Ranibizumab for Treatment of Persistent Diabetic Neovascularization Assessed by Wide-Field Imaging

• Sponsor: Rush University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00606138
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 8
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Diabetic neovascularization refers to a type of diabetic retinopathy which is worsening by the abnormal growth of blood vessels in the back of the eye, damaging the retina. The usual treatment is a type of laser, called panretinal photocoagulation. One drawback is that the amount of space within the eye for use of this treatment eventually has its limit, and should not be used too near the part of the retina used for detailed vision (the macula). In similar eye disorders, there are certain injectable medications called anti-VEGF treatments which can slow down or stop this abnormal blood vessel growth. This study sought to compare use of ranibizumab versus standard panretinal photocoagulation in treatment of diabetic neovascularization.

Condition or Disease	Intervention/Treatment	Phase
Proliferative Diabetic Retinopathy	Drug: ranibizumab; Procedure: Laser photocoagulation	Phase 1/Phase 2

Detailed Description

The purpose is to compare the efficacy of ranibizumab versus additional panretinal photocoagulation on diabetic neovascularization that is persistent despite previous treatment with panretinal photocoagulation. We hypothesize that ranibizumab intravitreal injections would induce neovascular regression in similar or better fashion than supplemental laser photocoagulation. Consented, enrolled subjects will either receive open-label intravitreal injections of 0.5-mg dose of ranibizumab or additional panretinal photocoagulation (up to 500 300-500 um laser spots) in a ratio of two-to-one (2:1) at the beginning of the study period. ETDRS best-corrected visual acuity, contrast sensitivity, and Optos color photography will be performed at enrollment, at weeks 1, 2, 3 and 4, and at months 2, 3, 4, 5 and 6. The subjects will undergo fluorescein angiography utilizing the Optomap FA (fluorescein angiography) system and optical coherence tomography (OCT) at enrollment, at weeks 2 and 4, and at months 2, 3, 4 and 6. The subjects will be followed for a 6-month period for stabilization, regression, or recurrence of neovascularization. In addition, patients will be evaluated for occurrence of macular edema.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Investigation of Ranibizumab for the Treatment of Persistent Diabetic Neovascularization as Assessed by Super Wide-Field Angiography (Optos)
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anti-VEGF injection Intravitreal injection of 0.5-mg dose of ranibizumab	Drug: ranibizumab; One 0.5 mg intravitreal injection; Other Names: Lucentis
Active Comparator: PRP Laser Additional panretinal photocoagulation (up to 500 300-500 um laser spots)	Procedure: Laser photocoagulation; panretinal photocoagulation (up to 500 300-500 um laser spots)

Outcome Measures

Primary Outcome Measures

1. The Mean Percentage Change of the Area of the Patient's Neovascularization as Measured in Pixels by Optomap FA (Fluorescein Angiography) [Week 4; Month 6]

   This is a measurement of how much change in neovascularization has occurred, using the Optomap FA readings to calculate the increase or decrease in surface area of the retina that is affected by neovascularization.

2. The Mean Percentage Change of Macular Edema Measured by Retinal Thickness by OCT (Optical Coherence Tomography) [Week 4; Month 6]

3. Incidence and Severity of Ocular Adverse Events, as Identified by Ophthalmic Examination [Month 6]

4. Incidence and Severity of Other Adverse Events, as Identified by Physical Examination, Subject Reporting, and Changes in Vital Signs [Week 1, 2, 4; Month 2, 3, 4, 5, 6]

Secondary Outcome Measures

1. Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Letters Read Correctly on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters [Week 4; Month 6]

2. Percentage of Patients Gaining 3 or More Lines of Vision According to ETDRS Eye Chart Testing [Week 1, 2, 4; Month 2, 3, 4, 5, 6]

3. Occurrence Rate of Proliferative Diabetic Complications Including Vitreous Hemorrhage, Iris Neovascularization, and Tractional Retinal Detachment [Month 6]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study

• Age 18 years or older

Patient related considerations:

• Patients with Diabetes Mellitus (Type I or II) are eligible. HgA1c will be evaluated at the beginning of the study, but this value will have no significance in inclusion or exclusion.

• Patients will not be pregnant at enrollment and must provide evidence of the use of two types of birth control while enrolled in the study.

• Patients will have no known sensitivity to ranibizumab or other anti-VEGF injections.

Disease related considerations:

• Patients will have diabetic neovascularization as seen on fluorescein angiography that was previously treated with full (at least 1200 laser burns) panretinal photocoagulation and that has persisted at least three months.

• There will be no evidence of ocular inflammation at enrollment.

• There is no restriction on patient's current medications or concomitant illnesses as long as there is no interference with patient follow-up.

Other considerations:

• Patients may not be enrolled in another clinical study or observational trial.

• There is no limitation on patient's institutional status as long as the patient is able to participate in follow-up.

Exclusion Criteria:

• Pregnancy (positive pregnancy test)

• Uncontrolled glaucoma on three medicines or more to control intraocular pressure

• Prior enrollment in the study

• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated

• Participation in another simultaneous medical investigation or trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush University Medical Center	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• Rush University Medical Center
• Genentech, Inc.

Investigators

• Principal Investigator: Mathew W MacCumber, MD, PhD, Rush University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rush University Medical Center
• ClinicalTrials.gov Identifier: NCT00606138
• Other Study ID Numbers: 06120402
• First Posted: Feb 1, 2008
• Last Update Posted: Nov 6, 2014
• Last Verified: Nov 1, 2014

• Additional relevant MeSH terms: Diabetic Retinopathy; Neovascularization, Pathologic; Ranibizumab

Study Results

Participant Flow

Recruitment Details	Subjects will be recruited starting in 2007 and until sufficient subject population is reached. They will be seen in an eye clinic at Rush University Medical Center.
Pre-assignment Detail	There is no wash-out period. Recruited subjects must be in need of treatment for their PDR, and will be randomized and treated at the baseline visit.

Arm/Group Title	1 - Ranibizumab	2 - Additional PRP Treatment
Arm/Group Description	Intravitreal injection of 0.5-mg dose of ranibizumab	Additional panretinal photocoagulation (up to 500 300-500 um laser spots)
Period Title: Overall Study
STARTED	6	2
COMPLETED	6	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	1 - Ranibizumab	2 - Additional PRP Treatment	Total
Arm/Group Description	Intravitreal injection of 0.5-mg dose of ranibizumab	Additional panretinal photocoagulation (up to 500 300-500 um laser spots)	Total of all reporting groups
Overall Participants	6	2	8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	1 50%	7 87.5%
>=65 years	0 0%	1 50%	1 12.5%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57	67	59
Sex: Female, Male (Count of Participants)
Female	1 16.7%	1 50%	2 25%
Male	5 83.3%	1 50%	6 75%
Region of Enrollment (participants) [Number]
United States	6 100%	2 100%	8 100%

Outcome Measures

1. Primary Outcome

Title	The Mean Percentage Change of the Area of the Patient's Neovascularization as Measured in Pixels by Optomap FA (Fluorescein Angiography)
Description	This is a measurement of how much change in neovascularization has occurred, using the Optomap FA readings to calculate the increase or decrease in surface area of the retina that is affected by neovascularization.
Time Frame	Week 4; Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 - Ranibizumab	2 - Additional PRP Treatment
Arm/Group Description	Intravitreal injection of 0.5-mg dose of ranibizumab	Additional panretinal photocoagulation (up to 500 300-500 um laser spots)
Measure Participants	6	2
Week 4	-84.1 (NA)	52.6 (NA)
Month 6	29.8 (NA)	55.4 (NA)

2. Primary Outcome

Title	The Mean Percentage Change of Macular Edema Measured by Retinal Thickness by OCT (Optical Coherence Tomography)
Time Frame	Week 4; Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 - Ranibizumab	2 - Additional PRP Treatment
Arm/Group Description	Intravitreal injection of 0.5-mg dose of ranibizumab	Additional panretinal photocoagulation (up to 500 300-500 um laser spots)
Measure Participants	6	2
Week 4	-7.2 (NA)	-8.4 (NA)
Month 6	34.5 (NA)	-2.1 (NA)

3. Primary Outcome

Title	Incidence and Severity of Ocular Adverse Events, as Identified by Ophthalmic Examination
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 - Ranibizumab	2 - Additional PRP Treatment
Arm/Group Description	Intravitreal injection of 0.5-mg dose of ranibizumab	Additional panretinal photocoagulation (up to 500 300-500 um laser spots)
Measure Participants	6	2
Number [number of events]	0	1

4. Primary Outcome

Title	Incidence and Severity of Other Adverse Events, as Identified by Physical Examination, Subject Reporting, and Changes in Vital Signs
Time Frame	Week 1, 2, 4; Month 2, 3, 4, 5, 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Mean Change in Best Corrected Visual Acuity (BCVA), as Assessed by the Number of Letters Read Correctly on the ETDRS Eye Chart at a Starting Test Distance of 4 Meters
Time Frame	Week 4; Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 - Ranibizumab	2 - Additional PRP Treatment
Arm/Group Description	Intravitreal injection of 0.5-mg dose of ranibizumab	Additional panretinal photocoagulation (up to 500 300-500 um laser spots)
Measure Participants	6	2
Week 4	2 (1)	0 (1)
Month 6	3 (1.5)	2 (1.5)

6. Secondary Outcome

Title	Percentage of Patients Gaining 3 or More Lines of Vision According to ETDRS Eye Chart Testing
Time Frame	Week 1, 2, 4; Month 2, 3, 4, 5, 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Occurrence Rate of Proliferative Diabetic Complications Including Vitreous Hemorrhage, Iris Neovascularization, and Tractional Retinal Detachment
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 - Ranibizumab	2 - Additional PRP Treatment
Arm/Group Description	Intravitreal injection of 0.5-mg dose of ranibizumab	Additional panretinal photocoagulation (up to 500 300-500 um laser spots)
Measure Participants	6	2
Number [number of PDR complications]	0	1

Adverse Events

Arm/Group Title	1 - Ranibizumab		2 - Additional PRP Treatment
Arm/Group Description	Intravitreal injection of 0.5-mg dose of ranibizumab		Additional panretinal photocoagulation (up to 500 300-500 um laser spots)
All Cause Mortality
	1 - Ranibizumab		2 - Additional PRP Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1 - Ranibizumab		2 - Additional PRP Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	1 - Ranibizumab		2 - Additional PRP Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/2 (50%)
Eye disorders
Eye injury, mild, unrelated to treatment	0/6 (0%)	0	1/2 (50%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.