Safety and Efficacy Study of Dexamethasone Versus Ranibizumab in Patients With Diabetic Macular Edema

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01492400
• Collaborator: (none)
• Enrollment: 363
• Locations: 13
• Arms: 2
• Actual Duration (Months): 23.2
• Patients Per Site: 27.9
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This study will compare the safety and efficacy of the 700 ug dexamethasone intravitreal implant with ranibizumab 0.5 mg intravitreal injections in patients with diabetic macular edema (DME).

Condition or Disease	Intervention/Treatment	Phase
Macular Edema	Drug: dexamethasone Intravitreal Implant; Drug: ranibizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 363 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Actual Study Start Date: Mar 9, 2012
• Actual Primary Completion Date: Feb 13, 2014
• Actual Study Completion Date: Feb 13, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dexamethasone Intravitreal Implant Injection of 700 ug dexamethasone intravitreal implant into the study eye on Day 1, Month 5, and Month 10.	Drug: dexamethasone Intravitreal Implant; Injection of 700 ug dexamethasone intravitreal implant into the study eye on Day 1, Month 5, and Month 10.; Other Names: Ozurdex®
Active Comparator: ranibizumab Injection of ranibizumab 0.5 mg into the study eye on Day 1. Patients may receive additional injections on a monthly basis, as needed, for disease progression.	Drug: ranibizumab; Injection of ranibizumab 0.5 mg into the study eye on Day 1. Patients may receive additional injections on a monthly basis, as needed, for disease progression.; Other Names: Lucentis®

Outcome Measures

Primary Outcome Measures

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

   BCVA is measured using an eye chart and is reported as the number of letters read correctly (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). The average BCVA is calculated across study visits for each patient. A positive number change from baseline indicates an improvement and a negative number change from baseline indicates a worsening.

Secondary Outcome Measures

1. Change From Baseline in Foveal Thickness Measured by Optical Coherence Tomography (OCT) in the Study Eye [Baseline, Month 12]

   OCT is a laser based non-invasive diagnostic system providing high-resolution imaging sections of the fovea (part of the retina) in the study eye after pupil dilation. A negative change from baseline indicates an improvement (less foveal thickness) and a positive change from baseline indicates a worsening (more foveal thickness).

2. Change From Baseline in Total Area of Macular Leakage in the Study Eye Measured on Fluorescein Angiography (FA) [Baseline, Month 12]

   FA is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. A negative change from baseline indicates a decrease in leakage (improvement) and a positive change from baseline indicates an increase in leakage (worsening).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of type 1 or 2 diabetes mellitus

• Diagnosis of macular edema

• Visual acuity between 20/200 to 20/40

Exclusion Criteria:

• Eye surgery to the study eye within 3 months

• Use of Ozurdex® within 9 months

• Any active ocular inflammation and infection

• Diagnosis of glaucoma

• Use of anti-VEGF treatment (e.g., Lucentis®) within 3 months in the eye or systemic use (e.g., Avastin®) within 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Arlington	Texas	United States
2		Brussels		Belgium
3		Copenhagen		Denmark
4		Glostrup		Denmark
5		Paris		France
6		Ahaus		Germany
7		Tel Aviv		Israel
8		Udine		Italy
9		Nijmegen		Netherlands
10		Coimbra		Portugal
11		Pretoria		South Africa
12		Barcelona		Spain
13		London	England	United Kingdom

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Callanan DG, Loewenstein A, Patel SS, Massin P, Corcóstegui B, Li XY, Jiao J, Hashad Y, Whitcup SM. A multicenter, 12-month randomized study comparing dexamethasone intravitreal implant with ranibizumab in patients with diabetic macular edema. Graefes Arch Clin Exp Ophthalmol. 2017 Mar;255(3):463-473. doi: 10.1007/s00417-016-3472-1. Epub 2016 Sep 8.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01492400
• Other Study ID Numbers: 206207-024
• First Posted: Dec 15, 2011
• Last Update Posted: Apr 17, 2019
• Last Verified: Apr 1, 2019

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

Study Results

Participant Flow

Arm/Group Title	Dexamethasone Intravitreal Implant	Ranibizumab
Arm/Group Description	Injection of 700 ug dexamethasone intravitreal implant into the study eye on Day 1, Month 5, and Month 10.	Injection of ranibizumab 0.5 mg into the study eye on Day 1. Patients may receive additional injections on a monthly basis, as needed, for disease progression.
Period Title: Overall Study
STARTED	181	182
COMPLETED	165	166
NOT COMPLETED	16	16

Baseline Characteristics

Arm/Group Title	Dexamethasone Intravitreal Implant	Ranibizumab	Total
Arm/Group Description	Injection of 700 ug dexamethasone intravitreal implant into the study eye on Day 1, Month 5, and Month 10.	Injection of ranibizumab 0.5 mg into the study eye on Day 1. Patients may receive additional injections on a monthly basis, as needed, for disease progression.	Total of all reporting groups
Overall Participants	181	182	363
Age, Customized (Number) [Number]
<45 years	5 2.8%	5 2.7%	10 2.8%
45 to 65 years	102 56.4%	96 52.7%	198 54.5%
>65 years	74 40.9%	81 44.5%	155 42.7%
Sex: Female, Male (Count of Participants)
Female	69 38.1%	66 36.3%	135 37.2%
Male	112 61.9%	116 63.7%	228 62.8%

Outcome Measures

1. Primary Outcome

Title	Average Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
Description	BCVA is measured using an eye chart and is reported as the number of letters read correctly (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). The average BCVA is calculated across study visits for each patient. A positive number change from baseline indicates an improvement and a negative number change from baseline indicates a worsening.
Time Frame	Baseline, 12 Months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients

Arm/Group Title	Dexamethasone Intravitreal Implant	Ranibizumab
Arm/Group Description	Injection of 700 ug dexamethasone intravitreal implant into the study eye on Day 1, Month 5, and Month 10.	Injection of ranibizumab 0.5 mg into the study eye on Day 1. Patients may receive additional injections on a monthly basis, as needed, for disease progression.
Measure Participants	181	182
Baseline	60.2 (9.74)	60.4 (9.34)
Change from Baseline at 12 Months	4.34 (7.342)	7.60 (6.735)

2. Secondary Outcome

Title	Change From Baseline in Foveal Thickness Measured by Optical Coherence Tomography (OCT) in the Study Eye
Description	OCT is a laser based non-invasive diagnostic system providing high-resolution imaging sections of the fovea (part of the retina) in the study eye after pupil dilation. A negative change from baseline indicates an improvement (less foveal thickness) and a positive change from baseline indicates a worsening (more foveal thickness).
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients

Arm/Group Title	Dexamethasone Intravitreal Implant	Ranibizumab
Arm/Group Description	Injection of 700 ug dexamethasone intravitreal implant into the study eye on Day 1, Month 5, and Month 10.	Injection of ranibizumab 0.5 mg into the study eye on Day 1. Patients may receive additional injections on a monthly basis, as needed, for disease progression.
Measure Participants	181	182
Baseline	465.1 (136.09)	471.2 (139.51)
Change from Baseline at Month 12 (N=163, 166)	-173.9 (129.64)	-163.5 (161.34)

3. Secondary Outcome

Title	Change From Baseline in Total Area of Macular Leakage in the Study Eye Measured on Fluorescein Angiography (FA)
Description	FA is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. A negative change from baseline indicates a decrease in leakage (improvement) and a positive change from baseline indicates an increase in leakage (worsening).
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients

Arm/Group Title	Dexamethasone Intravitreal Implant	Ranibizumab
Arm/Group Description	Injection of 700 ug dexamethasone intravitreal implant into the study eye on Day 1, Month 5, and Month 10.	Injection of ranibizumab 0.5 mg into the study eye on Day 1. Patients may receive additional injections on a monthly basis, as needed, for disease progression.
Measure Participants	172	177
Baseline	19.2 (13.01)	18.9 (12.55)
Change from Baseline at Month 12 (N=125, 142)	-16.1 (11.64)	-12.0 (10.54)

Adverse Events

Adverse Event Reporting Description	Treatment emergent adverse events (TEAE) are reported and include all adverse events (AEs) and serious adverse events (SAEs) that began or worsened after study treatment.
Arm/Group Title	Dexamethasone Intravitreal Implant		Ranibizumab
Arm/Group Description	Injection of 700 ug dexamethasone intravitreal implant into the study eye on Day 1, Month 5, and Month 10.		Injection of ranibizumab 0.5 mg into the study eye on Day 1. Patients may receive additional injections on a monthly basis, as needed, for disease progression.
All Cause Mortality
	Dexamethasone Intravitreal Implant		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dexamethasone Intravitreal Implant		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/181 (22.1%)		41/182 (22.5%)
Blood and lymphatic system disorders
Anaemia	1/181 (0.6%)		2/182 (1.1%)
Leukocytosis	1/181 (0.6%)		0/182 (0%)
Cardiac disorders
Cardiac Failure Congestive	4/181 (2.2%)		1/182 (0.5%)
Coronary Artery Disease	2/181 (1.1%)		2/182 (1.1%)
Angina Pectoris	1/181 (0.6%)		2/182 (1.1%)
Atrial Fibrillation	1/181 (0.6%)		1/182 (0.5%)
Cardiac Failure	1/181 (0.6%)		1/182 (0.5%)
Acute Myocardial Infarction	1/181 (0.6%)		0/182 (0%)
Myocardial Infarction	1/181 (0.6%)		0/182 (0%)
Pericardial Effusion	1/181 (0.6%)		0/182 (0%)
Pericarditis	1/181 (0.6%)		0/182 (0%)
Myocardial Ischaemia	0/181 (0%)		2/182 (1.1%)
Aortic Valve Stenosis	0/181 (0%)		1/182 (0.5%)
Palpitations	0/181 (0%)		1/182 (0.5%)
Ventricular Tachyarrhythmia	0/181 (0%)		1/182 (0.5%)
Ear and labyrinth disorders
Sudden Hearing Loss	0/181 (0%)		1/182 (0.5%)
Eye disorders
Open Angle Glaucoma	1/181 (0.6%)		0/182 (0%)
Choroiditis	0/181 (0%)		1/182 (0.5%)
Lacrimation Increased	0/181 (0%)		1/182 (0.5%)
Vitreous Haemorrhage	0/181 (0%)		1/182 (0.5%)
Gastrointestinal disorders
Colitis	1/181 (0.6%)		0/182 (0%)
Duodenal Ulcer Haemorrhage	1/181 (0.6%)		0/182 (0%)
Inguinal Hernia	1/181 (0.6%)		0/182 (0%)
Abdominal Pain	0/181 (0%)		2/182 (1.1%)
Nausea	0/181 (0%)		1/182 (0.5%)
Upper Gastrointestinal Haemorrhage	0/181 (0%)		1/182 (0.5%)
Vomiting	0/181 (0%)		1/182 (0.5%)
General disorders
Chest Pain	2/181 (1.1%)		0/182 (0%)
Asthenia	1/181 (0.6%)		0/182 (0%)
Local Swelling	1/181 (0.6%)		0/182 (0%)
Pyrexia	0/181 (0%)		2/182 (1.1%)
Generalised Oedema	0/181 (0%)		1/182 (0.5%)
Oedema	0/181 (0%)		1/182 (0.5%)
Hepatobiliary disorders
Jaundice	0/181 (0%)		1/182 (0.5%)
Infections and infestations
Sepsis	2/181 (1.1%)		2/182 (1.1%)
Cellulitis	1/181 (0.6%)		1/182 (0.5%)
Endophthalmitis	1/181 (0.6%)		1/182 (0.5%)
Pneumonia	1/181 (0.6%)		1/182 (0.5%)
Wound Infection	1/181 (0.6%)		1/182 (0.5%)
Abscess Limb	1/181 (0.6%)		0/182 (0%)
Anal Abscess	1/181 (0.6%)		0/182 (0%)
Gastroenteritis	1/181 (0.6%)		0/182 (0%)
Kidney Infection	1/181 (0.6%)		0/182 (0%)
Pyelonephritis	1/181 (0.6%)		0/182 (0%)
Sialoadenitis	1/181 (0.6%)		0/182 (0%)
Abdominal Wall Abscess	0/181 (0%)		1/182 (0.5%)
Atypical Pneumonia	0/181 (0%)		1/182 (0.5%)
Infected Bites	0/181 (0%)		1/182 (0.5%)
Septic Shock	0/181 (0%)		1/182 (0.5%)
Injury, poisoning and procedural complications
Hip Fracture	2/181 (1.1%)		0/182 (0%)
Post Procedural Haemorrhage	1/181 (0.6%)		0/182 (0%)
Spinal Fracture	1/181 (0.6%)		0/182 (0%)
Tendon Rupture	1/181 (0.6%)		0/182 (0%)
Femoral Neck Fracture	0/181 (0%)		1/182 (0.5%)
Hand Fracture	0/181 (0%)		1/182 (0.5%)
Humerus Fracture	0/181 (0%)		1/182 (0.5%)
Post Procedural Haematoma	0/181 (0%)		1/182 (0.5%)
Investigations
Intraocular Pressure Increased	2/181 (1.1%)		0/182 (0%)
Weight Decreased	0/181 (0%)		1/182 (0.5%)
Metabolism and nutrition disorders
Hypoglycaemia	2/181 (1.1%)		1/182 (0.5%)
Hyperglycaemia	1/181 (0.6%)		0/182 (0%)
Diabetes Mellitus Inadequate Control	0/181 (0%)		2/182 (1.1%)
Dehydration	0/181 (0%)		1/182 (0.5%)
Hypokalaemia	0/181 (0%)		1/182 (0.5%)
Metabolic Acidosis	0/181 (0%)		1/182 (0.5%)
Type 2 Diabetes Mellitus	0/181 (0%)		1/182 (0.5%)
Musculoskeletal and connective tissue disorders
Rotator Cuff Syndrome	1/181 (0.6%)		0/182 (0%)
Osteonecrosis	0/181 (0%)		1/182 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	3/181 (1.7%)		0/182 (0%)
Bladder Transitional Cell Carcinoma	1/181 (0.6%)		0/182 (0%)
Lung Squamous Cell Carcinoma Metastatic	1/181 (0.6%)		0/182 (0%)
Mantle Cell Lymphoma	1/181 (0.6%)		0/182 (0%)
Neoplasm Malignant	1/181 (0.6%)		0/182 (0%)
Prostate Cancer	1/112 (0.9%)		0/116 (0%)
Squamous Cell Carcinoma of the Tongue	1/181 (0.6%)		0/182 (0%)
Colon Cancer	0/181 (0%)		1/182 (0.5%)
Pancreatic Carcinoma	0/181 (0%)		1/182 (0.5%)
Squamous Cell Carcinoma	0/181 (0%)		1/182 (0.5%)
Nervous system disorders
Syncope	2/181 (1.1%)		0/182 (0%)
Grand Mal Convulsion	1/181 (0.6%)		0/182 (0%)
Meningorrhagia	1/181 (0.6%)		0/182 (0%)
Cerebrovascular Accident	0/181 (0%)		1/182 (0.5%)
Convulsion	0/181 (0%)		1/182 (0.5%)
Haemorrhagic Stroke	0/181 (0%)		1/182 (0.5%)
Transient Ischaemic Attack	0/181 (0%)		1/182 (0.5%)
Renal and urinary disorders
Renal Failure Acute	4/181 (2.2%)		3/182 (1.6%)
Renal Failure Chronic	1/181 (0.6%)		1/182 (0.5%)
Nephrolithiasis	1/181 (0.6%)		0/182 (0%)
Nephropathy	0/181 (0%)		1/182 (0.5%)
Renal Failure	0/181 (0%)		1/182 (0.5%)
Reproductive system and breast disorders
Endometrial Hyperplasia	0/69 (0%)		1/66 (1.5%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	2/181 (1.1%)		1/182 (0.5%)
Chronic Obstructive Pulmonary Disease	1/181 (0.6%)		0/182 (0%)
Dyspnoea	1/181 (0.6%)		0/182 (0%)
Respiratory Depression	1/181 (0.6%)		0/182 (0%)
Pulmonary Oedema	0/181 (0%)		1/182 (0.5%)
Skin and subcutaneous tissue disorders
Diabetic Foot	1/181 (0.6%)		1/182 (0.5%)
Surgical and medical procedures
Cardiac Pacemaker Insertion	1/181 (0.6%)		0/182 (0%)
Liposuction	1/181 (0.6%)		0/182 (0%)
Vascular disorders
Orthostatic Hypotension	1/181 (0.6%)		0/182 (0%)
Hypertensive Crisis	0/181 (0%)		1/182 (0.5%)
Peripheral Ischaemia	0/181 (0%)		1/182 (0.5%)
Peripheral Vascular Disorder	0/181 (0%)		1/182 (0.5%)
Other (Not Including Serious) Adverse Events
	Dexamethasone Intravitreal Implant		Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	160/181 (88.4%)		104/182 (57.1%)
Blood and lymphatic system disorders
Anaemia	6/181 (3.3%)		10/182 (5.5%)
Eye disorders
Conjunctival Haemorrhage	36/181 (19.9%)		24/182 (13.2%)
Cataract	28/181 (15.5%)		8/182 (4.4%)
Vitreous Haemorrhage	22/181 (12.2%)		7/182 (3.8%)
Visual Acuity Reduced	14/181 (7.7%)		5/182 (2.7%)
Cataract Subcapsular	14/181 (7.7%)		1/182 (0.5%)
Vitreous Floaters	13/181 (7.2%)		2/182 (1.1%)
Ocular Hypertension	11/181 (6.1%)		2/182 (1.1%)
Eye Pain	10/181 (5.5%)		6/182 (3.3%)
Diabetic Retinal Oedema	10/181 (5.5%)		5/182 (2.7%)
Vitreous Detachment	10/181 (5.5%)		5/182 (2.7%)
Punctate Keratitis	9/181 (5%)		3/182 (1.6%)
Macular Oedema	3/181 (1.7%)		10/182 (5.5%)
Infections and infestations
Influenza	9/181 (5%)		4/182 (2.2%)
Investigations
Intraocular Pressure Increased	65/181 (35.9%)		12/182 (6.6%)

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.