Clinical trial NCT01976923: Pre-Operative Intravitreal Bevacizumab for Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy
Official title: Pre-Operative Intravitreal Bevacizumab for Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy: Results of the Pan-American Collaborative Retina Study (PACORES) Group
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy
Keywords: Intravitreal Bevacizumab
Tractional Retinal Detachment
Proliferative Diabetic Retinopathy
Small gauge pars plana vitrectomy
Intraoperative bleeding
Post-operative vitreous hemorrhage
Visual acuity
Lead sponsor: King Khaled Eye Specialist Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Pan American Collaborative Retina Study Group
First posted: 2013-11-06
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this is study is to assess the efficacy of pre-operative intravitreal bevacizumab (IVB) (Genentech, South San Francisco CA) in improving visual acuity, reducing operative time, complications, intra-operative and post-operative hemorrhage following small gauge pars plana vitrectomy (PPV) (23-gauge, 25-gauge or 27-gauge ) compared to small gauge PPV (23-gauge, 25-gauge or 27-gauge) alone in eyes with tractional retinal detachment (TRD) secondary to proliferative diabetic retinopathy (PDR). Hypothesis: Preoperative IVB may be beneficial for membrane dissection in diabetic tractional retinal detachment with minimally invasive vitreoretinal surgery (23-gauge transconjunctival sutureless vitrectomy \[TSV\]). In addition, post-operative rebleeding may be decreased.

Detailed description: This will be a prospective, randomized, active-controlled study of 224 eyes of patients with the diagnosis of TRD secondary to PDR. Participants will be screened for eligibility. Eligible patients will be examined at baseline to determine their ocular condition and randomized into 2 arms. Patients will be randomized in a 1:1 ratio to the study arm.

1. Control arm: PPV without pre-operative bevacizumab (Sham injection).
2. Study arm: Pre-operative bevacizumab (3-5 days) before PPV.

In the study arm, an intravitreal bevacizumab injection at a dose of 1.25 µg/0.05 mL will be scheduled 3 to 5 days before minimally invasive vitreoretinal surgery (MIVS).

The purpose of the current study is to determine the effectiveness and safety of an intravitreal injection of 1.25 mg of bevacizumab as a pre-operative adjunct to PPV in eyes with TRD secondary to PDR.

Eligibility criteria: Inclusion Criteria:

1. Age \>= 18 years with proliferative diabetic retinopathy (PDR) and tractional retinal detachment (TRD) threatening or involving the fovea.
2. Diagnosis of diabetes mellitus (type 1 or type 2)
3. At least one eye meets the study eye criteria
4. One eye per patient will be included
5. Able and willing to provide informed consent prior to any study-related procedures
6. Best corrected visual acuity 20/40 or less
7. Willing and able to comply with clinic visits and study-related procedures
8. U.S. patients will be required to have a Health Insurance Portability and Accountability Act (HIPAA) authorization; in other countries, as applicable according to national laws

Exclusion Criteria:

Ocular Exclusion Criteria

The following exclusions apply to the study eye only (i.e., they may be present for the non-study eye):

1. TRD is considered to be due to a cause other than diabetes.
2. An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of TRD (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition, optic atrophy).
3. An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect retinal status or alter visual acuity during the course of the study (e.g., retinal vein occlusion, uveitis or other ocular inflammatory disease, glaucoma, etc.)
4. History of treatment for diabetic macular edema or diabetic retinopathy at any time in the past 4 months with anti-vascular endothelial growth factor (VEGF) drugs.
5. History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months of randomization.
6. History of neodymium-doped yttrium aluminium garnet (YAG) capsulotomy performed within 2 months prior to randomization.
7. Intraocular pressure \>= 25 mmHg.
8. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis
9. An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect retinal status or including hypertension, cardiovascular disease, and glycemic control.

Systemic Exclusion Criteria

A participant is not eligible if any of the following exclusion criteria are present:

1. Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.
2. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including hypertension, cardiovascular disease, and glycemic control).
3. Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry.
4. Known allergy to any component of the study drug.
5. Blood pressure \> 180/110 mmHg (systolic above 180 or diastolic above 110).
6. Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
7. Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
8. Systemic anti-VEGF or VEGF treatment within 4 months prior to randomization.
9. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months.
10. Participant is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the first 12 months of the study.
11. Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry.
12. Known allergy to any component of the study drug.
13. Blood pressure \> 180/110 mmHg (systolic above 180 or diastolic above 110).
14. Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
15. Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
16. Systemic anti-VEGF or VEGF treatment within 4 months prior to randomization.
17. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months.
18. Participant is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the first 12 months of the study.
19. History of blood diseases associated with abnormal coagulation.
20. Anti-coagulant therapy (warfarin or heparin).

Primary outcomes:
measure: Intraoperative bleeding
timeFrame: 12 months
measure: Total surgical time
timeFrame: 12 months
measure: Post-operative vitreous hemorrhage
timeFrame: 12 months
measure: Visual acuity change
timeFrame: 12 months
Secondary outcomes:
measure: Number of endodiathermy applications
timeFrame: 12 months
measure: Intraoperative breaks
timeFrame: 12 months
measure: Change in central macular thickness
timeFrame: 12 months
measure: Proportion of eyes gaining at least 15 letters of BCVA
timeFrame: 12 months
Other outcomes:
measure: Molecules in the vitreous humor and epiretinal membranes
timeFrame: 12 months
Locations:
city: Riyadh
country: Saudi Arabia
facility: King Khaled Eye Specialist Hospital
Study officials:
References:
citation: Arevalo JF, Sanchez JG, Saldarriaga L, Berrocal MH, Fromow-Guerra J, Morales-Canton V, Wu L, Maia M, Saravia MJ, Bareno J; Pan American Collaborative Retina Study Group. Retinal detachment after bevacizumab. Ophthalmology. 2011 Nov;118(11):2304.e3-7. doi: 10.1016/j.ophtha.2011.05.015. No abstract available.
citation: Arevalo JF, Sanchez JG, Lasave AF, Wu L, Maia M, Bonafonte S, Brito M, Alezzandrini AA, Restrepo N, Berrocal MH, Saravia M, Farah ME, Fromow-Guerra J, Morales-Canton V. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture. J Ophthalmol. 2011;2011:584238. doi: 10.1155/2011/584238. Epub 2011 Mar 30.
citation: Arevalo JF, Garcia-Amaris RA. Intravitreal bevacizumab for diabetic retinopathy. Curr Diabetes Rev. 2009 Feb;5(1):39-46. doi: 10.2174/157339909787314121.
citation: Arevalo JF, Maia M, Flynn HW Jr, Saravia M, Avery RL, Wu L, Eid Farah M, Pieramici DJ, Berrocal MH, Sanchez JG. Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy. Br J Ophthalmol. 2008 Feb;92(2):213-6. doi: 10.1136/bjo.2007.127142. Epub 2007 Oct 26.