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Combination Therapy for Age-Related Macular Degeneration.

Phase 2
Completed
Conditions
Age Related Macular Degeneration
Interventions
Registration Number
NCT00376701
Lead Sponsor
Lawson Health Research Institute
Brief Summary

The primary purpose of the study is to investigate whether patients with Choroidal Neovascularization secondary to Age-related Macular Degeneration, receiving triple or double therapy compared to monotherapy with Avastin will reduce the intervention rate with equivalent safety and efficacy.

Detailed Description

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries throughout the world.The beneficial therapeutic effect of Photodynamic Therapy (PDT)in the treatment of AMD is modest. The treatment benefit of PDT may be moderated by PDT-induced, non-selective effects in the choroidal circulation (resulting in hypoxia-induced stimulation of angiogenesis through increased vascular endothelial growth factor (VEGF)production), direct injury to the retinal pigment epithelium, and subretinal fluid/hemorrhage or post-treatment inflammation secondary to PDT. There is potential that supplemental Avastin (through VEGF inhibition) or intravitreal Triamcinolone Acetonide (ITA) treatments (through non-specific membrane stabilizing, anti-neovascular, and anti-inflammatory activities) could minimize the effect of these processes, enhancing the efficacy of PDT. Presently, PDT, the current gold standard,in combination with Avastin and/or Kenalog is being more widely used in exactly this fashion and may become the standard of care without the necessary randomized clinical trial. However, the treatment benefit of these interventions is uncertain as is their safety profile.

This randomized, controlled trial addresses the potential supplemental therapeutic effect of intravitreal injection of Triamcinolone Acetonide and/or Avastin in conjunction with photodynamic therapy for the treatment of sub-foveal CNVM secondary to AMD.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
103
Inclusion Criteria
  1. Choroidal neovascularization (CNV) secondary to age-related macular. All lesion subtypes, based upon IVFA evaluation will be included.
  2. CNV under the geometric centre of the foveal avascular zone.
  3. Evidence of choroidal neovascular activity as suggested by one of the following: sub-retinal lipid, sub-retinal hemorrhage, and documented loss of 3 lines of vision within the last three months.
  4. Greatest linear dimension of the lesion </= 5400 um.
  5. Visual acuity of between 20/32 and 20/800 in the study eye - Equivalent to Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart score of 5 to 75 letters at 2 metres.
  6. Willingness and ability to participate and provide written informed consent
Exclusion Criteria
  1. Individuals with choroidal neovascularization from causes other than AMD.
  2. Individuals physically unable to tolerate intravenous fluorescein angiography or Verteporfin injections. (Specifically, individuals with inadequate venous access or an allergy/sensitivity to fluorescein dye/porphyrins will be excluded.)
  3. Any intraocular surgery within 3 months in the study eye.
  4. Prior retinal or vitreous surgery including posterior segment vitrectomy or scleral buckling in the study eye.
  5. Any significant ocular disease that has compromised or could compromise vision in the study eye and confound analysis of the primary outcome.
  6. Individuals with physical or mental disabilities that prevent accurate vision testing.
  7. History of treatment of CNV in study eye other than extrafoveal confluent laser photocoagulation.
  8. Prior photodynamic therapy for CNV in the study eye.
  9. Active hepatitis or clinically significant liver disease
  10. Any patient with recent history of new onset cardiac disease or thromboembolic CNS event in the past.
  11. Subjects who are in an experimental therapy study or who have received experimental therapy within the last 12 weeks.
  12. Subjects who are a poor medical risk because of other systemic diseases or active uncontrolled infections.
  13. Women of child-bearing potential who are not on two forms of effective contraception during the trial and for at least 60 days following the last dose of study medications.

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
1Avastin (Bevacizumab)Reduced fluence PDT plus intravitreal Kenalog (2 mg) plus intravitreal Avastin 1.25 mg
1BevacizumabReduced fluence PDT plus intravitreal Kenalog (2 mg) plus intravitreal Avastin 1.25 mg
2Avastin (Bevacizumab)Reduced fluence PDT plus intravitreal Avastin
3Avastin (Bevacizumab)Intravitreal Avastin and sham reduced fluence PDT
3BevacizumabIntravitreal Avastin and sham reduced fluence PDT
2BevacizumabReduced fluence PDT plus intravitreal Avastin
Primary Outcome Measures
NameTimeMethod
To investigate whether patients with CNV secondary to AMD, receiving triple or double therapy compared to monotherapy with Avastin, will reduce the intervention rate with equivalent safety and efficacy.1 year
Secondary Outcome Measures
NameTimeMethod
To compare between treatment groups:1 year
Whether combination therapy with rPDT + iA and rPDT + iAK in patients with sub-foveal CNVM of all types secondary to ARMD will result in a significant improvement in visual acuity defined as 2 or more lines (10+ letters) on a standardized ETDRS chart c1 year
Lesion growth and activity over the study period.1 year
Contrast sensitivity.1 year
The rate of cataract progression.1 year
Central retinal thickness via Optical Coherence Tomography (OCT).1 year

Trial Locations

Locations (5)

The University of British Columbia

🇨🇦

Vancouver, British Columbia, Canada

The University of Alberta and Capital Health

🇨🇦

Edmonton, Alberta, Canada

Dr. Stanley G. Shortt

🇨🇦

Victoria, British Columbia, Canada

Ivey Eye Institute, St. Joseph's Health Care Centre

🇨🇦

London, Ontario, Canada

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

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