Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Macular EpiRetinal Brachytherapy Versus Lucentis® Only Treatment (MERLOT) (MERLOT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01006538
Recruitment Status : Completed
First Posted : November 3, 2009
Results First Posted : July 22, 2019
Last Update Posted : December 7, 2020
Sponsor:
Information provided by (Responsible Party):
King's College Hospital NHS Trust

Brief Summary:

Wet age-related macular degeneration is the most common cause of blind registration in the United Kingdom (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 or disease Intervention/treatment Phase
Macular Degeneration Device: Epimacular Brachytherapy Drug: Ranibizumab Phase 4

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 363 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (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
Study Start Date : November 2009
Actual Primary Completion Date : March 2015
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Ranibizumab

Arm Intervention/treatment
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 choroidal neovascular membrane (CNV) lesion. Each device is calibrated for a set duration.
Other Names:
  • Vidion System
  • EpiRetinal Brachytherapy

Drug: Ranibizumab
intravitreal injection of Ranibizumab (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Other Names:
  • Lucentis
  • Anti-VEGF therapy

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 of Ranibizumab (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Other Names:
  • Lucentis
  • Anti-VEGF therapy




Primary Outcome Measures :
  1. Mean Change in Early Treatment for Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) From Baseline to Month 12 [ Time Frame: 12 months ]

    Manifest refraction and BCVA measurements were performed according to the standard procedure originally developed for Early Treatment for Diabetic Retinopathy Study (ETDRS) and adapted for the Age Related Eye Disease Study (AREDS) protocol. Visual acuity testing was measured at a distance of 4 meters and, for subjects with sufficiently reduced vision, at 1 meter. The ETDRS charts consist of 14 lines, each comprising a series of 5 letters of equal difficulty, with standardized spacing between letters and rows (total 70 letters). Minimum is 0 (no letters read at 1 m) and maximum possible is 100 (70 letters read at 4 m + 30). If visual acuity is so poor that the subject cannot read any of the largest letters at 1 meter count fingers (CF), hand movements (HM) and light perception (PL) are tested.

    The mean change in ETDRS BCVA was calculated from baseline to month 12.


  2. Mean Number of Re-treatment Injections of Lucentis® Per Patient, Per Year. [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Percentage of Subjects Losing < 15 ETDRS Letters [ Time Frame: 12 months ]

    Manifest refraction and BCVA measurements were performed according to the standard procedure originally developed for Early Treatment for Diabetic Retinopathy Study (ETDRS) and adapted for the Age Related Eye Disease Study (AREDS) protocol. Visual acuity testing was measured at a distance of 4 meters and, for subjects with sufficiently reduced vision, at 1 meter. The ETDRS charts consist of 14 lines, each comprising a series of 5 letters of equal difficulty, with standardized spacing between letters and rows (total 70 letters). Minimum is 0 (no letters read at 1 m) and maximum possible is 100 (70 letters read at 4 m + 30). If visual acuity is so poor that the subject cannot read any of the largest letters at 1 meter count fingers (CF), hand movements (HM) and light perception (PL) are tested.

    Participants with worsening in BCVA by less than 15 EDTRS letters at month 12 compared with baseline were considered for this outcome measure.


  2. Percentage of Subjects Gaining ≥ 0 ETDRS Letters [ Time Frame: 12 months ]

    Manifest refraction and BCVA measurements were performed according to the standard procedure originally developed for Early Treatment for Diabetic Retinopathy Study (ETDRS) and adapted for the Age Related Eye Disease Study (AREDS) protocol. Visual acuity testing was measured at a distance of 4 meters and, for subjects with sufficiently reduced vision, at 1 meter. The ETDRS charts consist of 14 lines, each comprising a series of 5 letters of equal difficulty, with standardized spacing between letters and rows (total 70 letters). Minimum is 0 (no letters read at 1 m) and maximum possible is 100 (70 letters read at 4 m + 30). If visual acuity is so poor that the subject cannot read any of the largest letters at 1 meter count fingers (CF), hand movements (HM) and light perception (PL) are tested.

    Participants with an improvement in BCVA by more than 0 EDTRS letters at month 12 compared with baseline were considered for this outcome measure.


  3. Percentage of Subjects Gaining ≥ 15 ETDRS Letters [ Time Frame: 12 months ]

    Manifest refraction and BCVA measurements were performed according to the standard procedure originally developed for Early Treatment for Diabetic Retinopathy Study (ETDRS) and adapted for the Age Related Eye Disease Study (AREDS) protocol. Visual acuity testing was measured at a distance of 4 meters and, for subjects with sufficiently reduced vision, at 1 meter. The ETDRS charts consist of 14 lines, each comprising a series of 5 letters of equal difficulty, with standardized spacing between letters and rows (total 70 letters). Minimum is 0 (no letters read at 1 m) and maximum possible is 100 (70 letters read at 4 m + 30). If visual acuity is so poor that the subject cannot read any of the largest letters at 1 meter count fingers (CF), hand movements (HM) and light perception (PL) are tested.

    Participants with an improvement in BCVA by more than 15 EDTRS letters at month 12 compared with baseline were considered for this outcome measure.


  4. Change in Total Lesion Size by Fluorescein Angiography From Baseline to Month 12 [ Time Frame: 12 months ]
  5. Change in Total Choroidal Neovascular Membrane (CNV) Size by Fluorescein Angiography From Baseline to Month 12 [ Time Frame: 12 months ]
  6. Foveal Thickness Measured Using Optical Coherence Tomography (OCT) From Baseline to Month 12 [ Time Frame: 12 months ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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, optical coherence tomography (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01006538


Locations
Show Show 24 study locations
Sponsors and Collaborators
King's College Hospital NHS Trust
Investigators
Layout table for investigator information
Principal Investigator: Timothy L Jackson, PhD FRCOphth King's College Hospital NHS Trust
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: King's College Hospital NHS Trust
ClinicalTrials.gov Identifier: NCT01006538    
Other Study ID Numbers: 09/HO206/20
2009-012509-20 ( EudraCT Number )
First Posted: November 3, 2009    Key Record Dates
Results First Posted: July 22, 2019
Last Update Posted: December 7, 2020
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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:
Layout table for MeSH terms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents