Triple Therapy - PDT Plus IVD and Intravitreal Ranibizumab Versus Lucentis Monotherapy to Treat Age-Related Macular Degeneration

NCT ID: NCT00390208

Last Updated: 2010-05-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-08-31

Study Completion Date

2009-12-31

Brief Summary

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The purpose of this study is to compare triple therapy using Photodynamic therapy, intravitreal Dexamethasone and intravitreal Ranibizumab injections versus monotherapy with intravitreal Ranibizumab alone for the treatment of Age-Related Macular Degeneration.

Detailed Description

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This is a twelve month Phase II prospective masked study comparing Group 1 triple therapy: Same day combination therapy with PDT, 500 microgram dose (0.05cc) intravitreal dexamethasone injection (10mg/ml vial), and a single 0.5 mg intravitreal Ranibizumab injection. This will be compared to Group 2 monotherapy: one intravitreal injection of 0.5 mg Lucentis given every four weeks on a set dosing schedule. Sixty consecutive patients will be enrolled into this clinical trial utilizing the current standard of care guidelines as used at Bay Area Retina Associates. Angiography, fundus photography will be performed at the initial visit and quarterly follow-up visits. Only OCT testing will be performed at all other follow-up visits. Both groups will be re-evaluated for safety at 12 and 24 months.

Group 1 Following the initial treatment, all future re-treatments with Lucentis will be determined on a PRN basis. The decision will be based on clinical examination and imaging evidence of lesion activity. Any evidence of subretinal fluid or cystoid edema on OCT or clinical examination, or evidence of leakage on angiogram will result in re-treatment. If after three consecutive Ranibizumab injections in Group 1, there is any evidence of lesion recurrence or growth of the neovascular membrane associated with visual decline or persistent subretinal fluid, the patient will be treated with repeat PDT/IVD/Lucentis The decision to retreat Group 1 with ranibizumab at each monthly follow-up visit will be dependent on clinical exam, OCT measurements or angiographic findings as documented below.

Group 2 Subjects will receive one intravitreal injection of 0.5 mg Lucentis every four weeks until week 48 or as indicated on the FDA approval label.

Conditions

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Age Related Macular Degeneration

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Group 1

Combination triple therapy of Lucentis, Dexamethasone and Visudyne Therapy

Group Type OTHER

ranibizumab, dexamethasone and verteporfin

Intervention Type DRUG

One 500 microgram dose (0.05cc) intravitreal dexamethasone (10 mg/ml vial) in combination with Visudyne Photodynamic Therapy and 0.5 mg intravitreal Ranibizumab injection on the same day.

Group 2

Monotherapy: One 0.5 mg intravitreal Ranibizumab injection

Group Type OTHER

Ranibizumab

Intervention Type DRUG

One 0.5 mg intravitreal Ranibizumab injection

Interventions

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ranibizumab, dexamethasone and verteporfin

One 500 microgram dose (0.05cc) intravitreal dexamethasone (10 mg/ml vial) in combination with Visudyne Photodynamic Therapy and 0.5 mg intravitreal Ranibizumab injection on the same day.

Intervention Type DRUG

Ranibizumab

One 0.5 mg intravitreal Ranibizumab injection

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Best Corrected Visual Acuity using ETDRS Charts between 20/32 and 20/400 (Snellen Equivalent) in the study eye with evidence of neovascular ARMD.

(Only one eye will be eligible for study. If both eyes are eligible, the one with the better visual acuity will be selected for treatment unless, based on medical reasons, the investigator deems the other eye to be more appropriate for treatment and study.)

* All lesion subtypes will be enrolled with the following criteria

* Predominantly classic:
* Classic lesion greater than 50% of the total lesion area
* Lesion must be less than 12 disc areas

* Minimally classic or occult:
* CNVM must be greater than or equal to 50% of the total lesion size.
* There must be some evidence of recent disease progression (heme, vision loss, recent lesion growth on FA)
* Lesion size must be less than 12 disc areas.

* Occult:
* Lesions must show recent activity progression with respect to vision, subretinal hemorrhage or subretinal fluid
* Less than 12 disc areas in total size
* Signed informed consent
* Age greater than or equal to 50 years

Exclusion Criteria

* Pigment epithelial detachment greater than 50% of the total lesion size
* Previous treatment for ARMD in the study eye
* Previous intravitreal drug delivery in the study eye
* History of vitrectomy in the study eye
* Fibrosis or atrophy involving the center of the fovea in the study eye
* Neovascular membrane from any other concurrent retinal disease such as high myopia (SER \> -8D), histoplasmosis or other ocular inflammatory disease.
* Known history of glaucoma and on more than one topical medication
* History of glaucoma filtering surgery in the study eye
* History of corneal transplant in the study eye
* Patients with co-existing macular disease such as diabetic macular edema
* Active intraocular inflammation in the study eye
* History of allergy to fluorescein not amenable to treatment
* Inability to comply with study or follow up procedures
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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QLT Inc.

INDUSTRY

Sponsor Role collaborator

Bay Area Retina Associates

OTHER

Sponsor Role lead

Responsible Party

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Bay Area Retina Associates

Principal Investigators

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Subhransu K Ray, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Bay Area Retina Associates

Locations

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Bay Area Retina Associates

Castro Valley, California, United States

Site Status

Bay Area Retina Associates

Walnut Creek, California, United States

Site Status

Georgia Retina

Riverdale, Georgia, United States

Site Status

Retina Vitreous Associates

Toledo, Ohio, United States

Site Status

Countries

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United States

References

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Bressler NM, Arnold J, Benchaboune M, Blumenkranz MS, Fish GE, Gragoudas ES, Lewis H, Schmidt-Erfurth U, Slakter JS, Bressler SB, Manos K, Hao Y, Hayes L, Koester J, Reaves A, Strong HA; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in patients with age-related macular degeneration: additional information regarding baseline lesion composition's impact on vision outcomes-TAP report No. 3. Arch Ophthalmol. 2002 Nov;120(11):1443-54. doi: 10.1001/archopht.120.11.1443.

Reference Type BACKGROUND
PMID: 12427056 (View on PubMed)

VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group; D'Amico DJ, Masonson HN, Patel M, Adamis AP, Cunningham ET Jr, Guyer DR, Katz B. Pegaptanib sodium for neovascular age-related macular degeneration: two-year safety results of the two prospective, multicenter, controlled clinical trials. Ophthalmology. 2006 Jun;113(6):992-1001.e6. doi: 10.1016/j.ophtha.2006.02.027. Epub 2006 Apr 27.

Reference Type BACKGROUND
PMID: 16647134 (View on PubMed)

Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology. 2006 Mar;113(3):363-372.e5. doi: 10.1016/j.ophtha.2005.11.019. Epub 2006 Feb 3.

Reference Type BACKGROUND
PMID: 16458968 (View on PubMed)

Edelman JL, Lutz D, Castro MR. Corticosteroids inhibit VEGF-induced vascular leakage in a rabbit model of blood-retinal and blood-aqueous barrier breakdown. Exp Eye Res. 2005 Feb;80(2):249-58. doi: 10.1016/j.exer.2004.09.013.

Reference Type BACKGROUND
PMID: 15670803 (View on PubMed)

Spaide RF, Sorenson J, Maranan L. Photodynamic therapy with verteporfin combined with intravitreal injection of triamcinolone acetonide for choroidal neovascularization. Ophthalmology. 2005 Feb;112(2):301-4. doi: 10.1016/j.ophtha.2004.08.012.

Reference Type BACKGROUND
PMID: 15691567 (View on PubMed)

Shah GK, Stein JD, Sharma S, Sivalingam A, Benson WE, Regillo CD, Brown GC, Tasman W. Visual outcomes following the use of intravitreal steroids in the treatment of postoperative endophthalmitis. Ophthalmology. 2000 Mar;107(3):486-9. doi: 10.1016/s0161-6420(99)00139-6.

Reference Type BACKGROUND
PMID: 10711885 (View on PubMed)

Tamura H, Miyamoto K, Kiryu J, Miyahara S, Katsuta H, Hirose F, Musashi K, Yoshimura N. Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina. Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1440-4. doi: 10.1167/iovs.04-0905.

Reference Type BACKGROUND
PMID: 15790913 (View on PubMed)

Chalam KV, Malkani S, Shah VA. Intravitreal dexamethasone effectively reduces postoperative inflammation after vitreoretinal surgery. Ophthalmic Surg Lasers Imaging. 2003 May-Jun;34(3):188-92.

Reference Type BACKGROUND
PMID: 12757090 (View on PubMed)

Blankenship GW. Evaluation of a single intravitreal injection of dexamethasone phosphate in vitrectomy surgery for diabetic retinopathy complications. Graefes Arch Clin Exp Ophthalmol. 1991;229(1):62-5. doi: 10.1007/BF00172263.

Reference Type BACKGROUND
PMID: 2004725 (View on PubMed)

Schmidt-Erfurth U, Schlotzer-Schrehard U, Cursiefen C, Michels S, Beckendorf A, Naumann GO. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4473-80. doi: 10.1167/iovs.02-1115.

Reference Type BACKGROUND
PMID: 14507895 (View on PubMed)

Wenzel A, Grimm C, Seeliger MW, Jaissle G, Hafezi F, Kretschmer R, Zrenner E, Reme CE. Prevention of photoreceptor apoptosis by activation of the glucocorticoid receptor. Invest Ophthalmol Vis Sci. 2001 Jun;42(7):1653-9.

Reference Type BACKGROUND
PMID: 11381074 (View on PubMed)

Augustin AJ, Schmidt-Erfurth U. Verteporfin and intravitreal triamcinolone acetonide combination therapy for occult choroidal neovascularization in age-related macular degeneration. Am J Ophthalmol. 2006 Apr;141(4):638-45. doi: 10.1016/j.ajo.2005.11.058.

Reference Type BACKGROUND
PMID: 16564797 (View on PubMed)

Nicolo M, Ghiglione D, Lai S, Nasciuti F, Cicinelli S, Calabria G. Occult with no classic choroidal neovascularization secondary to age-related macular degeneration treated by intravitreal triamcinolone and photodynamic therapy with verteporfin. Retina. 2006 Jan;26(1):58-64. doi: 10.1097/00006982-200601000-00010.

Reference Type BACKGROUND
PMID: 16395140 (View on PubMed)

Spaide RF, Laud K, Fine HF, Klancnik JM Jr, Meyerle CB, Yannuzzi LA, Sorenson J, Slakter J, Fisher YL, Cooney MJ. Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina. 2006 Apr;26(4):383-90. doi: 10.1097/01.iae.0000238561.99283.0e.

Reference Type BACKGROUND
PMID: 16603955 (View on PubMed)

Maturi RK, Bleau LA, Wilson DL. Electrophysiologic findings after intravitreal bevacizumab (Avastin) treatment. Retina. 2006 Mar;26(3):270-4. doi: 10.1097/00006982-200603000-00003.

Reference Type BACKGROUND
PMID: 16508425 (View on PubMed)

Manzano RP, Peyman GA, Khan P, Kivilcim M. Testing intravitreal toxicity of bevacizumab (Avastin). Retina. 2006 Mar;26(3):257-61. doi: 10.1097/00006982-200603000-00001.

Reference Type BACKGROUND
PMID: 16508423 (View on PubMed)

Related Links

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http://www.bayarearetina.com

Study Sponsor website

Other Identifiers

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PDEX

Identifier Type: -

Identifier Source: org_study_id

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