Pre-Operative Intravitreal Bevacizumab for Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy

Pre-Operative Intravitreal Bevacizumab for Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy: Results of the Pan-American Collaborative Retina Study (PACORES) Group

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.

Study Overview

• Status: Completed
• Conditions: Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy
• Intervention / Treatment: Drug: Intravitreal bevacizumab; Procedure: Small-gauge pars plana vitrectomy

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.

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 3

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia, 11462
    • King Khaled Eye Specialist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study arm; Intravitreal bevacizumab Small-gauge pars plana vitrectomy	Drug: Intravitreal bevacizumab; A sterile lid speculum is used to separate the lids. A subconjunctival injection of 1% lidocaine is applied to the inferotemporal quadrant. A 5% povidone iodine solution is used to disinfect the entire conjunctival surface. 1.25 mg / 0.05 mL of bevacizumab is injected using a 30-gauge needle inserted through the inferotemporal pars plana 3.5 mm from the limbus.; Procedure: Small-gauge pars plana vitrectomy
Sham Comparator: Control arm; Small-gauge pars plana vitrectomy	Procedure: Small-gauge pars plana vitrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative bleeding		12 months
Total surgical time		12 months
Post-operative vitreous hemorrhage	Early (<1 month) and late (≥ 1 month) post-operative vitreous hemorrhage (VH) (Yes or No)	12 months
Visual acuity change	Mean change in best-corrected visual acuity (BCVA) at 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of endodiathermy applications	12 months
Intraoperative breaks	12 months
Change in central macular thickness	12 months
Proportion of eyes gaining at least 15 letters of BCVA	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecules in the vitreous humor and epiretinal membranes	We would now like to examine molecules in the vitreous humor and epiretinal membranes to gain insight and better assess the efficacy and outcomes of pre-operative intravitreal bevacizumab.	12 months

Collaborators and Investigators

• Sponsor: J. Fernando Arevalo, MD FACS
• Collaborators: Pan American Collaborative Retina Study Group

Publications and helpful links

General Publications

• 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.
• 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.
• Arevalo JF, Garcia-Amaris RA. Intravitreal bevacizumab for diabetic retinopathy. Curr Diabetes Rev. 2009 Feb;5(1):39-46. doi: 10.2174/157339909787314121.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: October 25, 2013
• First Submitted That Met QC Criteria: October 30, 2013
• First Posted (Estimate): November 6, 2013

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: October 7, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Proliferative Diabetic Retinopathy; Visual acuity; Intraoperative bleeding; Tractional Retinal Detachment; Intravitreal Bevacizumab; Small gauge pars plana vitrectomy; Post-operative vitreous hemorrhage
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Neoplasms; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Neoplastic Processes; Retinal Diseases; Diabetic Retinopathy; Neoplasm Metastasis; Retinal Detachment; Dissociative Disorders; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 1338-P