Combination Therapy for Age-Related Macular Degeneration. - Full Text View

Sponsors and Collaborators:	Lawson Health Research Institute QLT Inc Canadian Retinal Trials Group
Information provided by:	Lawson Health Research Institute
ClinicalTrials.gov Identifier:	NCT00376701

Purpose

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	Intervention	Phase
Age Related Macular Degeneration	Drug: Avastin (Bevacizumab) Drug: Bevacizumab	Phase II

Genetics Home Reference related topics: X-linked juvenile retinoschisis

MedlinePlus related topics: Macular Degeneration

Drug Information available for: Bevacizumab Triamcinolone acetonide Triamcinolone Triamcinolone diacetate Triamcinolone hexacetonide Verteporfin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Factorial Assignment, Safety/Efficacy Study
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.

Further study details as provided by Lawson Health Research Institute:

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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To compare between treatment groups: [ Time Frame: 1 year ] [ Designated as safety issue: No ]
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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Lesion growth and activity over the study period. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Contrast sensitivity. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
The rate of cataract progression. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Central retinal thickness via Optical Coherence Tomography (OCT). [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment:	106
Study Start Date:	September 2006
Estimated Study Completion Date:	April 2009
Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Reduced fluence PDT plus intravitreal Kenalog (2 mg) plus intravitreal Avastin 1.25 mg	Drug: Avastin (Bevacizumab) Avastin 1.25 mg intravitreal Drug: Bevacizumab Intrarvitreal 1.25 mg
2: Experimental Reduced fluence PDT plus intravitreal Avastin	Drug: Avastin (Bevacizumab) Avastin 1.25 mg intravitreal Drug: Bevacizumab Intravitreal 1.25 mg
3: Experimental 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

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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376701

Locations

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

Sponsors and Collaborators

Lawson Health Research Institute

QLT Inc

Canadian Retinal Trials Group

Investigators

Principal Investigator:

Thomas G. Sheidow, MD

University of Western Ontario, Canada

More Information

Responsible Party:	Ivey Eye Institute, London, Ontario, Canada ( DR. Tom Sheidow )
Study ID Numbers:	R-06-441, Health Canada Control #106990, 9427-U0207/2-21C
Study First Received:	September 14, 2006
Last Updated:	August 14, 2008
ClinicalTrials.gov Identifier:	NCT00376701
Health Authority:	Canada: Health Canada

Keywords provided by Lawson Health Research Institute:

Choroidal Neovascularization
Photodynamic Therapy
Age Related Macular Degeneration

Triamcinolone Acetonide
Avastin
Visudyne

Study placed in the following topic categories:

Eye Diseases
Verteporfin
Macular Degeneration
Retinal Degeneration
Triamcinolone diacetate
Bevacizumab
Choroidal Neovascularization

Triamcinolone hexacetonide
Triamcinolone Acetonide
Triamcinolone
Neovascularization, Pathologic
Retinal Diseases
Retinal degeneration

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Enzyme Inhibitors

Glucocorticoids
Hormones
Immunosuppressive Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on January 15, 2009