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

Sponsor

J. Fernando Arevalo, MD FACS (Other)

Overall Status

Completed

CT.gov ID

NCT01976923

Collaborator

Pan American Collaborative Retina Study Group (Other)

224

Enrollment

Location

Arms

Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tractional Retinal Detachment Secondary to Proliferative Diabetic Retinopathy	Drug: Intravitreal bevacizumab Procedure: Small-gauge pars plana vitrectomy	Phase 3

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.

Control arm: PPV without pre-operative bevacizumab (Sham injection).
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 Design

Study Type:

Interventional

Actual Enrollment :

224 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Nov 1, 2013

Actual Primary Completion Date :

Jul 1, 2018

Actual Study Completion Date :

Oct 1, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Intraoperative bleeding [12 months]
Total surgical time [12 months]
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

Secondary Outcome Measures

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

Molecules in the vitreous humor and epiretinal membranes [12 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age >= 18 years with proliferative diabetic retinopathy (PDR) and tractional retinal detachment (TRD) threatening or involving the fovea.
Diagnosis of diabetes mellitus (type 1 or type 2)
At least one eye meets the study eye criteria
One eye per patient will be included
Able and willing to provide informed consent prior to any study-related procedures
Best corrected visual acuity 20/40 or less
Willing and able to comply with clinic visits and study-related procedures
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):

TRD is considered to be due to a cause other than diabetes.
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).
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.)
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.
History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months of randomization.
History of neodymium-doped yttrium aluminium garnet (YAG) capsulotomy performed within 2 months prior to randomization.
Intraocular pressure >= 25 mmHg.
Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis
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:

Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.
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).
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.
Known allergy to any component of the study drug.
Blood pressure > 180/110 mmHg (systolic above 180 or diastolic above 110).
Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
Systemic anti-VEGF or VEGF treatment within 4 months prior to randomization.
For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months.
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.
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.
Known allergy to any component of the study drug.
Blood pressure > 180/110 mmHg (systolic above 180 or diastolic above 110).
Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
Systemic anti-VEGF or VEGF treatment within 4 months prior to randomization.
For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months.
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.
History of blood diseases associated with abnormal coagulation.
Anti-coagulant therapy (warfarin or heparin).