The Pharmacokinetics of Topical Levofloxacin 1.5% vs Topical Moxifloxacin 0.5%
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 128
- 试验地点
- 2
- 主要终点
- Comparison of volume of distribution (Maximum Plasma Concentration) of Levofloxacin 1.5% vs Moxifloxacin 0.5% in the aqueous and vitreous fluid.
研究概览
简要总结
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 post-cataract surgery, this includes the use of pre-operative topical levofloxacin, intracameral cefuroxime, and providone iodine as ocular surface preparation.The proposed study is to evaluate the pharmacokinetic parameters of Levofloxacin 1.5% vs Moxifloxacin 0.5% aqueous and vitreous fluid after topical administration on the anterior segment parameters.
详细描述
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.
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.
Samples of aqueous (0.1 ml), and vitreous (0.2 ml) humour were taken simultaneously from the same patient at the commencement of surgery by paracentesis using a 30-gauge needle on a tuberculin syringe. All samples will be stored at -80°C as soon as possible until the concentrations of the drug will be measured.
Measurements for moxifloxacin and levofloxacin concentrations in aqueous fluid will be determined using HPLC with UV detection, which is currently undergoing method development and validation at the Faculty of Pharmacy, UKM. Measurements for moxifloxacin and levofloxacin concentrations in vitreous fluid will be outsourced to a laboratory at the Centre for Research and Instrument Management (CRIM) in UKM, due to the high sensitivity required to determine the drugs' concentrations in vitreous fluid.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients planned for vitrectomy for macula hole , ERM, RD surgery
- •Age 18 and above
- •Not on any topical medication
排除标准
- •Patients with underlying ocular surface disease
- •Fluoroquinolone allergy
研究组 & 干预措施
Levofloxacin -1 hour group
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.
干预措施: Levofloxacin Ophthalmic Solution (Drug)
Levofloxacin-2 hour group
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.
干预措施: Levofloxacin Ophthalmic Solution (Drug)
Levofloxacin-4 hour group
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.
干预措施: Levofloxacin Ophthalmic Solution (Drug)
Levofloxacin-6 hour group
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
干预措施: Levofloxacin Ophthalmic Solution (Drug)
Moxifloxacin-1 hour group
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.
干预措施: Moxifloxacin Ophthalmic Solution (Drug)
Moxifloxacin-2 hour group
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.
干预措施: Moxifloxacin Ophthalmic Solution (Drug)
Moxifloxacin-4 hour group
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.
干预措施: Moxifloxacin Ophthalmic Solution (Drug)
Moxifloxacin-6 hour group
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 6-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection.
干预措施: Moxifloxacin Ophthalmic Solution (Drug)
结局指标
主要结局
Comparison of volume of distribution (Maximum Plasma Concentration) of Levofloxacin 1.5% vs Moxifloxacin 0.5% in the aqueous and vitreous fluid.
时间窗: Throughout study completion, an average of 2 years
A compartmental analysis will be carried out. Data for the pooled aqueous and vitreous humor concentrations in each of the treatment groups, n, mean, SD, median, and coefficient of variation, and range values for each time point will be calculated. Since each patient contributed to this pooled non-compartmental analysis at a specified time point, Maximum Plasma Concentration (Cmax), and time to Cmax (Tmax) will be determined by direct observation.
Comparison of volume of distribution (Area under the plasma concentration versus time curve) of Levofloxacin 1.5% vs Moxifloxacin 0.5% in the aqueous and vitreous fluid.
时间窗: Throughout study completion, an average of 2 years
A compartmental analysis will be carried out. Data for the pooled aqueous and vitreous humor concentrations in each of the treatment groups, n, mean, SD, median, and coefficient of variation, and range values for each time point will be calculated. Since each patient contributed to this pooled non-compartmental analysis at a specified time point, a representative Area under the plasma concentration versus time curve (AUC0-6) will be determined by direct observation. The median AUC0-6 calculation will be performed using the linear trapezoid method.
Comparison of concentration of Levofloxacin 1.5% and Moxifloxacin 0.5% in the aqueous and vitreous fluid.
时间窗: Throughout study completion, an average of 2 years
The mean concentration vs time of last drop (i.e. AUC) will be plotted for both levofloxacin 1.5% and moxofloxacin 0.5% in aqueous and vitreous fluids. A Kruskal-Wallis non-parametric one-way analysis of variance (ANOVA) will be used to detect differences between the concentrations in each treatment arm at various time points.
次要结局
未报告次要终点
研究者
Wan Haslina Wan Abdul Halim
Consultant Ophthalmologist-Cornea And Anterior Segment
National University of Malaysia