Ranibizumab Treatment for Macular Edema Secondary to Retinal Vein Occlusion

Different Regimens of Ranibizumab Treatment for Macular Edema Secondary to Retinal Vein Occlusion: a Randomized and Controlled Clinical Study.

Retinal vein occlusion (RVO) may lead to series of complications including retinal ischemia, macular edema (ME) and induce vision impairment. Intravitreal injection of Ranibizumab (0.5mg) has been proved to be a safe and effective method for the treatment of RVO-ME. In this study, different treatment regimens of Ranibizumab is applied and the effects is observed at 1-6 months to explore the best regimen for RVO. After 6 months, anti-VEGF therapy and/or laser photocoagulation is used to explore whether laser photocoagulation can maintain the therapeutic effect of Ranibizumab or reduce the injection number.

Study Overview

• Status: Unknown
• Conditions: Retinal Vein Occlusion; Treatment; Ranibizumab; Photocoagulation Burn to Retina
• Intervention / Treatment: Drug: Ranibizumab; Device: laser photocoagulation

Detailed Description

Retinal vein occlusion (RVO) may lead to series of complications including retinal ischemia, macular edema (ME) and so on. Retinal vein occlusion (RVO) can be classified as branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). Retinal vein occlusion with macular edema (RVO-ME) is the main cause of RVO induced vision impairment. Intravitreal injection of Ranibizumab (0.5mg) has been proved to be a safe and effective method for the treatment of RVO-ME. Although multiple injections of anti-vascular endothelial growth factor (anti-VEGF) drugs are beneficial to the therapeutic results of RVO-ME, they may also increase the risk of systemic or ocular complications and at the same time increase the economic burden of patients to a certain extent. Different studies have shown that anti-VEGF therapy with low frequency injection (2-5 doses) is also effective for RVO-related ME. However, there are still different views on which option is better. Meanwhile, the effect of laser photocoagulation in the non-perfusion area of the retina, and whether the number of subsequent anti-VEGF injections can be reduced accordingly, is still uncertain. Therefore, in this study, different treatment regimens will be applied and the effects will be observed at 1-6 months. After 6 months, anti-VEGF therapy and/or laser photocoagulation will be used to explore whether laser photocoagulation can maintain the therapeutic effect or reduce the injection number of Ranibizumab. This study intends to explore the therapeutic effects of different treatment regimens on RVO-ME, and meanwhile to investigate the dynamic changes in retinal morphology, microcirculation and visual function during RVO treatment by means of angiography-optical coherence tomography (angio-OCT), microperimetry, electroretinogram (ERG) examination and other methods.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Chuangxin Huang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with RVO-ME diagnosed definitely by FFA and OCT, with CMT > 300μm; BCVA from 20/200 to 20/40 (including 20/200 and 20/40), with a degree of myopia ≤-6 diopter (diopter, D);
2. Patients with a course of RVO ≤ 12 weeks; Patients who have not received laser, intraocular or systemic anti-VEGF treatments or long-acting hormone intraocular, periocular or systemic treatments since the onset of RVO;
3. Patients who are voluntary to sign and date the informed consent form approved by the Ethics Review Committee prior to the conduct of the relevant study steps.

Exclusion Criteria:

1. Patients with a course of disease > 12 weeks;
2. Patients treated with any anti-angiogenic medicines for either eye within 3 months before the baseline; or patients currently in treatment with systemic anti-angiogenic drugs;
3. Patients with their study eyes treated with panretinal photocoagulation (PRP) previously;
4. Patients previously participating in other clinical trials 3 months before the baseline;
5. Patients with severely opacity of refractive media affecting laser treatment and observation;
6. Patients with other ophthalmic diseases affecting visual prognosis, such as corneal disease, glaucoma, severe cataract, uveitis, other fundus diseases, etc.
7. Patients with in any condition where intravitreal injection is unacceptable;
8. Patients identified by the investigator to be medically or mentally unstable: complicated with cardiovascular, cerebrovascular, liver, kidney and hematopoietic system and other serious primary diseases or mental disease; Women who are pregnant or preparing for pregnancy or in lactation, etc.
9. Patients with any history may interfere with the results of the trial or increase the risk of the patient (assessed by the investigator) ;
10. Patients who are in poor compliance and unable to strictly implement the protocol (assessed by the investigator).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1+PRN; Intravitreal injection of Ranibizumab 0.5 mg (IVR): initial injection for 1 time ( month 1), and then IVR is required if central macular thickness (CMT) greater than 300 μm during the follow-up observation (Pro re nata, PRN, means if necessary). After 6 months follow-up, patients in this arm will be randomly divided to receive IVR PRN only or laser photocoagulation combined with IVR PRN. IVR PRN only: patient will receive IVR PRN if CMT greater than 300 μm during the follow-up observation (PRN) after month 6. Laser photocoagulation with IVR PRN: patient will receive laser photocoagulation for non-perfusion area according to FFA results after month 6, and then received IVR PRN if CMT greater than 300 μm.	Drug: Ranibizumab; Patients will receive intravitreal injection of Ranibizumab 0.5 mg (1+PRN or 3+PRN) according to the study until month 6. Then, patients will received Ranibizumab PRN only or laser photocoagulation with Ranibizumab PRN after month 6.; Other Names: Lucentis; Device: laser photocoagulation; After month 6, patients will received Ranibizumab PRN only or laser photocoagulation with Ranibizumab PRN according the re-randomization at month 6.
Active Comparator: 3+PRN; Intravitreal injection of Ranibizumab 0.5 mg (IVR): initial injection for 3 consecutive times ( months 1, 2 and 3 ),and then IVR is required if CMT greater than 300 μm during the follow-up observation (PRN). After 6 months follow-up, patients in this arm will be randomly divided to receive IVR PRN only or laser photocoagulation combined with IVR PRN. IVR PRN only: patient will receive IVR PRN if CMT greater than 300 μm during the follow-up observation (PRN) after month 6. Laser photocoagulation with IVR PRN: patient will receive laser photocoagulation for non-perfusion area according to FFA results after month 6, and then received IVR PRN if CMT greater than 300 μm.	Drug: Ranibizumab; Patients will receive intravitreal injection of Ranibizumab 0.5 mg (1+PRN or 3+PRN) according to the study until month 6. Then, patients will received Ranibizumab PRN only or laser photocoagulation with Ranibizumab PRN after month 6.; Other Names: Lucentis; Device: laser photocoagulation; After month 6, patients will received Ranibizumab PRN only or laser photocoagulation with Ranibizumab PRN according the re-randomization at month 6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
best-corrected visual acuity (BCVA) at month 6	best-corrected visual acuity (BCVA) at month 6	Month 6 after first treatment
Central macular thickness (CMT) at month 6 (3) the number of intravitreal injections of Ranibizumab at month 6	Central macular thickness (CMT) at month 6	Month 6 after first treatment
the number of intravitreal injections of Ranibizumab at month 6	the number of intravitreal injections of Ranibizumab at month 6	Month 6 after first treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
best-corrected visual acuity (BCVA) at month 12	best-corrected visual acuity (BCVA) at month 12	Month 12 after first treatment
the number of intravitreal injections of Ranibizumab at month 12	the number of intravitreal injections of Ranibizumab at month 12	Month 12 after first treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
best-corrected visual acuity (BCVA) during the follow-up	best-corrected visual acuity (BCVA) during the follow-up	during the follow-up for up to 12 months.
intraocular pressure during the follow-up	intraocular pressure during the follow-up	during the follow-up for up to 12 months.
central macular thickness during the follow-up	central macular thickness during the follow-up	during the follow-up for up to 12 months.
posterior choroidal thickness during the follow-up	posterior choroidal thickness during the follow-up	during the follow-up for up to 12 months.
The results of angio-optical coherence tomography (angio-OCT) examination during the follow-up	The results of angio-OCT examination, including area of non-perfusion and neovascularization.	during the follow-up for up to 12 months.
Fundus fluorescein angiography (FFA) examination results during the follow-up	FFA examination results during the follow-up, including area of non-perfusion and neovascularization.	during the follow-up for up to 12 months.
Microperimetry during the follow-up	Changes in posterior pole found by microperimetry	during the follow-up for up to 12 months.
Electroretinogram (ERG) during the follow-up	Amplitudes and implicit times of the a wave and b wave of ERG during the follow-up	during the follow-up for up to 12 months.
adverse events occurring in the follow-up	Records of adverse events occurring in the follow-up period: including subconjunctival hemorrhage, infection, increased intraocular pressure, retinal tear, retinal detachment, etc.	during the follow-up for up to 12 months.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Chenjin Jin, Ph.D, Zhongshan Ophthalmic Center, Sun Yat-sen University

Publications and helpful links

General Publications

• Campochiaro PA, Hafiz G, Mir TA, Scott AW, Solomon S, Zimmer-Galler I, Sodhi A, Duh E, Ying H, Wenick A, Shah SM, Do DV, Nguyen QD, Kherani S, Sophie R. Scatter Photocoagulation Does Not Reduce Macular Edema or Treatment Burden in Patients with Retinal Vein Occlusion: The RELATE Trial. Ophthalmology. 2015 Jul;122(7):1426-37. doi: 10.1016/j.ophtha.2015.04.006. Epub 2015 May 9.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): August 31, 2022
• Study Completion (Anticipated): August 31, 2022

Study Registration Dates

• First Submitted: July 29, 2019
• First Submitted That Met QC Criteria: August 18, 2019
• First Posted (Actual): August 20, 2019

Study Record Updates

• Last Update Posted (Actual): August 20, 2019
• Last Update Submitted That Met QC Criteria: August 18, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: 2019KYPJ092

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No