The Sahlgrenska Anti-VEGF Study

Study Overview
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Brief Summary
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The study investigates whether patients treated for neovascular (wet) age-related macular degeneration (AMD), with intravitreal injection with bevacizumab (Avastin) after two years need more injections with retained therapy response compared to patients being treated with intravitreal injection with aflibercept (Eylea). The study also aims to evaluate if there is a difference in best-corrected visual acuity, macular thickness, recurrence interval, durability, cost efficiency, as well as vision-related quality of life.

Official Title
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The Sahlgrenska Anti-VEGF (SAHLVE) Study - a Prospective Randomized Double-blind Comparison of Bevacizumab and Aflibercept in Patients With Neovascular Age-related Macular Degeneration

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Bevacizumab Injection
* Drug: Aflibercept Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. ≥50 years, regardless of gender. Diagnosed with the neovascular (wet) form of age-related macular degeneration through diagnosed neovascular vascular membranes with OCT-A and, if necessary, also FA / ICG, according to clinical routine. Distance visual acuity ≥34 (ETDRS) on the current study eye. Exclusion Criteria: Other eye disease in the current study eye that affects visual acuity or the possibility of examining fundus, according to the investigator's assessment. Previously received treatment for the neovascular (wet) form of age-related macular degeneration. Diagnosed with diabetes (all types). Degenerative state of the macula that prevents vision improvement such as central areolar atrophy or other pronounced dry AMD or fibrosis, in the current study eye. Other choroidal neovascularization (CNV) of the type PCV or due to grave myopia i.e. ≥ 6.0 diopters (D) or secondary to other retinal disease, in the current study eye. Unregulated intraocular pressure (IOP) > 30 mmHg despite pharmacological treatment in the current study eye. Have had a stroke or heart attack ≤6 months ago. Inability to access information (e.g. due to dementia) or inability to conduct examinations (e.g. ETDRS examination), according to the investigator's assessment. Inability to receive oral and written information in Swedish (in need of an interpreter). Included in another intervention study. Fertile woman i.e. a woman who has had menstruation for the past 12 months or has not undergone permanent sterilization (hysterectomy, bilateral salpingectomy or bilateral oophorectomy).

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, controlled, randomized, double-blind
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avastin<br>bevacizumab 25 mg/ml, intravitreal administration, 0.05 ml (1.25 mg) | Drug: Bevacizumab Injection<br>* 25 mg/ml<br>* Other names: Avastin;|
| Active Comparator: Eylea<br>aflibercept 40 mg/ml, intravitreal administration, 0.05 ml (2 mg) | Drug: Aflibercept Injection<br>* 40 mg/ml<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of injections | Number of intravitreal injections | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best-corrected visual acuity (BCVA), distance | ETDRS | Two years | 
| Best-corrected visual acuity (BCVA), near | LIX | Two years | 
| Macular thickness (Central Retinal Thickness; CRT) | μm | Two years | 
| Intraocular pressure (IOP) | mmHg | Two years | 
| Recurrence interval | Maximum number of weeks from last injection to relapse, at first and last relapse. | Two years | 
| Durability | Longest inactive interval detected (number of weeks). | Two years | 
| Cost efficiency | Quality-adjusted life years (QALY), cost-per-QALY is measured with the EuroQol-5 Dimension (EQ-5D) questionnaire. EQ-5D consists of five subscales: mobility, self-care, usual activities, discomfort/pain and anxiety/depression. The subscales measure different aspects of health and well-being where the subject is asked to rank each subscale from 1 (no problems) to 3 (major problems). These answers are converted to a score between 0 (=death) to 1 (=full health). The subscales are converted to a weighted mean which ranges from 0 (death) to 1 (full health). Negative values may exists for conditions worse than death. The weighting differs between geographic areas; for Sweden, the UK weighting scale is used. | Two years | 
| Vision-related quality of life | National Eye Institute Visual Functioning Questionnaire -25 (NEI VFQ-25) questionnaire is based on 25 questions (items) where the subject is asked questions on visual function, daily activities and social consequences of visual function. The questions have answers on a 5- or 6-grade scale which are converted to a scale from 0 (no function/worst consequence) to 100 (no problems). The 25 items are clustered into 12 subscales. Items within each subscale are averaged to create the subscale scores according to the NEI VFQ-25 scoring algorithm. In addition, a composite score for all 12 subscales are created as an average of these. Minimum score is 0 and maximum score is 100 for each item, subscale and the composite score. | Two years | 
| Cost-benefit | The incremental cost-effectiveness ratio (ICER) is a statistic used in cost-effectiveness analysis to summarise the cost-effectiveness of a health care intervention. It represents the average incremental cost associated with 1 additional unit of the measure of effect and is given in Euro. | Two years |