Combination Therapy for Age-Related Macular Degeneration.

Sponsor

Lawson Health Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00376701

Collaborator

QLT Inc. (Industry), Canadian Retinal Trials Group (Other)

103

Enrollment

Locations

Arms

Duration (Months)

20.6

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Age Related Macular Degeneration	Drug: Avastin (Bevacizumab) Drug: Bevacizumab Drug: Bevacizumab Drug: Bevacizumab	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

103 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Combination Therapy in Neovascular Age-Related Macular Degeneration (AMD): A Three-armed, Randomized, Prospective Clinical Trial of Low Fluence Photodynamic Therapy(rPDT) With Adjunctive Avastin and Triamcinolone Acetonide (Kenalog)(Triple Therapy) Versus rPDT With Adjunctive Avastin (Double Therapy) Versus Monotherapy With Avastin.

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Apr 1, 2009

Actual Study Completion Date :

Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Reduced fluence PDT plus intravitreal Kenalog (2 mg) plus intravitreal Avastin 1.25 mg	Drug: Avastin (Bevacizumab) Avastin 1.25 mg intravitreal Drug: Bevacizumab Intravitreal 1.25 mg Other Names: Avastin
Experimental: 2 Reduced fluence PDT plus intravitreal Avastin	Drug: Avastin (Bevacizumab) Avastin 1.25 mg intravitreal Drug: Bevacizumab Intravitreal 1.25 mg Other Names: Avastin
Experimental: 3 Intravitreal Avastin and sham reduced fluence PDT	Drug: Avastin (Bevacizumab) Avastin 1.25 mg intravitreal Drug: Bevacizumab Intravitreal Avastin 1.25 mg and sham reduced fluence PDT Other Names: Avastin

Arm

Intervention/Treatment

Experimental: 1

Reduced fluence PDT plus intravitreal Kenalog (2 mg) plus intravitreal Avastin 1.25 mg

Drug: Avastin (Bevacizumab)

Avastin 1.25 mg intravitreal

Drug: Bevacizumab

Intravitreal 1.25 mg

Other Names:

Avastin

Experimental: 2

Reduced fluence PDT plus intravitreal Avastin

Drug: Avastin (Bevacizumab)

Avastin 1.25 mg intravitreal

Drug: Bevacizumab

Intravitreal 1.25 mg

Other Names:

Avastin

Experimental: 3

Intravitreal Avastin and sham reduced fluence PDT

Drug: Avastin (Bevacizumab)

Avastin 1.25 mg intravitreal

Drug: Bevacizumab

Intravitreal Avastin 1.25 mg and sham reduced fluence PDT

Other Names:

Avastin

Outcome Measures

Primary Outcome Measures

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

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 c [1 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Choroidal neovascularization (CNV) secondary to age-related macular. All lesion subtypes, based upon IVFA evaluation will be included.
CNV under the geometric centre of the foveal avascular zone.
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.
Greatest linear dimension of the lesion </= 5400 um.
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.
Willingness and ability to participate and provide written informed consent

Exclusion Criteria:

Individuals with choroidal neovascularization from causes other than AMD.
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.)
Any intraocular surgery within 3 months in the study eye.
Prior retinal or vitreous surgery including posterior segment vitrectomy or scleral buckling in the study eye.
Any significant ocular disease that has compromised or could compromise vision in the study eye and confound analysis of the primary outcome.
Individuals with physical or mental disabilities that prevent accurate vision testing.
History of treatment of CNV in study eye other than extrafoveal confluent laser photocoagulation.
Prior photodynamic therapy for CNV in the study eye.
Active hepatitis or clinically significant liver disease
Any patient with recent history of new onset cardiac disease or thromboembolic CNS event in the past.
Subjects who are in an experimental therapy study or who have received experimental therapy within the last 12 weeks.
Subjects who are a poor medical risk because of other systemic diseases or active uncontrolled infections.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Alberta and Capital Health	Edmonton	Alberta	Canada	T5H 3V9
2	The University of British Columbia	Vancouver	British Columbia	Canada	V5Z 3N9
3	Dr. Stanley G. Shortt	Victoria	British Columbia	Canada	V8V 4X3
4	Ivey Eye Institute, St. Joseph's Health Care Centre	London	Ontario	Canada	N6A 4G5
5	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4M 3M5