Assessment of the Mu-Drop System for Serum Eye Drops

Study Overview
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Brief Summary
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Rationale: Serum eye drops (SEDs) are used to treat patients with severe signs and symptoms of dry eyes and other corneal defects. Serum is used in severe ophthalmic cases where conventional treatment and/or eye drops (artificial tears) have insufficient effect. The use of SEDs in dry eye patients usually has a rapid effect. Most patients claim the effect to be instantaneous, and most symptoms improve within 48-72 hours. There is evidence suggesting that substances in serum may help in the healing of epithelial defects, such as epidermal growth factor, fibroblast growth factor, fibronectin, and/or vitamin A. However, the precise serum factor responsible for alleviating the patient's complaints is currently not known. SEDs are considered as a blood product under EU blood legislation (Directive 2002/98/EC), as well as in New Zealand and Australia. Commonly, autologous SEDs are used, but they are replaced more and more by allogeneic SEDs prepared from donor serum. Allogeneic SEDs are derived from healthy voluntary, non-remunerated male donors with blood group AB, and have the benefit of blood bank controlled quality. They can be delivered from stock and are therefore quickly available for each patient. For application of eye drops, generally administration systems with a drop size of 40 to 50 µl are used, further on referred to as conventional sized eye drops. From previous studies done with medicinal eye drops, it has been shown that smaller eye drops, so called micro drops, can be just as effective and sometimes even superior to conventional drops for treatment of eye disease. If micro drops are just as effective or maybe even superior to conventional sized eye drops is currently unknown for the use of SEDs. This study will compare the feasibility and effectiveness of allogeneic serum micro eye drops using the mu-Drop applicator to the conventional sized allogeneic eye drops using the Meise applicator. Both systems have a closed manufacturing system. Objective: The main objective is to determine whether the administration of allogeneic serum micro eye drops is non-inferior in terms of effectiveness and safety as compared to the conventional sized drops. Main study parameters/endpoints: The primary endpoint is the improvement in OSDI score by using SEDs (OSDI score after treatment minus OSDI score before treatment), independent of the drop size, showing non-inferiority for the use of micro drops as compared to conventional sized drops.

Official Title
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Allogenic Serum Micro Eye Drops Compared to Conventional Sized Eye Drops: A Prospective Randomized Non-inferiority, Investigator Masked, Cross-over Multicenter Clinical Study

Conditions
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Dry Eye Syndrome

Intervention / Treatment
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* Other: Allogeneic conventional sized serum eye drops
* Other: Allogeneic micro sized serum eye drops


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with severe signs and symptoms of dry eyes. Age 16 years or older. Punctate staining of the cornea. Expected to benefit from SEDs. Not previously treated with SEDs. Exclusion Criteria: Actively or previously treated for Herpes Simplex Virus (HSV) keratitis. Corneal lesions, more than punctate. Untreated Meibomian gland disease. Pregnant or lactating or intending to become pregnant in the next 3 months Unable or unwilling to give informed consent. Active (systemic) microbial infection. The use of all types of contact lenses. Discontinuous use of medication that affects the dry eye sensation is not allowed (e.g. discontinuous use of local corticosteroids). Continuous use of co-medication, like lubricants, anti-glaucoma eye drops or other drops, that have to be used on a daily basis are allowed, and are expected to be used throughout the study period in both eyes (continuous use of the same medication is allowed if used at least one month prior to start of the study).

Ages Eligible for Study
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Minimum Age: 16 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic conventional sized serum eye drops<br> | Other: Allogeneic conventional sized serum eye drops<br>* allogeneic serum conventional sized drops (40-50 µL, administrated using the Meise applicator) applied six times a day (when appropriate, lowering the dose to 3-4 times a day is allowed) for a period of one month<br>Other: Allogeneic micro sized serum eye drops<br>* Allogeneic serum micro eye drops (5-10 µL, administrated using the mu-Drop applicator) applied six times a day (when appropriate, lowering the dose to 3-4 times a day is allowed) for a period of one month<br>|
| Experimental: Allogeneic micro sized serum eye drops<br> | Other: Allogeneic conventional sized serum eye drops<br>* allogeneic serum conventional sized drops (40-50 µL, administrated using the Meise applicator) applied six times a day (when appropriate, lowering the dose to 3-4 times a day is allowed) for a period of one month<br>Other: Allogeneic micro sized serum eye drops<br>* Allogeneic serum micro eye drops (5-10 µL, administrated using the mu-Drop applicator) applied six times a day (when appropriate, lowering the dose to 3-4 times a day is allowed) for a period of one month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Surface Disease Index (OSDI index) | The primary endpoint is the improvement in OSDI score by using SEDs (OSDI score after treatment minus OSDI score before treatment), independent of the drop size, showing non-inferiority for the use of micro drops as compared to conventional sized drops. The OSDI score falls between 0 and 100, ranging from normal, mild, moderate to severe dry eyes. | One month after starting the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Schirmer's test | Tear production in mm | One month after starting the intervention | 
| Tear break up time | number of seconds the dry spot appears in the ter film | One month after starting the intervention | 
| Corneal punctates | Percentage of affected surface after staining of the cornea | One month after starting the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allogeneic serum eye drops, Micro eye drops, Cross-over multicenter trial, Ocular Surface Disease Index (OSDI)