick Hospital Eye Unit
Warwick, Warwickshire, United Kingdom, CV34 5BW
St James University Hospital
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Bristol Eye Hospital
Bristol, United Kingdom, BS1 2LX
Darlington Memorial Hospital
Darlington, United Kingdom, DL3 6HX
King's College Hospital
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
King's College Hospital NHS Trust
Investigators
Principal Investigator: Timothy L Jackson, PhD FRCOphth King's College Hospital NHS Trust
  More Information

Additional Information:
No publications provided by King's College Hospital NHS Trust

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: King's College Hospital NHS Trust
ClinicalTrials.gov Identifier: NCT01006538     History of Changes
Other Study ID Numbers: 09/HO206/20, 2009-012509-20
Study First Received: November 2, 2009
Last Updated: March 20, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by King's College Hospital NHS Trust:
Wet Age-related Macular Degeneration
Predominantly classic
Minimally classic
Occult with no classic
Retinal Angiomatous Proliferation (RAP) lesions

Additional relevant MeSH terms:
Choroidal Neovascularization
Macular Degeneration
Choroid Diseases
Eye Diseases
Metaplasia
Neovascularization, Pathologic
Pathologic Processes
Retinal Degeneration
Retinal Diseases
Uveal Diseases

ClinicalTrials.gov processed this record on November 27, 2014