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

Phase 3

Completed

• Conditions: Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy
• Interventions: Drug: Intravitreal bevacizumab; Procedure: Small-gauge pars plana vitrectomy

• Registration Number: NCT01976923
• Lead Sponsor: J. Fernando Arevalo, MD FACS

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.

Study Timeline

• Study First Submitted: 2013-10-25
• Study First Submitted QC: 2013-10-30
• Study Start: 2013-11
• Study First Posted: 2013-11-06
• Primary Completion: 2018-07
• Status Verified: 2018-10
• Study Completion: 2018-10
• Last Update Submitted: 2018-10-07
• Last Update Posted: 2018-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 224

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study arm	Intravitreal bevacizumab	Intravitreal bevacizumab Small-gauge pars plana vitrectomy
Study arm	Small-gauge pars plana vitrectomy	Intravitreal bevacizumab Small-gauge pars plana vitrectomy
Control arm	Small-gauge pars plana vitrectomy	Small-gauge pars plana vitrectomy

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

King Khaled Eye Specialist Hospital; 🇸🇦 Riyadh, Saudi Arabia