Ranibizumab vs Dexamethasone Implant in Vitrectomized Eyes With Diabetic Macular Edema

NCT ID: NCT04089605

Last Updated: 2019-09-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-01

Study Completion Date

2019-04-30

Brief Summary

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Vitrectomy is required for removal of vitreous hemorrhage or retinal traction tissue in some patients with proliferative diabetic retinopathy. Post-vitrectomy macular edema may occur in these diabetic patients. Intravitreal injections of anti-VEGF agents or corticosteroid are required for treating diabetic macular edema (DME) in vitrectomized eyes. Intraocular levels of various cytokines may alter in the diabetic eyes following vitrectomy. Pharmacokinetics may be different between various intraocular agents in vitrectomized eyes. Herein our study will prospectively randomize to compare the clinical behavior between intravitreal ranibizumab (IVR) and intravitreal dexamethasone implant (IDI) in vitrectomized patients with DME. To our knowledge, it is the first study involving such subject.

Detailed Description

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Vitrectomy is required for removal of vitreous hemorrhage or retinal traction tissue in some patients with proliferative diabetic retinopathy. Post-vitrectomy macular edema may occur in these diabetic patients. Intravitreal injections of anti-VEGF agents or corticosteroid are required for treating diabetic macular edema (DME) in vitrectomized eyes. Intraocular levels of various cytokines may alter in the diabetic eyes following vitrectomy. Pharmacokinetics may be different between various intraocular agents in vitrectomized eyes. Herein our study will prospectively randomize to compare the clinical behavior between intravitreal ranibizumab (IVR) and intravitreal dexamethasone implant (IDI) in vitrectomized patients with DME. To our knowledge, it is the first study involving such subject.

Pseudophakic vitrectomized eyes with treatment-naïve center-involved DME will be enrolled with one eye in each patient. They are randomized into one group receiving IDI every 3 to 4 months, and the other group undergoing IVR using 3 monthly plus treat-and-extend injections all with monthly follow-up for 6 months. Switch of intravitreal drugs or deferred macular laser is not allowed. Primary outcome measures include change in central foveal thickness (CFT) in 1 mm by spectral-domain optic coherence tomography, and best corrected visual acuity (BCVA) at Month 6. Primary outcome measures include change in CFT and BCVA at Month 6. Injection number, BCVA, CFT, post-injection complications, and IOP are recorded and compared with Wilcoxon signed rank test within the group and Wilcoxon rank sum test between groups. Fisher's exact test is used for categorical comparison between groups. P value less than 0.05 is considered significant.

Conditions

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Diabetic Macular Edema

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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intravitreal dexamethasone implant

The eyes undergo dexamethasone intravitreal implant 0.7 mg injections at baseline and every 3 or 4 months thereafter. Dexamethasone implants are re-injected in minimal 3-month interval if macular edema persisted or recurred with CFT more than 350 μm or manifestation of apparent submacular fluid and/or intramacular cysts. If DME subside with CFT less than 350 μm without accompanying fluid and cysts, repeated injection is mandatory in maximal 4-month interval.

Group Type EXPERIMENTAL

dexamethasone implant

Intervention Type DRUG

intravitreal dexamethasone implant injections in vitrectomized patients with DME

intravitreal ranibizumab

As for intravitreal ranibizumab 0.5 mg (IVR), we use OCT-guided treat-and-extend protocol for DME treatment after modifying the settings of TREX-DME study.4 The regimen include 3 monthly loading doses then extending the treatment injection interval one month more if CFT less than 350 μm without obvious submacular fluid and intramacular cysts. The injection interval shorten one month if CFT more than 350 μm or presence of obvious fluid and/or cysts. The patients are intentionally injected at most every 3 months even DME not existing.

Group Type ACTIVE_COMPARATOR

Ranibizumab

Intervention Type DRUG

intravitreal ranibizumab injections in vitrectomized patients with DME

Interventions

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dexamethasone implant

intravitreal dexamethasone implant injections in vitrectomized patients with DME

Intervention Type DRUG

Ranibizumab

intravitreal ranibizumab injections in vitrectomized patients with DME

Intervention Type DRUG

Other Intervention Names

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Dexamethasone implants (Ozurdex®, Allergan Inc., Irvine, CA, USA) (Lucentis®, Ranibizumab (Novartis Pharma AG, Basel, Switzerland, and Genentech Inc., South San Francisco, CA, USA)

Eligibility Criteria

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Inclusion Criteria

* Age more than 18 years
* Glycosylated hemoglobin (HbA1c) less than 10.0%
* Best-corrected visual acuity (BCVA) between 20/400 to 20/40
* Central foveal thickness (CFT) more than 300 μm in the 1-mm central macular subfield on spectral domain optical coherence tomography (SD-OCT, CIRRUS™ HD-OCT 5000, Carl Zeiss Meditec Inc., Dublin, CA, USA) using 6 radial line scans through the fovea
* Macular leakage on fundus fluorescein angiography (HRA2, Heidelberg Engineering GmbH, Germany)
* The DME pattern can include submacular fluid, cystoid change, and diffuse macular thickening
* All have proliferative diabetic retinopathy treated by panretinal photocoagulation receiving prior vitrectomy without silicone oil or gas inside the vitreous cavity
* Prior intraocular surgery performed as least 3 months ago

Exclusion Criteria

* Pregnant or nursing women
* The patients with the history of thromboembolic events or major surgery within the previous 3 months
* Presence of anterior chamber intraocular lens or subluxated/dislocated posterior chamber intraocular lens
* Presence of uncontrolled hypertension
* Known coagulation abnormalities or current use of anticoagulative medication other than aspirin
* Prior macular photocoagulation or photodynamic therapy
* Presence of active infectious disease or intraocular inflammation
* Intraocular pressure more than 20 mmHg or glaucoma history
* Presence of iris neovascularization/vitreous hemorrhage.
* The DME pattern with accompanying macular traction by epiretinal membrane or posterior hyaloid
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Far Eastern Memorial Hospital

OTHER

Sponsor Role lead

Responsible Party

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Jia-Kang Wang

Chief of the Vitreoretinal Section of Ophthalmology Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shu-Wen Chang, Ph. D.

Role: STUDY_CHAIR

Far Eastern Memorial Hospital

Locations

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Far Eastern Memorial Hospital

New Taipei City, , Taiwan

Site Status

Countries

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Taiwan

References

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Wang JK, Huang TL, Su PY, Chang PY. An updated review of long-term outcomes from randomized controlled trials in approved pharmaceuticals for diabetic macular edema. Eye Sci. 2015 Dec;30(4):176-83.

Reference Type RESULT
PMID: 27215008 (View on PubMed)

Sonoda S, Sakamoto T, Shirasawa M, Yamashita T, Otsuka H, Terasaki H. Correlation between reflectivity of subretinal fluid in OCT images and concentration of intravitreal VEGF in eyes with diabetic macular edema. Invest Ophthalmol Vis Sci. 2013 Aug 9;54(8):5367-74. doi: 10.1167/iovs.13-12382.

Reference Type RESULT
PMID: 23860753 (View on PubMed)

Muether PS, Droege KM, Fauser S. Vascular endothelial growth factor suppression times in patients with diabetic macular oedema treated with ranibizumab. Br J Ophthalmol. 2014 Feb;98(2):179-81. doi: 10.1136/bjophthalmol-2013-303954. Epub 2013 Nov 13.

Reference Type RESULT
PMID: 24227804 (View on PubMed)

Other Identifiers

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105136-E

Identifier Type: -

Identifier Source: org_study_id

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