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Clinical Effects and Safety of 3% Diquafosol After Cataract Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02608489
Recruitment Status : Completed
First Posted : November 18, 2015
Results First Posted : October 17, 2016
Last Update Posted : October 17, 2016
Sponsor:
Information provided by (Responsible Party):
Jin Kwon Chung, Soonchunhyang University Hospital

Tracking Information
First Submitted Date  ICMJE November 14, 2015
First Posted Date  ICMJE November 18, 2015
Results First Submitted Date  ICMJE April 14, 2016
Results First Posted Date  ICMJE October 17, 2016
Last Update Posted Date October 17, 2016
Study Start Date  ICMJE January 2014
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 22, 2016)
  • an Ocular Surface Disease Index (OSDI) Questionnaire That is Related to Dry Eye Severity. [ Time Frame: 12 weeks ]
    The OSDI questionnaire consists of 12 questions that evaluate subjective symptoms related to dry eye and vision The score ranges were between 0 and 100 scores and the higher scores represent a worse outcome.
  • Schirmer I Test Without Anesthesia That is Related to Dry Eye Severity. [ Time Frame: 12 weeks ]
    Schirmer paper strips were placed into the temporal one third of the lower conjunctival sac for 5 min and the wetness on the strips was measured.
  • Changes in HOAs After Blinking That is Related to Dry Eye Severity. [ Time Frame: 12 weeks ]
    Corneal HOAs and serial measurement of ocular total HOAs were evaluated using a KR-1W wavefront analyzer (Topcon Medical System, Inc., Tokyo, Japan). Serial measurement of total ocular HOAs was measured every second for 10 s after complete blinking in continuous measurement mode. The difference between the fifth and first HOA was used to evaluate the tear film instability.
  • Tear Break-up Time (TBUT) That is Related to Dry Eye Severity. [ Time Frame: 12 weeks ]
    TBUT was assessed by instillation of a drop of 2% sterile fluorescein into the conjunctival sac and recording the interval between the last complete blink and the first appearance of a dry spot or disruption of the tear film.
  • Corneal Fluorescein Staining That is Related to Dry Eye Severity. [ Time Frame: 12 weeks ]
    Ocular surface damage was assessed by the National Eye Institute (NEI) workshop grading system, and corneal fluorescein staining was evaluated. Instillation of fluorescein in both eyes. After 1 or 2 full blinks, the intensity of staining of both cornea was scored. According to the National Eye Institute (NEI) workshop grading system, the cornea was divided into five sections. The minimum staining score was 0 and the maximum staining score was 15 points (up to 3 points for each section). 0 : best score (no corneal damage) 15 : worst score (severe corneal damages)
  • Lissamine Green (LG) Conjunctival Staining That is Related to Dry Eye Severity [ Time Frame: 12 weeks ]
    Ocular surface damage was assessed by the National Eye Institute (NEI) workshop grading system, and conjunctival LG staining were evaluated. Instillation of 1% lissamine green in both eyes. After 1 or 2 full blinks, the intensity of staining of both medial and lateral bulbar conjunctiva was cored. According to the National Eye Institute (NEI) workshop grading system, the conjunctiva was divided into six sections. The minimum staining score was 0 and the maximum staining score was 18 points (up to 3 points for each section). 0 : best score (no conjunctival damage) 18 : worst score (severe conjunctival damages)
Original Primary Outcome Measures  ICMJE
 (submitted: November 17, 2015)
  • an Ocular Surface Disease Index (OSDI) Questionnaire That is Related to Dry Eye Severity. [ Time Frame: 1 year ]
    The OSDI questionnaire consists of 12 questions that evaluate subjective symptoms related to dry eye and vision
  • Schirmer I Test Without Anesthesia That is Related to Dry Eye Severity. [ Time Frame: 1 year ]
    Schirmer paper strips were placed into the temporal one third of the lower conjunctival sac for 5 min and the wetness on the strips was measured.
  • Changes in HOAs After Blinking That is Related to Dry Eye Severity. [ Time Frame: 1 year ]
    Corneal HOAs and serial measurement of ocular total HOAs were evaluated using a KR-1W wavefront analyzer (Topcon Medical System, Inc., Tokyo, Japan). Serial measurement of total ocular HOAs was measured every second for 10 s after complete blinking in continuous measurement mode. The difference between the fifth and first HOA was used to evaluate the tear film instability.
  • Tear Break-up Time (TBUT) That is Related to Dry Eye Severity. [ Time Frame: 1 year ]
    TBUT was assessed by instillation of a drop of 2% sterile fluorescein into the conjunctival sac and recording the interval between the last complete blink and the first appearance of a dry spot or disruption of the tear film.
  • corneal fluorescein staining, and lissamine green (LG) conjunctival staining that are related to dry eye severity. [ Time Frame: 1 year ]
    Ocular surface damage was assessed by the National Eye Institute (NEI) workshop grading system, and corneal fluorescein staining and conjunctival LG staining were evaluated. The maximum staining score is 15 for the cornea and 18 for the conjunctiva.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2016)
  • Grades of Anterior Chamber Cells. [ Time Frame: 12 weeks ]
    Anterior chamber inflammation was examined with a slit-lamp clinically, and divided into six grades using the Standardization of Uveitis Nomenclature (SUN) working group grading scheme. grade 0 : <1 cell in field, grade 0.5 : 1-5 cells in field, grade 1 : 6-15 cells in field, grade 2 : 16-25 cells in field grade 3 : 26-50 cells in field, grade 4 : >50 cells in field Field size is a 1 mm X 1 mm slit beam
  • Number of Participants Who Stop Using the Eye Drops Due to Drug-related Discomfort [ Time Frame: 12 weeks ]
    Drug-related discomfort is defined as having started after eye drop instillation and lasting several minutes, occurring every time during instillation at any time up to 12 weeks into the follow-up period. Patients that had any adverse events or wanted to stop using the eye drops were excluded from the study, but these patients were included in the safety evaluation.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2015)
  • number of participants with anterior chamber inflammation. [ Time Frame: 1 year ]
    Anterior chamber inflammation was examined with a slit-lamp clinically, and divided into six grades using the Standardization of Uveitis Nomenclature (SUN) working group grading scheme.
  • Number of Participants Who Stop Using the Eye Drops Due to Drug-related Discomfort [ Time Frame: 1 year ]
    Drug-related discomfort is defined as having started after eye drop instillation and lasting several minutes, occurring every time during instillation at any time up to 12 weeks into the follow-up period.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Effects and Safety of 3% Diquafosol After Cataract Surgery
Official Title  ICMJE Clinical Effects and Safety of 3% Diquafosol Ophthalmic Solution for Patients With Dry Eye After Cataract Surgery: A Randomized Controlled Trial
Brief Summary The purpose of this study is determine whether 3% diquafosol and 0.1% sodium hyaluronate are effective and safe in the treatment of patients with dry eye after cataract surgery.
Detailed Description

Study group and protocol: This was a prospective open-label randomized study. All patients were given a full explanation of the study, and written informed consent was obtained from all participants. The study protocol adhered to the tenets of the Declaration of Helsinki. The Institutional Review Board and Ethics Committee, Soonchunhyang University Seoul Hospital, approved this study (SCHUH 2013-12-012). Patients were randomly allocated into the diquafosol group (D group) or the hyaluronate group (H group) using a simple unrestricted randomization method by the controller. The D group used 3% diquafosol tetrasodium ophthalmic solution (Diquas®; Santen Pharmaceutical Co., Ltd., Osaka, Japan) six times a day and the H group used 0.1% sodium hyaluronate ophthalmic solution (Hyalein®; Santen Pharmaceutical Co., Ltd., Osaka, Japan) six times a day. Both groups instilled each eye drop from postoperative day 1 to postoperative week 12.

Participants: Consecutive patients aged 20-90 years with bilateral or unilateral cataract undergoing uncomplicated phacoemulsification and intraocular lens (IOL) implantation at Soonchunhyang University Hospital between January 2014 and January 2015 were enrolled. The inclusion criteria were patients with mild to moderate dry eye (level 1 or 2) based on the dry eye severity scale adopted by the Dry Eye Workshop (DEWS) report and who used only artificial tears occasionally1, and patients without or with mild blepharitis.18 The exclusion criteria were presence of any complications after cataract surgery such as cystoid macular edema, patients using any topical eye drops on a regular basis, treatment history of dry eye beyond artificial tears, any ocular surgery within the prior 6 months, contact lens wear, serious ocular surface disease (e.g., Sjögren's syndrome, ocular pemphigoid, conjunctival scarring, chemical injury), lacrimal or eyelid disease (e.g., moderate to severe blepharitis18), use of concomitant medications that could cause dry eye (e.g., antihistamines, antidepressants, decongestants, anticholinergic drugs), and allergy to any of the study medications.

Objective and subjective clinical assessments of dry eye: All patients underwent ophthalmic examinations preoperatively and postoperatively in the order of following : uncorrected distant visual acuity (UDVA) test, an ocular surface disease index (OSDI) questionnaire, Schirmer I test without anesthesia, changes in HOAs after blinking, tear break-up time (TBUT), corneal fluorescein staining, and lissamine green (LG) conjunctival staining. Eyelid and anterior chamber cells were evaluated by slit-lamp biomicroscopy to assess the presence of blepharitis/meibomian gland plugging and intraocular inflammation. Routine postoperative examinations were scheduled for 1 week, 4 weeks, and 12 weeks after surgery.

Efficacy and safety evaluation: To evaluate the efficacy of the two different eye drops, we compared each measurement between the two groups throughout the study period, and at each follow-up, and also compared the patterns of changes in each group to identify which group recovered earlier. we evaluated the safety of the two eye drops, including anterior chamber inflammation and discontinuation of the eye drops due to drug-related discomfort. Patients that had any adverse events or wanted to stop using the eye drops were excluded from the study, but these patients were included in the safety evaluation.

Surgical procedure: A 2.8 mm clear corneal incision was made at the location of the steep corneal astigmatism axis. A standard phacoemulsification technique was used with topical anesthesia with 2% lidocaine. A foldable IOL was implanted into the capsular bag. There was no suture at the corneal incision site. Patients received moxifloxacin (Vigamox; Alcon, Fort Worth, TX), which is a preservative-free formulation, and rimexolone (Vexol; Alcon), which contains 0.01% BAK, four times a day after surgery for 4 weeks.

Statistical analysis: For statistical analysis, UDVA was converted from Snellen into logMAR values. Baseline data were compared between the groups using the Mann-Whitney U-test, Fisher's exact test, and the linear mixed model after adjusting for inter-eye correlations, age, and sex. In addition, another mixed model was used to compare measurement data between the two groups by considering the correlation between both eyes of each patient at each follow-up. To obtain an overall comparison between treatment responses throughout the study period considering the two levels of correlation in subjects and follow-up, a bivariate generalized linear mixed (GLM) model with asymmetric random effects was used. In the last step, a bivariate GLM model was also used to identify the patterns of changes in measured data throughout the study period. The intergroup differences in adverse events were analyzed using Fisher's exact test. SPSS software (version 21, SPSS, Inc., Chicago, IL) was used for all statistical analyses, and P < .05 was taken to indicate statistical significance.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Dry Eye Syndromes
Intervention  ICMJE
  • Drug: Diquafosol (Diquas)
    Diquafosol group used diquafosol 6 times a day during study period.
  • Drug: Sodium Hyaluronate (Hyalein)
    Hyaluronate group used sodium hyaluronate 6 times a day during study period.
Study Arms  ICMJE
  • Active Comparator: Diqufosol
    3% Diquafosol Tetrasodium Ophthalmic Solution
    Intervention: Drug: Diquafosol (Diquas)
  • Placebo Comparator: Hyaluronate
    0.1% Sodium Hyaluronate Ophthalmic Solution
    Intervention: Drug: Sodium Hyaluronate (Hyalein)
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: August 22, 2016)
86
Original Actual Enrollment  ICMJE
 (submitted: November 17, 2015)
150
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Bilateral or unilateral cataract undergoing phacoemulsification and intraocular lens (IOL) implantation at Soonchunhyang University Hospital between January 2014 and January 2015
  • Patients with mild to moderate dry eye (level 1 or 2) based on the dry eye severity scale adopted by the Dry Eye Workshop (DEWS) report and who used only artificial tears occasionally

Exclusion Criteria:

  • Presence of any complications after cataract surgery such as cystoid macular edema
  • Patients using any topical eye drops on a regular basis
  • Treatment history of dry eye beyond artificial tears
  • Any ocular surgery within the prior 6 months
  • Contact lens wear
  • Serious ocular surface disease (e.g., Sjögren's syndrome, ocular pemphigoid, conjunctival scarring, chemical injury)
  • Eyelid or lacrimal disease
  • Use of concomitant medications that could cause dry eye and allergy to any of the study medications
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02608489
Other Study ID Numbers  ICMJE SCHUH 2013-12-012
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jin Kwon Chung, Soonchunhyang University Hospital
Study Sponsor  ICMJE Soonchunhyang University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jin Kwon Chung, MD Soonchunhyang University Hospital
PRS Account Soonchunhyang University Hospital
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP