Clinical trial NCT02976012: Endolaserless Vitrectomy With Intravitreal IAI for PDR-Related VH
Official title: Endolaserless Vitrectomy With Intravitreal Aflibercept Injection for Proliferative Diabetic Retinopathy-Related Vitreous Hemorrhage (LASER LESS TRIAL)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Proliferative Diabetic Retinopathy
Keywords: Proliferative Diabetic Retinopathy
Aflibercept
Vitreous Hemorrhage
Lead sponsor: Southeast Retina Center, Georgia
Sponsor class: OTHER
First posted: 2016-11-29
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase I/II open label, randomized, interventional clinical trial. Study eyes will receive one preoperative intravitreal aflibercept injection (IAI) \<21 days but \>7 days prior to vitrectomy and one intraoperative IAI at end of surgery followed by randomization in a 1:1 ratio into either 4 mandatory postoperative q4weeks IAI followed by mandatory q8 weeks IAI for 52 weeks follow-up (q8 week Group) or 2 mandatory postoperative q4weeks IAI followed by mandatory q16 weeks IAI for 52 weeks follow-up (q16 week Group).

Detailed description: This is a phase I/II open label, randomized, interventional clinical trial. Study eyes will receive one preoperative intravitreal aflibercept injection (IAI) \<21 days but \>7 days prior to vitrectomy and one intraoperative intravitreal aflibercept at end of surgery followed by randomization in a 1:1 ratio into either 4 mandatory postoperative q4weeks IAI followed by mandatory q8 weeks IAI for 52 weeks follow-up (q8 week Group) or 2 mandatory postoperative q4weeks IAI followed by mandatory q16 weeks IAI for 52 weeks follow-up (q16 week Group).

Follow-up visits occur 1 day and 1-2 weeks, and 4 weeks postoperatively and then every 4 weeks from the first postoperative IAI for 52 weeks. One preoperative visit and every postoperative visit (except day one postoperatively) will include ETDRS Best Corrected Visual Acuity (BCVA), Intraocular Pressure (IOP) measurement, Slit lamp biomicroscopy, Indirect ophthalmoscopy, Heidelberg Spectralis Spectral Domain Optical Coherence Tomography (SD-OCT) (no OCT for preoperative visit) and evaluation for systemic and ocular adverse events. Seven standard field photographs and Optos wide-field fluorescein angiography will be performed at postoperative visits at 4, 16, 28, 40,and 52 weeks. Humphrey visual field (HVF) testing (30-2 and 60-4 test patterns) will be performed at postoperative visits at 4 and 52 weeks. Preoperative B scan echography will be required standard of care(SOC) to assess for macular traction, non-macular traction, retinal detachment and vitreous hemorrhage(VH). Identification of traction macular detachment will exclude the patient from the study.

Eligibility criteria: Inclusion Criteria:

1. Adults age \>18 years with Diabetes Mellitus
2. PDR- related vitreous hemorrhage and not of another cause
3. BCVA Vision LP or better
4. Investigator determination that vitrectomy indicated for PDR-related vitreous hemorrhage
5. Willing and able to comply with clinic visits and study-related procedures
6. Provide HIPPA and signed informed consent prior to any study procedures

Exclusion Criteria:

1. A condition per investigator opinion, would preclude participation in the study (unstable medical status, cardiovascular disease, glycemic control, inability to follow up etc.)
2. Participation in an investigational trial within 30 days of enrollment
3. Known allergy to IAI
4. Systemic anti-VEGF or pro-VEGF treatment within 4 months of enrollment
5. For women of childbearing age, pregnant or lactating or intending to become pregnant within the next 3 years
6. History of PRP or peripheral retinal cryopexy or peripheral retinopexy for any reason in the study eye
7. History of vitrectomy in the study eye
8. History or evidence for rhegmatogenous retinal detachment in the study eye
9. Evidence of traction retinal detachment involving or threatening central macula in the study eye
10. Exam evident of external ocular infection (i.e. conjunctivitis, significant blepharitis, chalazion etc)
11. Intravitreal anti-VEGF injection in the study eye \<4weeks from enrollment.
12. Pregnant or breast-feeding women
13. Sexually active men\* or women of childbearing potential\*\* who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device \[IUD\]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) \*Contraception is not required for men with documented vasectomy. \*\*Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Primary outcomes:
measure: • Ocular and systemic safety evaluation for adverse events at any time point through 52 weeks:
timeFrame: Through 52 weeks from Baseline
Secondary outcomes:
measure: Mean change in BCVA letter score
timeFrame: 52 weeks from Baseline
measure: Mean BCVA letter score
timeFrame: 52 weeks from Baseline
measure: Proportion of eyes with progression of PDR
timeFrame: Through 52 weeks from Baseline
measure: Mean OCT CSF thickness
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eyes with OCT CSF thickness <300um
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eyes with absence of Optos widefield fluorescein angiographic macular leakage
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eyes with absence of active neovascularization
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eyes with absence of active neovascularization
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eyes with unchanged, worsened, or improved fluorescein angiographic macular leakage
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eyes with unchanged, worsened, or improved fluorescein angiographic neovascularization
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eyes with unchanged, worsened, or improved fundus photographic DME appearance
timeFrame: Through 52 weeks from Baseline
measure: Mean cumulative score and change for the combined 30-2 and 60-4 HVF test
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eyes requiring additional IAI other than mandatory injections
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eye with progression of PDR requiring rescue PRP standard of care
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eyes requiring PRP or retinopexy
timeFrame: Through 52 weeks from Baseline
measure: Proportion of eyes requiring additional vitrectomy
timeFrame: Through 52 weeks from Baseline
measure: Proportion of enrolled eyes requiring intraoperative endolaser in a PRP pattern at the time of initial vitrectomy
timeFrame: Through 52 weeks from Baseline
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Southeast Retina Center, PC
state: Georgia
Study officials:
affiliation: Southeast Retina Center, PC
name: Dennis M Marcus, MD
role: PRINCIPAL_INVESTIGATOR
References: