Efficacy of Zylet vs. Lotemax for the Treatment of Ocular Surface Inflammation/MGD/Blepharitis (ZvL)

Tracking Information
First Submitted Date ICMJE	August 2, 2011
First Posted Date ICMJE	October 21, 2011
Results First Submitted Date	April 6, 2017
Results First Posted Date	June 19, 2017
Last Update Posted Date	August 1, 2017
Actual Study Start Date ICMJE	August 2011
Actual Primary Completion Date	March 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 19, 2017)	Ocular Surface Disease Index [ Time Frame: Week 4 Time Point ]OSDI is a 12-question survey used to measure the symptoms of dry eye disease. Each of the 12 individual questions rate one symptom on a 0-4 scale, with 4 meaning that the symptom is present all of the time and 0 meaning the symptom is present none of the time. The overall ODSI score is calculated by adding all of the values from the 12 questions, multiplying that value by 25, and dividing the resulting value by the number of questions answered. This results in an overall scale that ranges from 0-100, with 100 being severe dry eye symptoms and 0 being no dry eye symptoms.; Symptom Assessment iN Dry Eye (SANDE) Frequency Score [ Time Frame: Week 4 Time Point ]Questionnaire given to patients to assess the frequency of dry eye symptoms. The questionnaire utilizes a 100 mm horizontal Visual Analogue Scale technique to quantify the frequency of the patient's dry eye symptoms. Change is quantified from baseline to week 4. The range of the SANDE frequency scale is 0-100, with 0 being the minimum level of frequency of dry eye symptoms and 100 being the maximum level of frequency of dry eye symptoms.; Symptom Assessment iN Dry Eye (SANDE) Severity Score [ Time Frame: Week 4 Time Point ]Questionnaire given to patients to assess the severity of dry eye symptoms. The questionnaire utilizes a 100 mm horizontal Visual Analogue Scale technique to quantify the severity of the patient's dry eye symptoms. Change is quantified from baseline to week 4. The range of the SANDE severity scale is 0-100, with minimum level of severity of dry eye symptoms and 100 being the maximum level of severity of dry eye symptoms.; Corneal Fluorescein Staining Score [ Time Frame: Week 4 Time Point ]Corneal Fluorescein Staining is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The CFS scale ranges from 0 to 15 scale, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of corneal epitheliopathy.
Original Primary Outcome Measures ICMJE; (submitted: October 19, 2011)	Efficacy of Treatment [ Time Frame: 4 and 8 weeks after taking the first dose ]; Efficacy will be evaluated comparing a change from baseline in symptom questionnaires, presence of inflammatory cells, and lid and gland evaluation scores.
Change History	Complete list of historical versions of study NCT01456780 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy of Zylet vs. Lotemax for the Treatment of Ocular Surface Inflammation/MGD/Blepharitis
Official Title ICMJE	Relative Efficacy of Loteprednol (Lotemax®) vs. Loteprednol/Tobramycin (Zylet®) in Treatment of Chronic Ocular Surface Inflammation Associated With Meibomian Gland Dysfunction (MGD)/Posterior Blepharitis
Brief Summary	This is a Phase IV, single site, randomized, double masked, parallel control clinical trial of 60 subjects to investigate the variance of efficacy between Lotemax® and Zylet® for treatment of ocular surface inflammation due to meibomian gland dysfunction (MGD). Efficacy will be measured by in-vivo confocal microscopy, corneal fluorescein staining, grading of meibomian gland dysfunction and validated ocular symptom assessment questionnaire.
Detailed Description	Posterior blepharitis is a common chronic eyelid condition that is described as generalized inflammation of the posterior lid margin and associated with inflammation of the ocular surface and with symptoms of burning, irritation, and discomfort. Posterior blepharitis is associated with various disorders of the meibomian glands, known collectively as meibomian gland dysfunction (MGD). It is associated either with obstruction and inflammation of the meibomian glands or, less commonly, atrophy of the meibomian glands. Clinically, MGD often presents with inspissated meibomian glands, oily tear film, as well as inflammation and vascularization of the meibomian gland orifices. Papillary hypertrophy of the tarsal conjunctiva and corneal punctate epitheliopathy are often present, and there are prominent associations with dermatoses, such as acne rosacea, seborrhoeic dermatitis, and atopic dermatitis. Evidence from several sources suggests that MGD of sufficient extent and degree is associated with a deficient tear lipid layer, an increase in tear evaporation, and the occurrence of an evaporative dry eye. In fact MGD is considered to be the most common cause of evaporative dry eye. Individuals with MGD often complain of significant discomfort, including burning, itching, irritation, and photophobia. They may also have other associated symptoms of dry eye and may be plagued by blurred vision, gradual contact lens intolerance. Furthermore, these patients may become functionally handicapped by the negative impact of dry eye on their crucial daily activities such as working, reading, using computer, and driving. Despite the high incidence of posterior blepharitis, there is currently no consistently effective treatment for this condition and it still remains a therapeutic challenge. Posterior blepharitis has traditionally been managed with eyelid hygiene, topical antibiotics (erythromycin or bacitracin ointments), oral tetracyclines (tetracycline, doxycycline, or minocycline) and corticosteroids which are often time consuming, frustrating, and frequently ineffective or variably effective. The purpose of this study is to compare the effectiveness of topical loteprednol (corticosteroid) vs. the combination of loteprednol and tobramycin (corticosteroid and antibiotic) against an artificial tear. It is critical to determine to what extent the addition of an antibiotic to a topical steroid can enhance the therapeutic efficacy of the treatment.
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Meibomian Gland Dysfunction; Posterior Blepharitis
Intervention ICMJE	Drug: Loteprednol/tobramycin Zylet (loteprednol/tobramycin) drops, 1 drop twice a day for 4 weeks. Other Name: Zylet; Drug: Loteprednol Eye drops, 1 drop twice a day for 4 weeks Other Name: Lotemax; Drug: B+L Advanced Eye Relief Lubricant Drop Bausch + Lomb (B+L) Advanced Eye Relief Lubricant Drop (Artificial Tears), 1 drop twice a day for 4 weeks. Other Name: artificial tears
Study Arms	Active Comparator: Zylet Subject randomized to this arm will be treated with Zylet (Loteprednol/tobramycin), twice a day, for 4 weeks. Zylet is a combination of loteprednol and tobramycin. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Tobramycin is an antibiotic. Intervention: Drug: Loteprednol/tobramycin; Active Comparator: Lotemax Subject randomized to this arm will be treated with Lotemax, twice a day, for 4 weeks. Lotemax is also known as loteprednol. Loteprednol is in a class of drugs called corticosteroids. Loteprednol inhibits processes in the body that cause inflammation. Intervention: Drug: Loteprednol; Placebo Comparator: B+L Advanced Eye Relief Lubricant Drop Subject randomized to this arm will be treated with B+L Advanced Eye Relief Lubricant Eye Drops (Artificial Tears), twice a day, for 4 weeks. Intervention: Drug: B+L Advanced Eye Relief Lubricant Drop
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: October 19, 2011)	60
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	June 2017
Actual Primary Completion Date	March 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Male or female; At least 18 years of age; Has not worn contact lenses, except for bandage contact lens or rigid gas permeable lens, for at least 2 weeks prior to the study and agrees to not wear contact lenses during study; Patient is in generally good & stable overall health; Minimum corneal fluorescein staining of 4 in at least one eye; OSDI score >22; The patient must have a diagnosis of posterior blepharitis; A negative urine pregnancy test result for women of childbearing potential; Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.; Normal lid position and closure; Ability to understand and provide informed consent to participate in this study; Willingness to follow study instructions and likely to complete all required visits Exclusion Criteria: History of Stevens-Johnson syndrome or ocular pemphigoid; History of eyelid surgery; Intra-ocular surgery or ocular laser surgery within 3 months; History of microbial keratitis, including herpes; Active ocular allergies; Corneal epithelial defect > 1mm2; Any change in use of topical anti-inflammatories, such as steroids, Restasis, or NSAID within the past 2 weeks; Any change in dosage of tetracycline compounds (tetracycline, doxycycline, and minocycline) within the past two weeks; Use of isotretinoin (Accutane) within the past 6 months; Pregnant or lactating women; Signs of current infection, including fever and current treatment with antibiotics; Active liver, renal, or hematologic disease; The use of any other investigational drug; Individuals with a known history of glaucoma, individuals with IOP >22 Hg in either eye and individuals with a known family history of glaucoma in primary (first degree) relatives (ie. mother, father, sibling or child)
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01456780
Other Study ID Numbers ICMJE	11-048H
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement	Plan to Share IPD: Yes
Responsible Party	Reza Dana, MD, Massachusetts Eye and Ear Infirmary
Study Sponsor ICMJE	Massachusetts Eye and Ear Infirmary
Collaborators ICMJE	Bausch & Lomb Incorporated
Investigators ICMJE	Principal Investigator: Reza Dana, MD, MPH, MSc Massachusetts Eye and Ear Infirmary
PRS Account	Massachusetts Eye and Ear Infirmary
Verification Date	July 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP