DWCIE: Daily Wear Corneal Infiltrative Event Study

• Sponsor: University Hospitals Cleveland Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00937105
• Collaborator: Alcon Research (Industry)
• Enrollment: 218
• Location: 1
• Arms: 2
• Duration (Months): 27
• Patients Per Site Per Month: 8.1

Study Details

Study Description

Brief Summary

This DWCIE Study is a prospective cohort study of patients fit to the FDA approved and marketed lotrafilcon A (Ciba Vision, Air Optix Night & Day Aqua) soft contact lenses for daily wear (DW) with monthly disposal. 218 healthy myopic (nearsighted) or hyperopic (farsighted) patients with minimal or no astigmatism and no contraindications to DW lens use will be followed for 1 year. The primary outcome is the risk of development of a corneal inflammatory event (CIE) as defined by slit lamp findings and patient symptoms. The main exposure of interest is microbial contamination of study lenses.

Condition or Disease	Intervention/Treatment	Phase
Myopia; Hyperopia; Corneal Infiltrative Events	Device: lotrafilcon A contact lenses; Device: Renu Multiplus; Device: Clear Care	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 218 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Infiltrative Events During Silicone Hydrogel Daily Contact Lens (Daily Wear Corneal Infiltrative Event (DWCIE) Study)
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ReNu Multiplus and lotrafilcon A lenses ReNu Multiplus contact lens care solution	Device: lotrafilcon A contact lenses; FDA approved soft contact lenses; Other Names: Air Optix Night & Day Aqua contact lenses ; Device: Renu Multiplus
Active Comparator: Clear Care solution and lotrafilcon A lenses Clear Care Contact Lens Care Solution	Device: lotrafilcon A contact lenses; FDA approved soft contact lenses; Other Names: Air Optix Night & Day Aqua contact lenses ; Device: Clear Care

Outcome Measures

Primary Outcome Measures

1. Number of Participants Developing a Corneal Inflammatory Event (CIE) [up to 1 year]

   Raw number of participants in each solution arm developing CIE over 12 month follow-up period

Secondary Outcome Measures

1. Number of Participants With CIE Stratified by Microbial Bioburden on Lenses [up to 1 year]

   Microbial bioburden on lenses was determined with predetermined cutoffs to identify substantial bioburden as high levels of normal flora or presence of pathogenic abnormal flora on lenses

2. Number of Participants With CIE Based Stratified by Presence or Absence of Corneal Staining Induced by Solution Use. [up to 1 year]

   Presumed solution induced corneal staining was defined as diffuse punctate fluorescein staining of at least 15% surface area in at least 4 of 5 zones

3. Number of Participants With CIE Stratified by Microbial Bioburden on Lens Cases [up to 1 year]

   Microbial bioburden within lens storage cases was determined with predetermined cutoffs to identify substantial bioburden as high levels of normal flora or presence of pathogenic abnormal flora

4. Number of Participants With CIE Stratified by Overall Microbial Bioburden on Lid Margins [up to 1 year]

   Microbial bioburden on lid margins was determined with predetermined cutoffs to identify substantial bioburden as high levels of normal flora or presence of pathogenic abnormal flora on lids

5. Number of Participants With CIE Stratified by CNS Microbial Bioburden on Lid Margins [up to 1 year]

   Microbial bioburden with coagulase negative staphylococci (CNS) on lid margins was determined with predetermined cutoffs to identify substantial bioburden as high levels of normal CNS flora on lids

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. The patient must be at least 15 years old.

2. The patient must be free of any anterior segment disorders.

3. The patient must have a spectacle corrected spherical refractive error between +5.50 D and -11.00 D with less than or equal to 1.00 D refractive cylinder.

4. The patient must be correctable to 20/25 or better with spectacles.

5. Flat and steep corneal curvatures from Simulated Keratometry readings must be between 39.00 and 48.00 D.

6. Can be successfully fit with lotrafilcon A lenses at the enrollment visit.

Exclusion Criteria

1. The patient has worn rigid gas permeable lenses within the last 30 days or polymethylmethacrylate lenses within the last 3 months.

2. The patient must not be a current successful daily wear user of lotrafilcon A lenses. They may have tried lotrafilcon A lenses in the past, but must not have successfully worn these lenses for daily wear within the last 12 months.

3. The patient has an autoimmune disease (except for Hashimoto's Thyroiditis), immunocompromising disease, connective tissue disease, atopic dermatitis, insulin dependent diabetes, or any other systemic disease that in the investigator's opinion will affect ocular health.

4. The patient is taking chronic systemic medications such as corticosteroids, antimetabolites, or non-steroidal anti-inflammatory agents or any other medication that in the investigator's opinion will affect ocular physiology or study participation.

5. The patient has any ocular disease or condition such as aphakia, corneal dystrophies, corneal edema, external ocular infection, iritis, or had any anterior segment surgery.

6. The patient is taking any ocular medications. If a patient was previously taking any ocular medications, the medications must have been discontinued at least 2 weeks prior to enrollment.

7. The patient must have less than or equal to grade 2 on any of the slit lamp observations of: upper tarsal papilla, corneal staining, corneal neovascularization, conjunctival injection, and lid erythema or scales. Slit lamp findings higher than grade 2 bias the patient toward an adverse event and it may be difficult to detect true change related to contact lens use.

8. The patient is pregnant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Ophthalmology University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• University Hospitals Cleveland Medical Center
• Alcon Research

Investigators

• Principal Investigator: Loretta Szczotka-Flynn, OD, PhD, University Hospitals Cleveland Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Loretta Szczotka-Flynn, OD, PhD, University Hospitals Cleveland Medical Center
• ClinicalTrials.gov Identifier: NCT00937105
• Other Study ID Numbers: 001
• First Posted: Jul 10, 2009
• Last Update Posted: Mar 10, 2014
• Last Verified: Jan 1, 2014

• Additional relevant MeSH terms: Hyperopia

Study Results

Participant Flow

Recruitment Details	From November 2009 to February 2012, 218 participants were randomized at the University Hospitals Case Medical Center Eye Institute.
Pre-assignment Detail	Existing soft lens wearers or non contact lens wearers were recruited, no wash out period was required

Arm/Group Title	Lotrafilcon A Lenses and Clear Care	Lotrafilcon A Lenses and Renu Multiplus
Arm/Group Description
Period Title: Overall Study
STARTED	109	109
COMPLETED	69	70
NOT COMPLETED	40	39

Baseline Characteristics

Arm/Group Title	Lotrafilcon A and Renu	Lotrafilcon A and Clear Care	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	109	109	218
Age (Count of Participants)
<=18 years	1 0.9%	2 1.8%	3 1.4%
Between 18 and 65 years	108 99.1%	107 98.2%	215 98.6%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.4 (11.3)	34.9 (11.5)	34.7 (11.4)
Sex: Female, Male (Count of Participants)
Female	78 71.6%	75 68.8%	153 70.2%
Male	31 28.4%	34 31.2%	65 29.8%
Region of Enrollment (participants) [Number]
United States	109 100%	109 100%	218 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Developing a Corneal Inflammatory Event (CIE)
Description	Raw number of participants in each solution arm developing CIE over 12 month follow-up period
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

This primary analysis includes the cohort of all 218 randomized participants. The measured values stratify participants by solution group, however, the statistical analysis reports on the entire cohort (both solution groups) consistent with the primary aim of the study.

Arm/Group Title	Lotrafilcon A Lenses and Renu	Lotrafilcon A Lenses and Clear Care
Arm/Group Description
Measure Participants	109	109
Number [participants]	6 5.5%	7 6.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lotrafilcon A Lenses and Renu, Lotrafilcon A Lenses and Clear Care
	Comments	Cumulative Unadjusted Probability of Remaining Infiltrate Free in entire Cohort
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cumulative Probability of no-CIE
	Estimated Value	92.8
	Confidence Interval	(2-Sided) 95%; 88.6 to 96.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With CIE Stratified by Microbial Bioburden on Lenses
Description	Microbial bioburden on lenses was determined with predetermined cutoffs to identify substantial bioburden as high levels of normal flora or presence of pathogenic abnormal flora on lenses
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

All participants in which valid lens bioburden data was available

Arm/Group Title	Participants With Microbial Bioburden on Lenses	Participants Without Microbial Bioburden on Lenses
Arm/Group Description
Measure Participants	53	139
Number [participants]	4 3.7%	6 5.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lotrafilcon A Lenses and Renu, Lotrafilcon A Lenses and Clear Care
	Comments	To determine if microbial contamination of lenses is a risk factor for CIE
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3923
	Comments
	Method	Regression, Cox
	Comments	Univariate hazard ratio provided because non-significant finding did not enter into multivariate analyses
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.737
	Confidence Interval	(2-Sided) 95%; 0.49 to 6.156
	Parameter Dispersion	Type: Value:
	Estimation Comments	referent is no substantial lens bioburden

3. Secondary Outcome

Title	Number of Participants With CIE Based Stratified by Presence or Absence of Corneal Staining Induced by Solution Use.
Description	Presumed solution induced corneal staining was defined as diffuse punctate fluorescein staining of at least 15% surface area in at least 4 of 5 zones
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

Number of participants with valid presumed solution induced corneal staining data in each group

Arm/Group Title	Participants With Corneal Staining	Participants Without Corneal Staining
Arm/Group Description
Measure Participants	49	145
Number [participants]	2 1.8%	8 7.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lotrafilcon A Lenses and Renu, Lotrafilcon A Lenses and Clear Care
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7943
	Comments
	Method	Regression, Cox
	Comments	Univariate hazard ratio provided because non-significant finding did not enter into multivariate analyses
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.316
	Confidence Interval	(2-Sided) 95%; 0.167 to 10.393
	Parameter Dispersion	Type: Value:
	Estimation Comments	referent is no corneal staining

4. Secondary Outcome

Title	Number of Participants With CIE Stratified by Microbial Bioburden on Lens Cases
Description	Microbial bioburden within lens storage cases was determined with predetermined cutoffs to identify substantial bioburden as high levels of normal flora or presence of pathogenic abnormal flora
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

All participants in which valid lens case bioburden data was available

Arm/Group Title	Participants With Microbial Bioburden on Lens Cases	Participants With no Microbial Bioburden on Lens Cases
Arm/Group Description
Measure Participants	119	51
Number [participants]	5 4.6%	3 2.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lotrafilcon A Lenses and Renu, Lotrafilcon A Lenses and Clear Care
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5894
	Comments
	Method	Regression, Cox
	Comments	Univariate hazard ratio provided because non-significant finding did not enter into multivariate analyses
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.674
	Confidence Interval	(2-Sided) 95%; 0.161 to 2.822
	Parameter Dispersion	Type: Value:
	Estimation Comments	referent is no substantial case bioburden

5. Secondary Outcome

Title	Number of Participants With CIE Stratified by Overall Microbial Bioburden on Lid Margins
Description	Microbial bioburden on lid margins was determined with predetermined cutoffs to identify substantial bioburden as high levels of normal flora or presence of pathogenic abnormal flora on lids
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

All participants in which valid lens bioburden data was available

Arm/Group Title	Participants With Microbial Bioburden on Lid Margins	Participants With no Microbial Bioburden on Lid Margins
Arm/Group Description
Measure Participants	154	40
Number [participants]	10 9.2%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lotrafilcon A Lenses and Renu, Lotrafilcon A Lenses and Clear Care
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1742
	Comments	Univariate hazard ratio provided because non-significant finding did not enter into multivariate analyses
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.406
	Confidence Interval	(2-Sided) 95%; 0.678 to 8.537
	Parameter Dispersion	Type: Value:
	Estimation Comments	referent is no substantial overall lid bioburden

6. Secondary Outcome

Title	Number of Participants With CIE Stratified by CNS Microbial Bioburden on Lid Margins
Description	Microbial bioburden with coagulase negative staphylococci (CNS) on lid margins was determined with predetermined cutoffs to identify substantial bioburden as high levels of normal CNS flora on lids
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

All participants in which valid lids bioburden data was available

Arm/Group Title	Participants With CNS Bioburden on Lid Margins	Participants With no CNS Bioburden on Lid Margins
Arm/Group Description
Measure Participants	84	110
Number [participants]	8 7.3%	2 1.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lotrafilcon A Lenses and Renu, Lotrafilcon A Lenses and Clear Care
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Regression, Cox
	Comments	Multivariate model adjusted for solution, gender and age
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	5.22
	Confidence Interval	(2-Sided) 95%; 1.10 to 24.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	referent is no substantial CNS lid bioburden

Adverse Events

Time Frame	up to 1 year
Adverse Event Reporting Description	CIE definitions adopted from the standards as listed in the "Institute for Eye Research/L.V. Prasad Eye Institute (IER/LVPEI) Guide To Corneal Infiltrative Conditions Contact Lens Papillary Conjunctivitis was a clinical diagnosis that required temporary or permanent discontinuation of lens wear due to large papilla upon upper lid eversion
Arm/Group Title	Entire Cohort of Lotrafilcon A Users
Arm/Group Description
All Cause Mortality
	Entire Cohort of Lotrafilcon A Users
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Entire Cohort of Lotrafilcon A Users
	Affected / at Risk (%)	# Events
Total	1/218 (0.5%)
Eye disorders
microbial keratitis	1/218 (0.5%)
Other (Not Including Serious) Adverse Events
	Entire Cohort of Lotrafilcon A Users
	Affected / at Risk (%)	# Events
Total	23/218 (10.6%)
Eye disorders
corneal infiltrative event	12/218 (5.5%)
Contact Lens Papillary Conjunctivitis	11/218 (5%)

Limitations/Caveats

Mostly asymptomatic CIE events occurred which limited the ability to retrieve the lens worn (for culture) precisely at the time of CIE development; this may have hindered our ability to capture bioburden at the time of the adverse event.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.