Safety and Efficacy of a New Treatment in Combination With Laser for Diabetic Macular Edema

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00464685
• Collaborator: (none)
• Enrollment: 253
• Locations: 2
• Arms: 2
• Actual Duration (Months): 33.3
• Patients Per Site: 126.5
• Patients Per Site Per Month: 3.8

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of the intravitreal implant of dexamethasone with laser treatment vs. laser treatment alone in patients with diabetic macular edema.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema	Drug: Dexamethasone; Drug: Sham injection; Procedure: Laser Photocoagulation	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 253 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Actual Study Start Date: May 1, 2007
• Actual Primary Completion Date: Feb 8, 2010
• Actual Study Completion Date: Feb 8, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 700 µg Dexamethasone Implant and Laser Photocoagulation Initial intravitreal injection of 700 µg dexamethasone with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.	Drug: Dexamethasone; Initial intravitreal injection of 700 µg dexamethasone with up to 1 additional treatment based on re-treatment criteria.; Other Names: Posurdex® ; Procedure: Laser Photocoagulation; Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.
Sham Comparator: Sham Implant and Laser Photocoagulation Initial sham injection with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.	Drug: Sham injection; Initial sham injection with up to 1 additional treatment based on re-treatment criteria.; Procedure: Laser Photocoagulation; Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With at Least 10 Letters of Improvement in Best Corrected Visual Acuity (BCVA) From Baseline in the Study Eye [Baseline, Month 12]

   BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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 indicates improvement and a decrease in the number of letters read correctly indicates a worsening.

Secondary Outcome Measures

1. Change From Baseline in BCVA in the Study Eye [Baseline, Month 12]

   BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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 indicates improvement and a decrease in the number of letters read correctly indicates a worsening.

2. Change From Baseline in Central Subfield Retinal Thickness in the Study Eye [Baseline, Month 12]

   Central subfield retinal thickness is assessed in the study eye by Optical Coherence Tomography (OCT). The central subfield is an area in the retina (back of the eye). OCT is a laser-based, noninvasive, diagnostic system that provides high-resolution, three-dimensional images of the retina from which retinal thickness can be measured. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening.

3. Change From Baseline in the Focal Leakage Area in the Study Eye [Baseline, Month 12]

   Focal leakage area in the study eye is assessed using fluorescein angiography. A positive number change from baseline indicates a worsening and a negative number change from baseline indicates an improvement.

4. Time to Retreatment in the Study Eye [12 Months]

   Time to retreatment in the study eye is defined as the number of days between the initial treatment and re-treatment with the study medication.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 18 years of age or older with diabetic macular edema

• Decrease in visual acuity in at least one eye as a result of macular edema (20/50 or worse)

• Visual acuity in other eye no worse than 20/200

Exclusion Criteria:

• Known anticipated need for ocular surgery within next 12 months

• History of glaucoma or current high eye pressure requiring more than 1 medication

• Uncontrolled systemic disease

• Known steroid-responder

• Use of systemic steroids - Use of Warfarin/Heparin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Artesia	California	United States
2		Victoria	British Columbia	Canada

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Callanan DG, Gupta S, Boyer DS, Ciulla TA, Singer MA, Kuppermann BD, Liu CC, Li XY, Hollander DA, Schiffman RM, Whitcup SM; Ozurdex PLACID Study Group. Dexamethasone intravitreal implant in combination with laser photocoagulation for the treatment of diffuse diabetic macular edema. Ophthalmology. 2013 Sep;120(9):1843-51. doi: 10.1016/j.ophtha.2013.02.018. Epub 2013 May 22.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT00464685
• Other Study ID Numbers: 206207-012
• First Posted: Apr 24, 2007
• Last Update Posted: Apr 24, 2019
• Last Verified: Apr 1, 2019

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

Study Results

Participant Flow

Arm/Group Title	700 µg Dexamethasone Implant and Laser Photocoagulation	Sham Implant and Laser Photocoagulation
Arm/Group Description	Initial intravitreal injection of 700 µg dexamethasone with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.	Initial sham injection with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.
Period Title: Overall Study
STARTED	126	127
COMPLETED	103	94
NOT COMPLETED	23	33

Baseline Characteristics

Arm/Group Title	700 µg Dexamethasone Implant and Laser Photocoagulation	Sham Implant and Laser Photocoagulation	Total
Arm/Group Description	Initial intravitreal injection of 700 µg dexamethasone with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.	Initial sham injection with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.	Total of all reporting groups
Overall Participants	126	127	253
Age, Customized (Number) [Number]
<45 years	7 5.6%	3 2.4%	10 4%
45 to 65 years	72 57.1%	84 66.1%	156 61.7%
>65 years	47 37.3%	40 31.5%	87 34.4%
Sex: Female, Male (Count of Participants)
Female	64 50.8%	61 48%	125 49.4%
Male	62 49.2%	66 52%	128 50.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With at Least 10 Letters of Improvement in Best Corrected Visual Acuity (BCVA) From Baseline in the Study Eye
Description	BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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 indicates improvement and a decrease in the number of letters read correctly indicates a worsening.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Intent to Treat: all randomized patients

Arm/Group Title	700 µg Dexamethasone Implant and Laser Photocoagulation	Sham Implant and Laser Photocoagulation
Arm/Group Description	Initial intravitreal injection of 700 µg dexamethasone with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.	Initial sham injection with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.
Measure Participants	126	127
Number [Percentage of Patients]	27.8	23.6

2. Secondary Outcome

Title	Change From Baseline in BCVA in the Study Eye
Description	BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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 indicates improvement and a decrease in the number of letters read correctly indicates a worsening.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Intent to Treat: all randomized patients

Arm/Group Title	700 µg Dexamethasone Implant and Laser Photocoagulation	Sham Implant and Laser Photocoagulation
Arm/Group Description	Initial intravitreal injection of 700 µg dexamethasone with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.	Initial sham injection with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.
Measure Participants	126	127
Baseline	57.6 (9.38)	57.8 (9.66)
Change from Baseline at Month 12	2.9 (11.45)	2.1 (12.05)

3. Secondary Outcome

Title	Change From Baseline in Central Subfield Retinal Thickness in the Study Eye
Description	Central subfield retinal thickness is assessed in the study eye by Optical Coherence Tomography (OCT). The central subfield is an area in the retina (back of the eye). OCT is a laser-based, noninvasive, diagnostic system that provides high-resolution, three-dimensional images of the retina from which retinal thickness can be measured. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Intent to Treat: all randomized patients

Arm/Group Title	700 µg Dexamethasone Implant and Laser Photocoagulation	Sham Implant and Laser Photocoagulation
Arm/Group Description	Initial intravitreal injection of 700 µg dexamethasone with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.	Initial sham injection with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.
Measure Participants	126	127
Baseline	438.4 (133.93)	430.3 (131.15)
Change from Baseline at Month 12	-102.8 (130.86)	-125.3 (123.38)

4. Secondary Outcome

Title	Change From Baseline in the Focal Leakage Area in the Study Eye
Description	Focal leakage area in the study eye is assessed using fluorescein angiography. A positive number change from baseline indicates a worsening and a negative number change from baseline indicates an improvement.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Intent to Treat: all randomized patients

Arm/Group Title	700 µg Dexamethasone Implant and Laser Photocoagulation	Sham Implant and Laser Photocoagulation
Arm/Group Description	Initial intravitreal injection of 700 µg dexamethasone with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.	Initial sham injection with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.
Measure Participants	126	127
Baseline	0.6 (1.46)	1.1 (2.64)
Change from Baseline at Month 12	-0.2 (0.96)	-0.7 (3.07)

5. Secondary Outcome

Title	Time to Retreatment in the Study Eye
Description	Time to retreatment in the study eye is defined as the number of days between the initial treatment and re-treatment with the study medication.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

Intent to Treat: all randomized patients

Arm/Group Title	700 µg Dexamethasone Implant and Laser Photocoagulation	Sham Implant and Laser Photocoagulation
Arm/Group Description	Initial intravitreal injection of 700 µg dexamethasone with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.	Initial sham injection with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.
Measure Participants	126	127
Median (95% Confidence Interval) [Days]	189	196

Adverse Events

Adverse Event Reporting Description	The Safety Population was used to assess all serious adverse events (SAEs) and adverse events (AEs) and included all patients who were randomized and treated.
Arm/Group Title	700 µg Dexamethasone Implant and Laser Photocoagulation		Sham Implant and Laser Photocoagulation
Arm/Group Description	Initial intravitreal injection of 700 µg dexamethasone with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.		Initial sham injection with up to 1 additional treatment based on re-treatment criteria. Initial laser photocoagulation with up to 3 additional treatments based on re-treatment criteria.
All Cause Mortality
	700 µg Dexamethasone Implant and Laser Photocoagulation		Sham Implant and Laser Photocoagulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	700 µg Dexamethasone Implant and Laser Photocoagulation		Sham Implant and Laser Photocoagulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/125 (18.4%)		27/127 (21.3%)
Blood and lymphatic system disorders
Haemorrhagic Anaemia	1/125 (0.8%)		0/127 (0%)
Anaemia	0/125 (0%)		2/127 (1.6%)
Cardiac disorders
Coronary Artery Disease	2/125 (1.6%)		0/127 (0%)
Cardiac Failure Congestive	1/125 (0.8%)		2/127 (1.6%)
Myocardial Infarction	0/125 (0%)		2/127 (1.6%)
Atrial Fibrillation	0/125 (0%)		1/127 (0.8%)
Cardiac Failure	0/125 (0%)		1/127 (0.8%)
Cardio-respiratory Arrest	0/125 (0%)		1/127 (0.8%)
Eye disorders
Vitreous Haemorrhage	1/125 (0.8%)		0/127 (0%)
Gastrointestinal disorders
Diarrhoea	1/125 (0.8%)		0/127 (0%)
Gastrointestinal Haemorrhage	1/125 (0.8%)		0/127 (0%)
Gastrooesophageal Reflux Disease	1/125 (0.8%)		0/127 (0%)
Inguinal Hernia, Obstructive	1/125 (0.8%)		0/127 (0%)
Gastrointestinal Necrosis	0/125 (0%)		1/127 (0.8%)
Vomiting	0/125 (0%)		1/127 (0.8%)
General disorders
Chest Pain	1/125 (0.8%)		0/127 (0%)
Hepatobiliary disorders
Cholecystitis	1/125 (0.8%)		0/127 (0%)
Cholecystitis Acute	0/125 (0%)		1/127 (0.8%)
Infections and infestations
Pneumonia	2/125 (1.6%)		1/127 (0.8%)
Diabetic Foot Infection	1/125 (0.8%)		0/127 (0%)
Osteomyelitis	1/125 (0.8%)		0/127 (0%)
Staphylococcal Infection	1/125 (0.8%)		0/127 (0%)
Urinary Tract Infection	1/125 (0.8%)		0/127 (0%)
Gangrene	0/125 (0%)		3/127 (2.4%)
Bronchitis	0/125 (0%)		1/127 (0.8%)
Cellulitis	0/125 (0%)		1/127 (0.8%)
Diverticulitis	0/125 (0%)		1/127 (0.8%)
Incision Site Infection	0/125 (0%)		1/127 (0.8%)
Injury, poisoning and procedural complications
Dialysis Disequilibrium Syndrome	1/125 (0.8%)		0/127 (0%)
Femur Fracture	1/125 (0.8%)		0/127 (0%)
Hip Fracture	1/125 (0.8%)		0/127 (0%)
Joint Dislocation	1/125 (0.8%)		0/127 (0%)
Procedural Pain	1/125 (0.8%)		0/127 (0%)
Ankle Fracture	0/125 (0%)		1/127 (0.8%)
Skull Fracture	0/125 (0%)		1/127 (0.8%)
Metabolism and nutrition disorders
Hypoglycaemic Seizure	1/125 (0.8%)		0/127 (0%)
Hyponatraemia	1/125 (0.8%)		0/127 (0%)
Failure to Thrive	0/125 (0%)		1/127 (0.8%)
Hyperglycaemia	0/125 (0%)		1/127 (0.8%)
Obesity	0/125 (0%)		1/127 (0.8%)
Musculoskeletal and connective tissue disorders
Neuropathic Arthropathy	2/125 (1.6%)		0/127 (0%)
Osteoarthritis	2/125 (1.6%)		0/127 (0%)
Intervertebral Disc Degeneration	1/125 (0.8%)		1/127 (0.8%)
Cervical Spinal Stenosis	0/125 (0%)		1/127 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Neoplasm Malignant	1/125 (0.8%)		1/127 (0.8%)
Basal Cell Carcinoma	1/125 (0.8%)		0/127 (0%)
Hepatic Neoplasm Malignant	1/125 (0.8%)		0/127 (0%)
Squamous Cell Carcinoma	1/125 (0.8%)		0/127 (0%)
Benign Neoplasm of Thyroid Gland	0/125 (0%)		1/127 (0.8%)
Nervous system disorders
Cerebrovascular Accident	1/125 (0.8%)		1/127 (0.8%)
Transient Ischaemic Attack	0/125 (0%)		2/127 (1.6%)
Dementia Alzheimer's Type	0/125 (0%)		1/127 (0.8%)
Renal and urinary disorders
Renal Failure	1/125 (0.8%)		1/127 (0.8%)
Renal Failure Acute	1/125 (0.8%)		0/127 (0%)
Bladder Neck Obstruction	0/125 (0%)		1/127 (0.8%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	1/125 (0.8%)		2/127 (1.6%)
Dyspnoea	0/125 (0%)		1/127 (0.8%)
Skin and subcutaneous tissue disorders
Hypoaesthesia Facial	1/125 (0.8%)		0/127 (0%)
Vascular disorders
Aortic Stenosis	1/125 (0.8%)		0/127 (0%)
Hypertension	0/125 (0%)		1/127 (0.8%)
Hypotension	0/125 (0%)		1/127 (0.8%)
Other (Not Including Serious) Adverse Events
	700 µg Dexamethasone Implant and Laser Photocoagulation		Sham Implant and Laser Photocoagulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	125/125 (100%)		127/127 (100%)
Eye disorders
Conjunctival Haemorrhage	27/125 (21.6%)		24/127 (18.9%)
Vitreous Haemorrhage	17/125 (13.6%)		10/127 (7.9%)
Visual Acuity Reduced	14/125 (11.2%)		18/127 (14.2%)
Cataract	14/125 (11.2%)		8/127 (6.3%)
Eye Pain	13/125 (10.4%)		11/127 (8.7%)
Vitreous Floaters	13/125 (10.4%)		10/127 (7.9%)
Macular Oedema	11/125 (8.8%)		9/127 (7.1%)
Maculopathy	9/125 (7.2%)		8/127 (6.3%)
Vitreous Detachment	9/125 (7.2%)		3/127 (2.4%)
Retinal Exudates	8/125 (6.4%)		7/127 (5.5%)
Diabetic Retinal Oedema	7/125 (5.6%)		11/127 (8.7%)
Retinal Haemorrhage	7/125 (5.6%)		8/127 (6.3%)
Vision Blurred	7/125 (5.6%)		8/127 (6.3%)
General disorders
Oedema Peripheral	3/125 (2.4%)		8/127 (6.3%)
Infections and infestations
Bronchitis	8/125 (6.4%)		5/127 (3.9%)
Upper Respiratory Infection	5/125 (4%)		7/127 (5.5%)
Investigations
Intraocular Pressure Increased	28/125 (22.4%)		8/127 (6.3%)
Nervous system disorders
Headache	3/125 (2.4%)		9/127 (7.1%)
Vascular disorders
Hypertension	10/125 (8%)		8/127 (6.3%)

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.