Ranibizumab vs Dexamethasone Implant in Vitrectomized Eyes With Diabetic Macular Edema

• ClinicalTrials.gov Identifier: NCT04089605
• Recruitment Status: Completed
• First Posted: September 13, 2019
• Last Update Posted: September 13, 2019
• Sponsor: Far Eastern Memorial Hospital
• Information provided by (Responsible Party): Jia-Kang Wang, Far Eastern Memorial Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Diabetic Macular Edema	Drug: dexamethasone implant; Drug: Ranibizumab	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ranibizumab and Dexamethasone Implant in Vitrectomized Eyes With Diabetic Macular Edema
• Actual Study Start Date: June 1, 2017
• Actual Primary Completion Date: November 1, 2018
• Actual Study Completion Date: April 30, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: dexamethasone implant; intravitreal dexamethasone implant injections in vitrectomized patients with DME; Other Name: Dexamethasone implants (Ozurdex®, Allergan Inc., Irvine, CA, USA)
Active Comparator: 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.	Drug: Ranibizumab; intravitreal ranibizumab injections in vitrectomized patients with DME; Other Name: (Lucentis®, Ranibizumab (Novartis Pharma AG, Basel, Switzerland, and Genentech Inc., South San Francisco, CA, USA)

Outcome Measures

Primary Outcome Measures :

1. BCVA at Month 6 [ Time Frame: Month 6 ]
   best-corrected visual acuity (BCVA) at the end of intervention
2. CFT at Month 6 [ Time Frame: Month 6 ]
   central foveal thickness (CFT) at the end of intervention

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Taiwan

Far Eastern Memorial Hospital

New Taipei, Taiwan, 105

Sponsors and Collaborators

Far Eastern Memorial Hospital

Investigators

• Study Chair: Shu-Wen Chang, Ph. D.; Far Eastern Memorial Hospital

More Information

Publications of Results:

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.

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.

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.

• Responsible Party: Jia-Kang Wang, Chief of the Vitreoretinal Section of Ophthalmology Department, Far Eastern Memorial Hospital
• ClinicalTrials.gov Identifier: NCT04089605
• Other Study ID Numbers: 105136-E
• First Posted: September 13, 2019
• Last Update Posted: September 13, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Jia-Kang Wang, Far Eastern Memorial Hospital:

dexamethasone implant; vitrectomized; diabetic macular edema; ranibizumab

Additional relevant MeSH terms:

Macular Edema; Edema; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Dexamethasone; Dexamethasone acetate; Ranibizumab; BB 1101; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors