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Prospective clinical trial on the safety and efficacy of anti-VEGF treatment combined with vitrectomy for diabetic macular edema with insufficient effect of anti-VEGF treatment (Eyl/ Vit trial)

Prospective clinical trial of Eylea combined with Vitrectomy for DME (Eyl/ Vit trial)

11

Age, years N (Missing) 11 (0) Mean (SD) 60.4 (9.8) Median (IQR) 58.0 (50.0, 69.0) Range 49.0, 75.0 Female or Male, n (%) Female 3 (27.3) Male 8 (72.7) Height, cm N (Missing) 11 (0) Mean (SD) 165.6 (8.8) Median (IQR) 165.5 (160.6, 175.0) Range 150.0, 180.2 Weight, kg N (Missing) 11 (0) Mean (SD) 67.0 (14.2) Median (IQR) 69.1 (60.6, 76.6) Range 41.7, 91.6 Cerebral infarction, n (%) (-) 11 (100.0) Ischemic heart disease, (+) or (-), n (%) (-) 9 (81.8) (+) 2 (18.2) Other past histories, (+) or (-), n (%) (-) 6 (54.5) (+) 5 (45.5) Glaucoma, (+) or (-), n (%) (-) 11 (100.0) Proliferative diabetic retinopathy, (+) or (-), n (%) (-) 6 (54.5) (+) 5 (45.5) Other complication, (+) or (-), n (%) (+) 11 (100.0) Right eye or Left eye, n (%) Right eye 8 (72.7) Left eye 3 (27.3)

Number of registered cases: 11 Number of cases starting the test: 11 Number of cases completed in the study: 10

No adverse events such as diseases that are directly related to this clinical study have occurred, and it is considered that there is no clear association. There are 2 cases of fever, 1 case of diffuse superficial keratitis, 1 case of intestinal obstruction, 1 case of cough, 1 case of Coronavirus infection, 1 case of elevation of intraocular pressure. They have resolved spontaneously or with treatment.

Primary endpoint Comparison of BCVA(LogMAR) and CRT of the target eye at 24 weeks after vitrectomy with baseline (before vitrectomy) The best corrected visual acuity (BCVA) converted to logMAR of the target eye at 24 weeks after vitrectomy was 0.296 +- 0.057, a significant improvement was observed from the baseline (before vitrectomy) of 0.430 +- 0.046 (p =0.0177, paired t-test). Secondary endpoints Secondary efficacy endpoints (1) Comparison of central retinal thickness (CRT) measured by OCT of the target eye 24 weeks after vitrectomy with baseline (before vitrectomy). After 24 weeks, CRT was 370.0 +- 33.2, which was a significant improvement from the baseline of 494.9 +- 46.0 (p =0.0067, paired t-test). (2) Comparison of BCVA(LogMAR) and CRT of the target eye at 48 weeks after vitrectomy with baseline (before vitrectomy) BCVA(LogMAR) after 48 weeks was 0.314 +- 0.067, which showed no significant improvement from the baseline of 0.430 +- 0.046 (p=0.18, paired t-test), CRT was 376.1 +- 52.2 micrometer, a significant improvement from baseline 494.9 +- 46.0 micrometer (p =0.024, paired t-test). (3) Comparison of the following items in the target eye from 4 weeks to 48 weeks after vitrectomy with the values before vitrectomy, before anti-VEGF treatment, and the best values during anti-VEGF treatment. (i) BCVA(LogMAR) (ii) CRT The above evaluation items were evaluated using one-way repeated measures ANOVA. There was a significant improvement in BCVA from before the vitrectomy to 4 - 48 weeks after vitrectomy (p = 0.046), there was a significant improvement in CRT (p < 0.001). There was a significant improvement in BCVA from before the introduction of anti-VEGF treatment to 4 - 48 weeks after vitrectomy (p = 0.031), there was a significant improvement in CRT (p < 0.001). There were no significant changes in both BCVA (LogMAR) from the best value during anti-VEGF treatment to 4 - 48 weeks after vitrectomy (p=0.22), there was a significant increase in CRT (p < 0.001). (4) The following items for each observation period from 4 weeks to 48 weeks after vitrectomy (i) Re-treatment rate: percentage of cases requiring re-administration of anti-VEGF drugs after vitrectomy The re-treatment rate for each observation period from weeks 4 to 48 is as follows. 10, 50, 50, 50, 50, 50, 50, 50, 50, 50, 50, 50 (%) (ii) Maintenance rate: Percentage of cases that do not require re-administration of anti-VEGF drugs after vitrectomy surgery The re-treatment rate by observation period from 4 to 48 weeks is as follows. 90, 50, 50, 50, 50, 50, 50, 50, 50, 50, 50, 50 (%) (iii) Form of macular edema and visual acuity and central retinal thickness by observation period There were 3 cases in which the form of macular edema was CME type, and the BCVA(LogMAR) of this type was 0.51 +- 0.20 at baseline (before vitrectomy), 0.28 +- 0.21 at 24 weeks, and 0.38 +- 0.28 at 48 weeks. CRT was 493 +- 207 micrometer at baseline, 376 +- 48 micrometer at 24 weeks, and 506 +- 286 micrometer at 48 weeks. There were 7 cases with sponge-like type of macular edema, and the BCVA(LogMAR) of this type was 0.40 +- 0.12 at baseline, 0.30 +- 0.18 after 24 weeks, and 0.28 +- 0.19 after 48 weeks. CRT was 496 +- 132 micrometer at baseline, 368 +- 125 micrometer at 24 weeks, and 320 +- 38 micrometer at 48 weeks. (5) Number of intravitreal injections of anti-VEGF agents performed up to 24 and 48 weeks after vitrectomy Five out of 10 cases required intravitreal anti-VEGF injections by 24 weeks after vitrectomy, and the mean number of injections was 0.7 times (0 to 2 times). Five out of 10 cases required intravitreal anti-VEGF injections by 48 weeks after vitrectomy, and the mean number of injections was 1.1 times (0 to 4 times). Secondary safety endpoints (1) Frequency and rate of adverse events and side effects up to 48 weeks after vitrectomy There were no adverse events considered to be related to vitrectomy. (2) Intraocular pressure from 4 weeks to 48 weeks after vitrectomy Although there were cases in which increased intraocular pressure was observed after STTA, there were no significant changes in intraocular pressure related to vitrectomy.

We prospectively performed surgery on cases refractory to anti-VEGF therapy and evaluated the subsequent clinical progress. Baseline BCVA (LogMAR) was 0.430 +- 0.046, CRT was 494.9 +- 46.0, and after 24 weeks, BCVA (LogMAR) was 0.296 +- 0.057, CRT was 370.0 +- 33.2, both of which were significantly improved (P =0.0177, P =0.0067). After 48 weeks, BCVA (LogMAR) was 0.314 +- 0.067 and CRT was 376.1 +- 52.2, with no significant improvement in BCVA (P =0.18), but significant improvement in CRT (P =0.024).

Dec. 01, 2024

No

no

https://jrct.niph.go.jp/latest-detail/jRCTs031210235

Baba Takayuki

Chiba University Hospital

1-8-1, Inohana, Chuo-ku, Chiba-City, Chiba, Japan

babatakayuki@nifty.com

Tatsumi Tomoaki

Chiba University Hospital

1-8-1, Inohana, Chuo-ku, Chiba-City, Chiba, Japan

+81-43-222-7171

ttatsumi@chiba-u.jp

Complete

Aug. 11, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Japanese male and female of 20 to 80 years
2) DME with central involvement in the study eye
3) Patients with a central retinal thickness (CRT) of 400 micrometer or more after 3 consecutive injections of Eylea, or patients with a CRT increases of 30% or more within 16 weeks even if the CRT decreased to less than 400 micrometers after 3 consecutive injections of Eylea
In cases that both eyes meet inclusion criteria and vitrectomy is performed to both eyes, the subject is only one eye, and in principle, the eye to be operated on first is the subject eye

1) New patient
2) Last-eye patient (one-eye blindness)
3) Poor glycemic control (HbA1c 9.0% or higher)
4) Uncontrolled hypertension (systolic blood pressure> 180 mmHg or diastolic blood pressure> 110 mmHg)
5) Dialysis patients or patients with severe renal dysfunction who are considering the introduction of dialysis
6) Patients with thickened epiretinal membrane or posterior vitreous membrane in the study eye, without retinal edema in their OCT images, with less than 10% improvement in central retinal thickness by 3 consecutive injections of anti-VEGF agents
7) Patients with cataracts that clearly affect visual acuity in the study eye
8) Patients who underwent panretinal photocoagulation within 180 days of vitrectomy in the study eye
9) Patients who received intraocular or periocular steroids within 120 days of vitrectomy in the study eye
10) Patients who underwent cataract surgery or other intraocular surgery within 90 days of vitrectomy in the study eye
11) Patients who have a history of filtration surgery for the treatment of glaucoma in the study eye, or who are expected to need it in the future
12) Patients with a history of idiopathic or autoimmune uveitis in the study eye
13) Patients with iris neovascularization and tractional retinal detachment in the study eye
14) Patients with central macular structural damage such as retinal pigment epithelial atrophy, subretinal fibrosis or scarring, severe macular ischemia or organic hard macula that interferes with visual acuity improvement after macular edema disappears in the study eye
15) Patients with marked fluctuations in symptoms and findings
16) Patients who cannot understand the contents and procedures of this study
17) Patients who are participating in the other research
18) Patients who have difficulty going to the hospital
19) Patients who are judged by the investigator or the investigator to be unsuitable for conducting this study safely

Both

diabetic macular edema

Vitrectomy is performed to the case of diabetic macular edema with inadequate effects of anti-VEGF agents.
Observation is performed every 4 weeks.
Administer anti-VEGF agent if retreatment criteria are met.

diabetes mellitus, diabetic retinopathy, macular edema, anti-VEGF agents

vitrectomy, anti-VEGF treatment

Change in best corrected visual acuity (logMAR) from baseline (before vitrectomy)

Change in central retinal thickness from baseline (before vitrectomy)
Number of anti-VEGF treatment after vitrectomy

+81-43-226-2616

Aug. 04, 2021

none