The Clinical Safety of Levofloxacin 1.5% vs Topical Moxifloxacin 0.5%

Study Overview
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Brief Summary
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Endophthalmitis is defined as intraocular inflammatory disorder affecting the vitreous cavity that can result from exogenous or endogenous spread of infecting organisms into the eye. Patients presents with reduced or blurred vision, red eye, pain, and lid swelling. Endophthalmitis can progress into panophthalmitis, corneal infiltration and perforation, and finally phthisis bulbi. For exogenous endopthalmitis, the intraocular inflammation occurs due to a breach of the ocular compartment. The infectious agent indirectly introduced into the eye. This usually happens after intraocular surgery such as cataract surgery, vitrectomy, glaucoma filtration surgery, intravitreal injections, and other causes include penetrating ocular trauma or from adjacent periocular tissue. Several prophylactic measures have been taken to reduce the incidence of post-operative endopthalmitis postcataract surgery, this includes the use of pre-operative topical levofloxacin, intrameral cefuroxime, and providone iodine as ocular surface preparation.The proposed study is to evaluate clinical safety of Levofloxacin 1.5% and Moxifloxacin 0.5% on the anterior segment parameters.

Detailed Description
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This is a prospective, double - blinded randomized clinical trial conducted in University Kebangsaan Malaysia Medical Centre (UKMMC) where there are two intervention arms. All patients from Ophthalmology Clinic in UKM Medical Centre from September 2019 till December 2021 will be involved in this study. Patients who fulfill the inclusion criteria will be included in this study. All eligible subjects will be asked to sign an informed consent. The qualified patients will be randomized on a 1:1 ratio into each treatment arm. Qualified eyes were further randomized into one of four subgroups, which specified the time between the last drop of study medication and the time of aqueous and vitreous humor sample collection (i.e., 1-, 2-, 4-, and 6-hour subgroups- about 32 patients per subgroup-: 16 Levofloxacin, 16 Moxifloxacin. Patient will undergo clinical assessment at the outpatient Ophthalmology Clinic at UKMMC. Initially, a non-contact assessment of the corneal surface will be done by the Keratograph 5. The parameters recorded are non-invasive tear break up time (NITBUT), tear film properties and redness analysis. The endothelial cell count will be analysed with a specular microscopy. Subsequently, patient will be assessed by a blinded ophthalmologist for clinical evaluation of corneal surface which includes tear break up time (TBUT), ocular surface abnormality and Rose-bengal staining. During the first visit, each patient will be educated on proper instillation of the eye drops to ensure the proper dose is administered. A prior observation of self- instillation of the eye drop by the study staff is required. For 3 days prior to the day of the elective vitrectomy surgery, subjects will instill exactly one drop of study medication into their operative eye four times daily. On the day of surgery (visit 2, day 4), patients will receive their final drop of study medication administered by trained study personnel at the study site. Post-vitrectomy, patients will be continued on the specified antibiotics for 4 hourly for 2 weeks. Then the antibiotic will taper down to 6 hourly (QID) daily for 1 week and antibiotics will be discontinued after that. Corneal safety will be assessed at 1 week and 4 weeks post operatively.

Official Title
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The Clinical Safety of Topical Levofloxacin 1.5% vs Topical Moxifloxacin 0.5%

Conditions
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Endophthalmitis Postoperative

Intervention / Treatment
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* Drug: Levofloxacin Ophthalmic Product
* Drug: Moxifloxacin Ophthalmic Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients planned for vitrectomy for macula hole, ERM, RD surgery Age 18 and above Not on any topical medication Exclusion Criteria: Patients with underlying ocular surface disease Fluoroquinolone allergy

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The qualified patients will be randomized on a 1:1 ratio into each treatment arm. Qualified eyes were further randomized into one of four subgroups, which specified the time between the last drop of study medication and the time of aqueous and vitreous humor sample collection (i.e., 1-, 2-, 4-, and 6-hour subgroups- about 32 patients per subgroup. Within each subgroups, there will be 16 of Levofloxacin group and 16 of Moxifloxacin group.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levofloxacin -1 hour group<br>Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 1-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection. | Drug: Levofloxacin Ophthalmic Product<br>* Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily for 3 days pre-operatively and one drop on the day of operation.<br>* Other names: Cravit 1.5%;|
| Active Comparator: Levofloxacin-2 hour group<br>Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 2-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection. | Drug: Levofloxacin Ophthalmic Product<br>* Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily for 3 days pre-operatively and one drop on the day of operation.<br>* Other names: Cravit 1.5%;|
| Active Comparator: Levofloxacin-4 hour group<br>Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 4-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection. | Drug: Levofloxacin Ophthalmic Product<br>* Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily for 3 days pre-operatively and one drop on the day of operation.<br>* Other names: Cravit 1.5%;|
| Active Comparator: Levofloxacin-6 hour group<br>Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 6-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection. | Drug: Levofloxacin Ophthalmic Product<br>* Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily for 3 days pre-operatively and one drop on the day of operation.<br>* Other names: Cravit 1.5%;|
| Active Comparator: Moxifloxacin-1 hour group<br>Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 1-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection. | Drug: Moxifloxacin Ophthalmic Solution<br>* Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily for 3 days pre-operatively and one drop on the day of operation.<br>* Other names: Vigamox 0.5%;|
| Active Comparator: Moxifloxacin-2 hour group<br>Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 2-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection. | Drug: Moxifloxacin Ophthalmic Solution<br>* Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily for 3 days pre-operatively and one drop on the day of operation.<br>* Other names: Vigamox 0.5%;|
| Active Comparator: Moxifloxacin-4 hour group<br>Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 4-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection. | Drug: Moxifloxacin Ophthalmic Solution<br>* Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily for 3 days pre-operatively and one drop on the day of operation.<br>* Other names: Vigamox 0.5%;|
| Active Comparator: Moxifloxacin-6 hour group<br>Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 8-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection. | Drug: Moxifloxacin Ophthalmic Solution<br>* Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily for 3 days pre-operatively and one drop on the day of operation.<br>* Other names: Vigamox 0.5%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of change in corneal surface in patients treated with topical levofloxacin 1.5% ophthalmic solution and topical moxifloxacin 0.5% ophthalmic solution | Evaluation of non-invasive tear break-up time (NITBUT), redness analysis, tear meniscus height and Tear Break-up Time (TBUT) of corneal surface from Baseline by using Oculus Keratograph-5 Machine at Day 3 of eyedrop instillation. Corneal surface signs (ie punctate epithelial erosions) is also measured by slit-lamp examination and graded using Oxford Scale Eye Grading. | Day 3 of eyedrop instillation | 
| Comparison of change in corneal surface in patients treated with topical levofloxacin 1.5% ophthalmic solution and topical moxifloxacin 0.5% ophthalmic solution. | Evaluation of non-invasive tear break-up time (NITBUT), redness analysis, tear meniscus height and Tear Break-up Time (TBUT) of corneal surface from Baseline by using Oculus Keratograph-5 Machine at 1-month post operation. Corneal surface signs (ie punctate epithelial erosions) is also measured by slit-lamp examination and graded using Oxford Scale Eye Grading. | 1-month post operation | 
| Comparison of Concentration of Endothelial cell count (cells/mm2) in patients treated with topical levofloxacin 1.5% ophthalmic solution and topical moxifloxacin 0.5% ophthalmic solution | Change in Concentration of Endothelial cell count (cells/mm2) from Baseline, measured at Day 3 of eyedrop instillation using a non-contact TOPCON Specular Microscopy model SP-1P. | Day 3 of eyedrop instillation | 
| Comparison of Concentration of Endothelial cell count (cells/mm2) in patients treated with topical levofloxacin 1.5% ophthalmic solution and topical moxifloxacin 0.5% ophthalmic solution | Change in Concentration of Endothelial cell count (cells/mm2) from Baseline, measured at 1-month post-operation using a non-contact TOPCON Specular Microscopy model SP-1P. | 1-month post-operation | 
| Comparison of Endothelial cell morphology in patients treated with topical levofloxacin 1.5% ophthalmic solution and topical moxifloxacin 0.5% ophthalmic solution | Change in Endothelial cell morphology from Baseline by assessing the Polymegathism (CV) which is the variation in individual cell areas, and Pleomorphism which is the increased in variability of cell shape, at Day 3 of eyedrop instillation using a non-contact TOPCON Specular Microscopy model SP-1P. | Day 3 of eyedrop instillation | 
| Comparison of Endothelial cell morphology in patients treated with topical levofloxacin 1.5% ophthalmic solution and topical moxifloxacin 0.5% ophthalmic solution | Change in Endothelial cell morphology from Baseline by assessing the Polymegathism (CV) which is the variation in individual cell areas, and Pleomorphism which is the increased in variability of cell shape, at 1-month post-operation using a non-contact TOPCON Specular Microscopy model SP-1P. | 1-month post-operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side effects | To report any untoward incidence of endophthalmitis during the study period. | Post-operative period until study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Safety, Levofloxacin 1.5%, Moxifloxacin 0.5%