A Safety and Efficacy Study of Dexamethasone Versus Laser Photocoagulation in Participants With Diabetic Macular Edema

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02121262
• Collaborator: Tigermed Consulting Co., Ltd (Industry)
• Enrollment: 284
• Locations: 18
• Arms: 2
• Actual Duration (Months): 45.8
• Patients Per Site: 15.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of 700 μg dexamethasone versus laser photocoagulation in participants with diabetic macular edema (DME).

Condition or Disease	Intervention/Treatment	Phase
Macular Edema	Drug: Dexamethasone; Procedure: Laser Photocoagulation	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 284 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Dexamethasone Posterior Segment Drug Delivery System Versus Laser Photocoagulation in Patients With Diabetic Macular Edema
• Actual Study Start Date: Jan 8, 2016
• Actual Primary Completion Date: Nov 1, 2019
• Actual Study Completion Date: Nov 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: Laser Photocoagulation Laser photocoagulation was administered in the study eye on Day 1, and on Months 3, 6, and 9, if retreatment indicated.	Procedure: Laser Photocoagulation; Laser photocoagulation on Day 1, and on Months 3, 6, and 9, if retreatment indicated.
Experimental: Dexamethasone Dexamethasone 700 μg was administered as intravitreal injection in the study eye on Day 1, Months 5, and 10.	Drug: Dexamethasone; Dexamethasone 700 μg intravitreal injection in the study eye on Day 1, Months 5, and 10.; Other Names: OZURDEX®

Outcome Measures

Primary Outcome Measures

1. Average Change From Baseline (CFB) in Best Corrected Visual Acuity (BCVA) in the Study Eye [Baseline to Month 12]

   BCVA was measured using an eye chart and is reported as the number of letters read correctly using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. The eligible eye with worse visual acuity was selected as the study eye. The average change was computed by subtracting the baseline BCVA from the area under the BCVA curve (AUC) divided by the total follow-up time for each participant. Analysis of covariance (ANCOVA) model was used for the analysis.

Secondary Outcome Measures

1. Percentage of Participants With BCVA Improvement ≥15 Letters From Baseline in the Study Eye [Baseline to Month 12]

   BCVA was measured using an eye chart and is reported as the number of letters read correctly using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. The eligible eye with worse visual acuity was selected as the study eye.

2. Change From Baseline in CRT by Spectral Domain Optical Coherence Tomography (SD-OCT) in the Study Eye [Baseline to Month 12]

   CRT was assessed using SD-OCT, a non-invasive diagnostic system that provides high-resolution imaging sections of the retina. SD-OCT is performed in the study eye after pupil dilation. A negative change from Baseline indicates improvement and a positive change from baseline indicates worsening. The eligible eye with worse visual acuity was selected as the study eye. ANCOVA model was used for the analysis.

3. Change From Baseline in Total Macular Leakage Area by FA in the Study Eye [Baseline to Month 12]

   FA is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Early and transit images were taken of the study eye. Mid- and late-phase images were taken of the study and non-study eye. Electronic FA images were collected for evaluation by a reading center. The eligible eye with worse visual acuity was selected as the study eye. ANCOVA model was used for the analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of diabetes mellitus (type 1 or type 2)

• Presence of macular edema

Exclusion Criteria:

• Anticipated need for ocular surgery in the study eye during the study

• Laser photocoagulation in the study eye within 3 months

• Cataract surgery within 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University First Hospital	Beijing	Beijing	China	100034
2	People's Hospital of Peking University	Beijing	Beijing	China	100044
3	Beijing Friendship Hospital of Capital Medical University	Beijing	Beijing	China	100050
4	Beijing Hospital	Beijing	Beijing	China	100730
5	Beijing TongRen Hospital	Beijing	Beijing	China	100730
6	Peking Union Medical College Hospital	Beijing	Beijing	China	100730
7	Zhongshan Ophthalmic Center, Sun Yet-Sen University	Guangzhou	Guangdong	China	510060
8	Renmin Hospital of Wuhan University	Wuhan	Hubei	China	430060
9	The Second Xiangya Hospital of Central South University	Changsha	Hunan	China	410011
10	The First Hospital of Nanjing Medical University	Nanjing	Jiangsu	China	210029
11	The 2nd hospital of JiLin University	Changchun	Jilin	China	130041
12	The Eye and ENT Hospital, Affiliated of Fudan University	Shanghai	Shanghai	China	200031
13	West China Hospital, Sichuan University	Chengdu	Sichuan	China	610041
14	Tianjin Eye Hospital	Tianjin	Tianjin	China	300020
15	TianJin Medical University Eye Hospital	Tianjin	Tianjin	China	300384
16	Wenzhou Ophthalmic Centre	Wenzhou	Zhejiang	China	325027
17	Asian Eye Institute	Makati City	Metro Manila	Philippines	1200
18	Peregrine Eye and Laser Institute	Makati City	Metro Manila	Philippines	1209

Sponsors and Collaborators

• Allergan
• Tigermed Consulting Co., Ltd

Investigators

• Study Director: Joanne Li, Allergan

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 13, 2020
• Study Protocol - Apr 25, 2013

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02121262
• Other Study ID Numbers: 206207-026
• First Posted: Apr 23, 2014
• Last Update Posted: Nov 17, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Macular Edema; Edema; Dexamethasone

Study Results

Participant Flow

Arm/Group Title	Laser Photocoagulation	Dexamethasone
Arm/Group Description	Laser photocoagulation was administered in the study eye on Day 1, and on Months 3, 6, and 9, if retreatment indicated.	Dexamethasone 700 μg was administered as intravitreal injection in the study eye on Day 1, Months 5, and 10.
Period Title: Overall Study
STARTED	139	145
Treated	129	145
Modified Intent-to-treat Population	127	145
COMPLETED	108	135
NOT COMPLETED	31	10

Baseline Characteristics

Arm/Group Title	Laser Photocoagulation	Dexamethasone	Total
Arm/Group Description	Laser photocoagulation was administered in the study eye on Day 1, and on Months 3, 6, and 9, if retreatment indicated.	Dexamethasone 700 μg was administered as intravitreal injection in the study eye on Day 1, Months 5, and 10.	Total of all reporting groups
Overall Participants	127	145	272
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.5 (7.73)	59.1 (8.08)	59.3 (7.91)
Sex: Female, Male (Count of Participants)
Female	69 54.3%	64 44.1%	133 48.9%
Male	58 45.7%	81 55.9%	139 51.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	127 100%	145 100%	272 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Chinese	113 89%	129 89%	242 89%
Other	14 11%	16 11%	30 11%
BCVA in the Study Eye (letters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [letters]	55.1 (10.32)	55.7 (11.44)	55.4 (10.91)
Central Retinal Thickness (CRT) by Optical Coherence Tomography (OCT) in the Study Eye (microns) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [microns]	482.1 (154.39)	491.2 (160.80)	486.9 (157.61)
Total Macular Leakage Area by Fluorescein Angiography (FA) in the Study Eye (mm^2) [Mean (Full Range) ]
Mean (Full Range) [mm^2]	30.076	29.644	29.8

Outcome Measures

1. Secondary Outcome

Title	Percentage of Participants With BCVA Improvement ≥15 Letters From Baseline in the Study Eye
Description	BCVA was measured using an eye chart and is reported as the number of letters read correctly using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. The eligible eye with worse visual acuity was selected as the study eye.
Time Frame	Baseline to Month 12

Outcome Measure Data

Analysis Population Description

mITT population included all randomized and treated participants with at least one postbaseline BCVA measurement.

Arm/Group Title	Laser Photocoagulation	Dexamethasone
Arm/Group Description	Laser photocoagulation was administered in the study eye on Day 1, and on Months 3, 6, and 9, if retreatment indicated.	Dexamethasone 700 μg was administered as intravitreal injection in the study eye on Day 1, Months 5, and 10.
Measure Participants	127	145
Number [percentage of participants]	10.2 8%	11.7 8.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Laser Photocoagulation, Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7431
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Based on the Cochran-Mantel-Haenszel (CMH) general association test stratified by baseline BCVA categories.
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; -5.9 to 8.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Average Change From Baseline (CFB) in Best Corrected Visual Acuity (BCVA) in the Study Eye
Description	BCVA was measured using an eye chart and is reported as the number of letters read correctly using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. The eligible eye with worse visual acuity was selected as the study eye. The average change was computed by subtracting the baseline BCVA from the area under the BCVA curve (AUC) divided by the total follow-up time for each participant. Analysis of covariance (ANCOVA) model was used for the analysis.
Time Frame	Baseline to Month 12

Outcome Measure Data

Analysis Population Description

mITT population included all randomized and treated participants with at least one postbaseline BCVA measurement.

Arm/Group Title	Laser Photocoagulation	Dexamethasone
Arm/Group Description	Laser photocoagulation was administered in the study eye on Day 1, and on Months 3, 6, and 9, if retreatment indicated.	Dexamethasone 700 μg was administered as intravitreal injection in the study eye on Day 1, Months 5, and 10.
Measure Participants	127	145
Least Squares Mean (Standard Error) [letters]	1.4 (0.65)	4.3 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Laser Photocoagulation, Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model included the treatment group as the main effect and baseline BCVA score as the covariate.
Method of Estimation	Estimation Parameter	Least Squares Mean (LSM) Difference
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; 1.17 to 4.66
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.89
	Estimation Comments	Null hypothesis-there was no difference in treatment groups of average BCVA CFB in 12-months. Hypothesis test-based on 2-sided test at 0.05 significance level,confidence interval(CI) was constructed between treatment groups in LSM using ANCOVA model.

3. Secondary Outcome

Title	Change From Baseline in CRT by Spectral Domain Optical Coherence Tomography (SD-OCT) in the Study Eye
Description	CRT was assessed using SD-OCT, a non-invasive diagnostic system that provides high-resolution imaging sections of the retina. SD-OCT is performed in the study eye after pupil dilation. A negative change from Baseline indicates improvement and a positive change from baseline indicates worsening. The eligible eye with worse visual acuity was selected as the study eye. ANCOVA model was used for the analysis.
Time Frame	Baseline to Month 12

Outcome Measure Data

Analysis Population Description

mITT population included all randomized and treated participants with at least one postbaseline BCVA measurement. Last observation carried forward (LOCF) was used

Arm/Group Title	Laser Photocoagulation	Dexamethasone
Arm/Group Description	Laser photocoagulation was administered in the study eye on Day 1, and on Months 3, 6, and 9, if retreatment indicated.	Dexamethasone 700 μg was administered as intravitreal injection in the study eye on Day 1, Months 5, and 10.
Measure Participants	127	145
Least Squares Mean (Standard Error) [microns]	-120.3 (13.20)	-209.5 (12.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Laser Photocoagulation, Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Based on ANCOVA model with treatment and baseline BCVA categories as main effects and baseline retinal thickness as the covariate.
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-89.3
	Confidence Interval	(2-Sided) 95%; -122.53 to -56.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 16.89
	Estimation Comments	Null hypothesis was there was no difference in treatment groups in average BCVA CFB in 12-months. Hypothesis test was based on 2-sided test at 0.05 significance level. 2-sided 95% CI was constructed between treatment groups in LSM using ANCOVA model.

4. Secondary Outcome

Title	Change From Baseline in Total Macular Leakage Area by FA in the Study Eye
Description	FA is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Early and transit images were taken of the study eye. Mid- and late-phase images were taken of the study and non-study eye. Electronic FA images were collected for evaluation by a reading center. The eligible eye with worse visual acuity was selected as the study eye. ANCOVA model was used for the analysis.
Time Frame	Baseline to Month 12

Outcome Measure Data

Analysis Population Description

mITT population included all randomized and treated participants with at least one postbaseline BCVA measurement. LOCF was used. Overall number of participants analyzed is the number of participants with data available for analyses.

Arm/Group Title	Laser Photocoagulation	Dexamethasone
Arm/Group Description	Laser photocoagulation was administered in the study eye on Day 1, and on Months 3, 6, and 9, if retreatment indicated.	Dexamethasone 700 μg was administered as intravitreal injection in the study eye on Day 1, Months 5, and 10.
Measure Participants	125	145
Least Squares Mean (Standard Error) [mm^2]	-0.637 (0.8133)	-8.367 (0.7482)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Laser Photocoagulation, Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Based on ANCOVA model with treatment and baseline BCVA categories as main effects and baseline total leakage area as the covariate.
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-7.729
	Confidence Interval	(2-Sided) 95%; -9.7855 to -5.6733
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0443
	Estimation Comments	Null hypothesis was there was no difference in treatment groups in average BCVA CFB in 12-months. Hypothesis test was based on 2-sided test at 0.05 significance level. 2-sided 95% CI was constructed between treatment groups in LSM using ANCOVA model.

Adverse Events

Time Frame	From the first dose up to last dose (Up to Month 12)
Adverse Event Reporting Description	Safety Population included all participants who received the study medication or had the study procedure performed on the study eye.
Arm/Group Title	Laser Photocoagulation		Dexamethasone
Arm/Group Description	Laser photocoagulation was administered in the study eye on Day 1, and on Months 3, 6, and 9, if retreatment indicated.		Dexamethasone 700 μg was administered as intravitreal injection in the study eye on Day 1, Months 5, and 10.
All Cause Mortality
	Laser Photocoagulation		Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/129 (0.8%)		2/145 (1.4%)
Serious Adverse Events
	Laser Photocoagulation		Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/129 (16.3%)		35/145 (24.1%)
Blood and lymphatic system disorders
Anaemia	1/129 (0.8%)		0/145 (0%)
Cardiac disorders
Arteriosclerosis coronary artery	0/129 (0%)		4/145 (2.8%)
Coronary artery disease	4/129 (3.1%)		2/145 (1.4%)
Myocardial infarction	0/129 (0%)		2/145 (1.4%)
Angina unstable	0/129 (0%)		1/145 (0.7%)
Angina pectoris	2/129 (1.6%)		0/145 (0%)
Eye disorders
Cataract	2/129 (1.6%)		8/145 (5.5%)
Vitreous haemorrhage	1/129 (0.8%)		1/145 (0.7%)
Diabetic retinopathy	0/129 (0%)		1/145 (0.7%)
Glaucoma	0/129 (0%)		1/145 (0.7%)
Visual impairment	0/129 (0%)		1/145 (0.7%)
Macular hole	1/129 (0.8%)		0/145 (0%)
Gastrointestinal disorders
Pancreatitis acute	0/129 (0%)		1/145 (0.7%)
Ascites	1/129 (0.8%)		0/145 (0%)
Gastritis	1/129 (0.8%)		0/145 (0%)
Haemorrhoids	1/129 (0.8%)		0/145 (0%)
Hepatobiliary disorders
Cholecystitis	0/129 (0%)		1/145 (0.7%)
Cholecystitis acute	1/129 (0.8%)		0/145 (0%)
Cholecystitis chronic	1/129 (0.8%)		0/145 (0%)
Hepatic cirrhosis	1/129 (0.8%)		0/145 (0%)
Infections and infestations
Bronchitis	0/129 (0%)		1/145 (0.7%)
Pneumonia	0/129 (0%)		1/145 (0.7%)
Upper respiratory tract infection	1/129 (0.8%)		0/145 (0%)
Injury, poisoning and procedural complications
Limb injury	0/129 (0%)		2/145 (1.4%)
Lower limb fracture	0/129 (0%)		2/145 (1.4%)
Fall	0/129 (0%)		1/145 (0.7%)
Foreign body in eye	0/129 (0%)		1/145 (0.7%)
Joint injury	0/129 (0%)		1/145 (0.7%)
Rib fracture	0/129 (0%)		1/145 (0.7%)
Road traffic accident	0/129 (0%)		1/145 (0.7%)
Tibia fracture	1/129 (0.8%)		0/145 (0%)
Investigations
Intraocular pressure increased	0/129 (0%)		1/145 (0.7%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus	3/129 (2.3%)		2/145 (1.4%)
Diabetes mellitus	1/129 (0.8%)		1/145 (0.7%)
Diabetic complication	1/129 (0.8%)		0/145 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/129 (0%)		1/145 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer	1/129 (0.8%)		0/145 (0%)
Nervous system disorders
Cerebral infarction	1/129 (0.8%)		1/145 (0.7%)
Diabetic neuropathy	0/129 (0%)		1/145 (0.7%)
Dizziness	1/129 (0.8%)		0/145 (0%)
Subarachnoid haemorrhage	1/129 (0.8%)		0/145 (0%)
Renal and urinary disorders
Diabetic nephropathy	2/129 (1.6%)		2/145 (1.4%)
Acute kidney injury	1/129 (0.8%)		0/145 (0%)
Chronic kidney disease	1/129 (0.8%)		0/145 (0%)
Skin and subcutaneous tissue disorders
Diabetic foot	1/129 (0.8%)		0/145 (0%)
Vascular disorders
Hypertension	3/129 (2.3%)		2/145 (1.4%)
Other (Not Including Serious) Adverse Events
	Laser Photocoagulation		Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/129 (39.5%)		99/145 (68.3%)
Eye disorders
Cataract	8/129 (6.2%)		16/145 (11%)
Visual impairment	18/129 (14%)		15/145 (10.3%)
Ocular hypertension	1/129 (0.8%)		10/145 (6.9%)
Dry eye	7/129 (5.4%)		8/145 (5.5%)
Vitreous haemorrhage	8/129 (6.2%)		7/145 (4.8%)
Infections and infestations
Upper respiratory tract infection	8/129 (6.2%)		13/145 (9%)
Conjunctivitis	2/129 (1.6%)		13/145 (9%)
Nasopharyngitis	4/129 (3.1%)		8/145 (5.5%)
Urinary tract infection	8/129 (6.2%)		4/145 (2.8%)
Investigations
Intraocular pressure increased	9/129 (7%)		50/145 (34.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A 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 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.