Aflibercept Injection for Proliferative Diabetic Retinopathy

• Sponsor: University of Oklahoma (Other)
• Overall Status: Completed
• CT.gov ID: NCT01805297
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 32
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

To evaluate the ocular and systemic safety of intravitreal aflibercept injection in patients undergoing Pars Plana Vitrectomy for Proliferative Diabetic Retinopathy.

Condition or Disease	Intervention/Treatment	Phase
Vitreous Hemorrhage	Drug: Intravitreal Aflibercept Injection; Other: Standard Vitrectomy	Phase 2

Detailed Description

Patients who need Pars Plana Vitrectomy surgery, and agree to participate in this study will receive an injection of 2.0mg aflibercept 4 to 6 days before Vitrectomy surgery. Half of these patients will be randomized to receive another injection of 2.0mg aflibercept immediately after their surgery. Postoperative patient visits in this study will be at 1 day, and at weeks 1, 4, 16 and 24, and at any other times as deemed necessary by the Investigator.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intravitreal Aflibercept Injection as a Surgical Adjuvant in Severe Proliferative Diabetic Retinopathy
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Vitrectomy with Aflibercept Injection Preoperative 2.0mg intravitreal aflibercept and vitrectomy with intraoperative 2.0mg intravitreal aflibercept injection.	Drug: Intravitreal Aflibercept Injection; One time 2.0mg aflibercept injection, following pars plana vitrectomy.; Other Names: Eylea
Active Comparator: Standard Vitrectomy Preoperative 2.0mg intravitreal aflibercept and standard of care vitrectomy.	Other: Standard Vitrectomy; Surgical intervention

Outcome Measures

Primary Outcome Measures

1. Rate of Resolved Post-operative Vitreous Hemorrhage. [24 weeks]

   Percentage of patients who had no vitreous hemorrhage before or at week 24

Secondary Outcome Measures

1. Mean Change in Visual Acuity [24 weeks]

   Change in visual acuity measured using "Early Treatment of Diabetic Retinopathy Study" visual acuity charts and letter score difference from baseline to 6 month. A greater number indicates a higher increase in vision from the baseline score. A negative number would indicate that vision decreased.

2. Need for Any Additional Surgical Intervention. [24 weeks]

3. Changes in Mean Central Retinal Thickness. [24 weeks]

   The amount of thickness change in microns from baseline to 6 month visit. A positive number indicates an increase in thickness and a negative number would indicate a decrease in thickness.

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

• Diagnosed with proliferative diabetic retinopathy (PDR) requiring pars plana vitrectomy (PPV)

• Best corrected visual acuity in the study eye between 20/40 to light perception (LP) using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart

Exclusion Criteria:

• Pregnancy (positive urine pregnancy test) or lactation

• Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an intrauterine device (IUD), or contraceptive hormone implant or patch.

• Participation in a study of an investigational drug or device within the past 30 days prior to enrolling in the study

• For previously treated subjects -

• Prior treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy in the study eye within 28 days of Screening

• Prior treatment with triamcinolone in the study eye within 6 months of Screening.

• Prior treatment with dexamethasone in the study eye within 30 days of Screening

• Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Baseline

• History of vitrectomy surgery, submacular surgery, or other surgical intervention for PDR in the study eye

• Active intraocular inflammation (grade trace or above) in the study eye

• History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye

• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye

• Uncontrolled glaucoma in the study eye (defined as intraocular pressure (IOP) ≥ 30 mmHg despite treatment with anti-glaucoma medication)

• History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 6 months of study enrollment.

• History of allergy to fluorescein, indocyanine green (ICG) or iodine, not amenable to treatment

• Presence of macular traction

• Uncontrolled hypertension (e.g., 120/200 mmHg) prior to surgery (PPV)

• Concomitant use of any systemic anti-VEGF therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dean McGee Eye Institute	Oklahoma City	Oklahoma	United States	73104

Sponsors and Collaborators

• University of Oklahoma

Investigators

• Principal Investigator: Robert E Leonard, MD, Dean McGee Eye Institute
• Principal Investigator: Vinay A Shah, MD, Dean McGee Eye Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Oklahoma
• ClinicalTrials.gov Identifier: NCT01805297
• Other Study ID Numbers: VS-12-01
• First Posted: Mar 6, 2013
• Last Update Posted: Sep 13, 2017
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Oklahoma: Proliferative Diabetic Retinopathy
• Additional relevant MeSH terms: Retinal Diseases; Diabetic Retinopathy; Vitreous Hemorrhage; Hemorrhage; Aflibercept

Study Results

Participant Flow

Arm/Group Title	Vitrectomy With Aflibercept Injection	Standard Vitrectomy
Arm/Group Description	Preoperative 2.0mg intravitreal aflibercept and vitrectomy with intraoperative 2.0mg intravitreal aflibercept injection. Intravitreal Aflibercept Injection: One time 2.0mg aflibercept injection, following pars plana vitrectomy.	Preoperative 2.0mg intravitreal aflibercept and standard of care vitrectomy. Standard Vitrectomy: Surgical intervention
Period Title: Overall Study
STARTED	6	6
COMPLETED	4	3
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Vitrectomy With Aflibercept Injection	Standard Vitrectomy	Total
Arm/Group Description	Preoperative 2.0mg intravitreal aflibercept and vitrectomy with intraoperative 2.0mg intravitreal aflibercept injection. Intravitreal Aflibercept Injection: One time 2.0mg aflibercept injection, immediately following pars plana vitrectomy.	Preoperative 2.0mg intravitreal aflibercept and standard of care vitrectomy. Standard Vitrectomy: Surgical intervention	Total of all reporting groups
Overall Participants	6	6	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	5 83.3%	11 91.7%
>=65 years	0 0%	1 16.7%	1 8.3%
Sex: Female, Male (Count of Participants)
Female	3 50%	2 33.3%	5 41.7%
Male	3 50%	4 66.7%	7 58.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 16.7%	1 16.7%	2 16.7%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 16.7%	0 0%	1 8.3%
White	4 66.7%	5 83.3%	9 75%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	6 100%	12 100%
Mean visual acuity (number of letters read on ETDRS Chart) [Mean (Full Range) ]
Mean (Full Range) [number of letters read on ETDRS Chart]	13.8	17.7	15.9
Intraocular pressure (mmHg) [Mean (Full Range) ]
Mean (Full Range) [mmHg]	14	11.2	12.6
Central retinal thickness (Microns) [Mean (Full Range) ]
Mean (Full Range) [Microns]	304	305	304.5

Outcome Measures

1. Primary Outcome

Title	Rate of Resolved Post-operative Vitreous Hemorrhage.
Description	Percentage of patients who had no vitreous hemorrhage before or at week 24
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitrectomy With Aflibercept Injection	Standard Vitrectomy
Arm/Group Description	Preoperative 2.0mg intravitreal aflibercept and vitrectomy with intraoperative 2.0mg intravitreal aflibercept injection. Intravitreal Aflibercept Injection: One time 2.0mg aflibercept injection, following pars plana vitrectomy.	Preoperative 2.0mg intravitreal aflibercept and standard of care vitrectomy. Standard Vitrectomy: Surgical intervention
Measure Participants	6	6
Count of Participants [Participants]	6 100%	5 83.3%

2. Secondary Outcome

Title	Mean Change in Visual Acuity
Description	Change in visual acuity measured using "Early Treatment of Diabetic Retinopathy Study" visual acuity charts and letter score difference from baseline to 6 month. A greater number indicates a higher increase in vision from the baseline score. A negative number would indicate that vision decreased.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Patients who completed 24 week visit

Arm/Group Title	Vitrectomy With Aflibercept Injection	Standard Vitrectomy
Arm/Group Description	Preoperative 2.0mg intravitreal aflibercept and vitrectomy with intraoperative 2.0mg intravitreal aflibercept injection. Intravitreal Aflibercept Injection: One time 2.0mg aflibercept injection, immediately following pars plana vitrectomy.	Preoperative 2.0mg intravitreal aflibercept and standard of care vitrectomy. Standard Vitrectomy: Surgical intervention
Measure Participants	4	3
Mean (Full Range) [Number of letters Read]	56.75	41.67

3. Secondary Outcome

Title	Need for Any Additional Surgical Intervention.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitrectomy With Aflibercept Injection	Standard Vitrectomy
Arm/Group Description	Preoperative 2.0mg intravitreal aflibercept and vitrectomy with intraoperative 2.0mg intravitreal aflibercept injection. Intravitreal Aflibercept Injection: One time 2.0mg aflibercept injection, following pars plana vitrectomy.	Preoperative 2.0mg intravitreal aflibercept and standard of care vitrectomy. Standard Vitrectomy: Surgical intervention
Measure Participants	6	6
Count of Participants [Participants]	0 0%	0 0%

4. Secondary Outcome

Title	Changes in Mean Central Retinal Thickness.
Description	The amount of thickness change in microns from baseline to 6 month visit. A positive number indicates an increase in thickness and a negative number would indicate a decrease in thickness.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Due to lack of clear view due to vitreous Hemorrhage, all but 2 patients were unable to have optical coherence tomography at baseline, and one these was lost to follow up. For this reason, data collected for the few patients who were able to have the test was not analyzed

Arm/Group Title	Vitrectomy With Aflibercept Injection	Standard Vitrectomy
Arm/Group Description	Preoperative 2.0mg intravitreal aflibercept and vitrectomy with intraoperative 2.0mg intravitreal aflibercept injection. Intravitreal Aflibercept Injection: One time 2.0mg aflibercept injection, following pars plana vitrectomy.	Preoperative 2.0mg intravitreal aflibercept and standard of care vitrectomy. Standard Vitrectomy: Surgical intervention
Measure Participants	0	1
Number [Microns]	20

Adverse Events

Time Frame	6 months
Arm/Group Title	Vitrectomy With Aflibercept Injection		Standard Vitrectomy
Arm/Group Description	Preoperative 2.0mg intravitreal aflibercept and vitrectomy with intraoperative 2.0mg intravitreal aflibercept injection. Intravitreal Aflibercept Injection: One time 2.0mg aflibercept injection, following pars plana vitrectomy.		Preoperative 2.0mg intravitreal aflibercept and standard of care vitrectomy. Standard Vitrectomy: Surgical intervention
All Cause Mortality
	Vitrectomy With Aflibercept Injection		Standard Vitrectomy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Vitrectomy With Aflibercept Injection		Standard Vitrectomy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Vitrectomy With Aflibercept Injection		Standard Vitrectomy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		5/6 (83.3%)
Eye disorders
Post operative ocular pain	3/6 (50%)	3	4/6 (66.7%)	4
descemet's folds	0/6 (0%)	0	1/6 (16.7%)	1
Subconjunctival Hemorrhage	2/6 (33.3%)	2	1/6 (16.7%)	1
vitreous haze	1/6 (16.7%)	1	0/6 (0%)	0
cataract	0/6 (0%)	0	1/6 (16.7%)	1
Optic disc pallor	0/6 (0%)	0	1/6 (16.7%)	1
visual disturbance	1/6 (16.7%)	1	0/6 (0%)	0
vitreous hemorrhage	1/6 (16.7%)	1	0/6 (0%)	0
photophobia	1/6 (16.7%)	1	0/6 (0%)	0
ocular irritation	0/6 (0%)	0	1/6 (16.7%)	1
Gastrointestinal disorders
Nausea	2/6 (33.3%)	2	0/6 (0%)	0
General disorders
Headache	1/6 (16.7%)	1	3/6 (50%)	3
tooth decay	1/6 (16.7%)	1	1/6 (16.7%)	1
tongue injury	1/6 (16.7%)	1	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Broken Rib	0/6 (0%)	0	1/6 (16.7%)	1
Respiratory, thoracic and mediastinal disorders
Bronchitis	0/6 (0%)	0	2/6 (33.3%)	2

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.