Alprostadil in Maculopathy Study (AIMS)

Study Overview
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Brief Summary
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Evaluation of efficacy of alprostadil (prostaglandin E1) for treatment of patients suffering from dry age-related macula degeneration

Detailed Description
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Results of the planned interim analysis indicated that the number of originally planned patients were not sufficient to reach statistical significance in the primary end point. Instead of increasing the sample size accordingly, it was decided to terminate the study and plan future proceedings based on a careful analysis of the unblinded results.

Official Title
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Confirmatory, Prospective, Randomized, Double-blind, Placebo-controlled, Parallel Groups Study to Assess the Efficacy and Safety of Prostaglandin E1 in Subjects With Dry Age-related Macular Degeneration.

Conditions
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Macular Degeneration

Intervention / Treatment
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* Drug: Alprostadil (prostaglandin E1)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects older than 50 years of age. Dry age-related macula degeneration (AMD) with hard drusen and possibly beginning geographic atrophy in one eye Visual acuity between 0.2 and 0.7 (logMAR) assessed with ETDRS charts Exclusion Criteria: Dry AMD AREDS category 3 or 4 in both eyes Wet AMD in at least one eye Detachment of the pigmentary epithelium Glaucoma Diabetic retinopathy Medical history of retinal vein occlusion Uveitis Cataract surgery during the study High myopia (< -6 dpt) with pathological findings of the retina Medical history of any opthalmic surgery with complications Medical history of cataract surgery without complications within the last 12 weeks Medical history of vitrectomy AREDS medication within the last 2 days Opthalmologic dietary supplements within the last 2 days Medical history of retinal hemorrhage Cardiac failure (NYHA grade II or higher) Inadequately controlled coronary heart disease or cardiac arrhythmia Subject has a medical history and/or suspicion of pulmonary edema or pulmonary infiltration Subject has a peripheral edema Myocardial infarction within 6 months prior to enrollment Subject has renal insufficiency, compensated retention (creatinine > 1,5 mg/dL) Subject has known existing malignant disease Severe chronic obstructive pulmonary disease Subject has a venoocclusive lung disease Known hepatic disease Inadequately controlled or untreated hypertension (systolic blood pressure ≥ 180 mmHg, diastolic blood pressure ≥ 110 mmHg) Subject has upper grade cardiac valvular disorders Pregnancy or lactation period Known hypersensitivity to PGE1 or to any component of the trial medication Subject has a history of chronic alcohol or drug abuse within the past 2 years Subject has known lactose intolerance Poor general state of health or other criteria Subject has other serious illness Laboratory values outside the normal range unless considered not clinically relevant by the investigator

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alprostadil<br>Alprostadil | Drug: Alprostadil (prostaglandin E1)<br>* Alprostadil 20 µg ampoules; 60 µg alprostadil/d i.v. for 15 days.<br>* Other names: Prostavasin;|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Placebo/d i.v. for 15 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Visual Acuity Between Measurements at 3 Months After Drug Intervention and Measurements at Baseline (Assessed Within Early Treatment Diabetic Retinopathy Study (ETDRS) Chart) | Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly. | From baseline to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Difference in Visual Acuity Between Measurements Immediately After Intervention and Measurements at Baseline | Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly. | From baseline to time immediately after intervention | 
| The Difference in Visual Acuity Between Measurements at 6 Months After Intervention and Measurements at Baseline | Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly. | From baseline to 6 months | 
| Progression of the Dry Age-related Macular Degeneration | Severity of the diagnosed dry age-related macular degeneration (AMD) was assessed in comparison to Baseline and classified as Progression Stabilization Amelioration | From baseline to 6 months | 
| Development of a Wet Age-related Macular Degeneration | A wet age-related macular degeneration (AMD) is defined as the development of choroidal neovascularization of the study-eye (worse eye). Development is categorized in Yes and No, where Yes means that a subject who had no wet AMD at Screening has developed a wet AMD at Week 29. | From baseline to 6 months | 
| The Difference in Contrast Sensitivity Between Measurements Immediately After Intervention and Measurements at Baseline | Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability. | From baseline to time immediately after intervention | 
| The Difference in Contrast Sensitivity Between Measurements at 3 Months After Intervention and Measurements at Baseline | Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability. | From baseline to 3 months | 
| The Difference in Contrast Sensitivity Between Measurements at 6 Months After Intervention and Measurements at Baseline | Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability. | From baseline to 6 months | 
| The Difference in Color Vision Between Measurements Immediately After Intervention and Measurements at Baseline | The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'. | From baseline to time immediately after intervention | 
| The Difference in Color Vision Between Measurements at 3 Months After Intervention and Measurements at Baseline | The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'. | From baseline to 3 months | 
| The Difference in Color Vision Between Measurements at 6 Months After Intervention and Measurements at Baseline | The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'. | From baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alprostadil, prostaglandin E1, Prostavasin®, macular degeneration