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

Endophthalmitis Postoperative Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04212429
• Other study ID #: FF-2019-320
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 23, 2019
• Est. completion date: May 2022

Study information

• Verified date: December 2019
• Source: National University of Malaysia
• Contact: Wan Haslina Wan Abdul Halim, M.D(UKM)
• Phone: +6019-6679633
• Email: afifiyad[@]yahoo.co.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 128
• Est. completion date: May 2022
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endophthalmitis
• Endophthalmitis Postoperative

Intervention

Drug:
• Levofloxacin Ophthalmic Product
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.
• Moxifloxacin Ophthalmic Solution
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.

Locations

Country	Name	City	State
Malaysia	UKM Medical Centre	Cheras	Kuala Lumpur

Sponsors (2)

Lead Sponsor	Collaborator
National University of Malaysia	Santen Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

Malaysia, 

References & Publications (10)

Bucci FA Jr, Nguimfack IT, Fluet AT. Pharmacokinetics and aqueous humor penetration of levofloxacin 1.5% and moxifloxacin 0.5% in patients undergoing cataract surgery. Clin Ophthalmol. 2016 May 2;10:783-9. doi: 10.2147/OPTH.S91286. eCollection 2016. — View Citation

Hanscom TA. Postoperative endophthalmitis. Clin Infect Dis. 2004 Feb 15;38(4):542-6. Epub 2004 Jan 26. — View Citation

Hariprasad SM, Blinder KJ, Shah GK, Apte RS, Rosenblatt B, Holekamp NM, Thomas MA, Mieler WF, Chi J, Prince RA. Penetration pharmacokinetics of topically administered 0.5% moxifloxacin ophthalmic solution in human aqueous and vitreous. Arch Ophthalmol. 20 — View Citation

Jackson MA, Schutze GE; COMMITTEE ON INFECTIOUS DISEASES. The Use of Systemic and Topical Fluoroquinolones. Pediatrics. 2016 Nov;138(5). pii: e20162706. Review. — View Citation

Jackson TL, Paraskevopoulos T, Georgalas I. Systematic review of 342 cases of endogenous bacterial endophthalmitis. Surv Ophthalmol. 2014 Nov-Dec;59(6):627-35. doi: 10.1016/j.survophthal.2014.06.002. Epub 2014 Jun 18. Review. — View Citation

Kernt M, Kampik A. Endophthalmitis: Pathogenesis, clinical presentation, management, and perspectives. Clin Ophthalmol. 2010 Mar 24;4:121-35. — View Citation

Nishida T, Ishida K, Niwa Y, Kawakami H, Mochizuki K, Ohkusu K. An eleven-year retrospective study of endogenous bacterial endophthalmitis. J Ophthalmol. 2015;2015:261310. doi: 10.1155/2015/261310. Epub 2015 Jan 31. — View Citation

Puustjärvi T, Teräsvirta M, Nurmenniemi P, Lokkila J, Uusitalo H. Penetration of topically applied levofloxacin 0.5% and ofloxacin 0.3% into the vitreous of the non-inflamed human eye. Graefes Arch Clin Exp Ophthalmol. 2006 Dec;244(12):1633-7. — View Citation

Robertson SM, Curtis MA, Schlech BA, Rusinko A, Owen GR, Dembinska O, Liao J, Dahlin DC. Ocular pharmacokinetics of moxifloxacin after topical treatment of animals and humans. Surv Ophthalmol. 2005 Nov;50 Suppl 1:S32-45. Review. — View Citation

Watanabe R, Nakazawa T, Yokokura S, Kubota A, Kubota H, Nishida K. Fluoroquinolone antibacterial eye drops: effects on normal human corneal epithelium, stroma, and endothelium. Clin Ophthalmol. 2010 Oct 21;4:1181-7. doi: 10.2147/OPTH.S13672. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Side effects	To report any untoward incidence of endophthalmitis during the study period.	Post-operative period until study completion, an average of 2 years