Efficacy and Safety Comparison of IVR and IVC Before Vitrectomy in Proliferative Diabetic Retinopathy

• ClinicalTrials.gov Identifier: NCT05414149
• Recruitment Status: Completed
• First Posted: June 10, 2022
• Last Update Posted: June 10, 2022
• Sponsor: Peking University People's Hospital
• Information provided by (Responsible Party): Peking University People's Hospital

Study Description

Brief Summary:

Proliferative diabetic retinopathy (PDR) is the most common causes of irreversible blindness in diabetic retinopathy (DR).Although pars plana vitrectomy (PPV) is the cornerstone for treatment of advanced PDR, related postoperative complications such as recurrent VH, NVG, and postoperative fibrovascular proliferation progression may still cause serious visual impairment. Preoperative intravitreal injections of anti-VEGF drugs may represent a new strategy for making vitrectomy safer and more effective for severe PDR.

Condition or disease	Intervention/treatment	Phase
Proliferative Diabetic Retinopathy	Procedure: preoperative intravitreal injections of ranibizumab or conbercept	Not Applicable

Detailed Description:

Proliferative diabetic retinopathy (PDR) is the most common causes of irreversible blindness in diabetic retinopathy (DR).It is characterized by progressive loss of vision, retinal edema, vitreous hemorrhage (VH), retinal neovascularization, fibrovascular proliferation, tractional retinal detachment (TRD) and neovascular glaucoma (NVG).Although pars plana vitrectomy (PPV) is the cornerstone for treatment of advanced PDR, related postoperative complications such as recurrent VH, NVG, and postoperative fibrovascular proliferation progression may still cause serious visual impairment. It is well known that vascular endothelial growth factor (VEGF) is a leading role of the neovascularization, vascular permeability, and diabetic macular edema.preoperative intravitreal injections of anti-VEGF drugs may represent a new strategy for making vitrectomy safer and more effective for severe PDR.Until now, there are two kinds of anti-VEGF drugs in China, including monoclonal antibodies, like imported drug Ranibizumab, militating by block VEGF-A, and fusion proteins, like domectic drug Conbercept, competitively inhibiting the binding of VEGF with its receptor by blocking multiple targets, VEGF-A, VEGF-B, and placental insulin-like growth factor (PlGF). Studies focusing on the comparison of efficacy between preoperative intravitreal injections of the two drugs for patients with severe PDR undergoing vitrectomy is still limited. Thus, in this study, we aim to carry out a more comprehensive comparison in intraoperative and postoperative aspects on the efficacy and safety between intravitreal ranibizumab injection (IVR) and intravitreal conbercept injection (IVC) before vitrectomy of PDR.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety Comparison of Ranibizumab and Conbercept Pretreatment Before Vitrectomy in Proliferative Diabetic Retinopathy
• Actual Study Start Date: September 1, 2021
• Actual Primary Completion Date: May 31, 2022
• Actual Study Completion Date: May 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: IVR group; Patients that received intravitreal ranibizumab injections (IVR) (0.5mg/0.05ml) before vitreous surgery were assigned to IVR group 3-5 days before three-port transconjunctival 25-G pars plana vitrectomy (PPV). All patients underwent 25-gauge transconjunctival sutureless vitrectomy using the 25-gauge Constellation system (Alcon, Fort Worth, TX, USA) system under local or anesthesia. A speed of 5000 cuts per minute was used for vitrectomy.	Procedure: preoperative intravitreal injections of ranibizumab or conbercept; IVR group means patients received intravitreal ranibizumab injections (IVR) (0.5mg/0.05ml) before vitreous surgery. IVC group means patients that received intravitreal conbercept injection (IVC) (0.5mg/0.05ml) before vitreous surgery.
Experimental: IVC group; Patients that received intravitreal conbercept injection (IVC) (0.5mg/0.05ml) before vitreous surgery were assigned to IVC group 3-5 days before three-port transconjunctival 25-G pars plana vitrectomy (PPV). All patients underwent 25-gauge transconjunctival sutureless vitrectomy using the 25-gauge Constellation system (Alcon, Fort Worth, TX, USA) system under local or anesthesia. A speed of 5000 cuts per minute was used for vitrectomy.	Procedure: preoperative intravitreal injections of ranibizumab or conbercept; IVR group means patients received intravitreal ranibizumab injections (IVR) (0.5mg/0.05ml) before vitreous surgery. IVC group means patients that received intravitreal conbercept injection (IVC) (0.5mg/0.05ml) before vitreous surgery.

Outcome Measures

Primary Outcome Measures :

1. BCVA [ Time Frame: from preoperation to 3 months follow-up ]
   best-corrected visual acuity
2. CRT [ Time Frame: from preoperation to 3 months follow-up ]
   central retinal thickness

Secondary Outcome Measures :

1. surgery time [ Time Frame: during surgery ]
   surgery time
2. intraoperative bleeding [ Time Frame: during surgery ]
   intraoperative bleeding
3. intraocular electrocoagulation use [ Time Frame: during surgery ]
   intraocular electrocoagulation use
4. incidence of iatrogenic retinal breaks [ Time Frame: during surgery ]
   incidence of iatrogenic retinal breaks
5. relaxing retinotomy [ Time Frame: during surgery ]
   relaxing retinotomy
6. retinal reattachment [ Time Frame: during surgery ]
   retinal reattachment
7. silicone oil tamponade [ Time Frame: during surgery ]
   silicone oil tamponade
8. postoperative vitreous hemorrhage (VH) [ Time Frame: during 3 months follow-up ]
   postoperative vitreous hemorrhage (VH)
9. neovascular glaucoma (NVG) [ Time Frame: during 3 months follow-up ]
   neovascular glaucoma (NVG)
10. recurrent retinal detachment [ Time Frame: during 3 months follow-up ]
    recurrent retinal detachment
11. postoperative fibrovascular proliferation progression [ Time Frame: during 3 months follow-up ]
    postoperative fibrovascular proliferation progression

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:

• patients aged 18 years or more with type 1 or 2 diabetes who were clinically diagnosed with diabetic retinopathy (DR); hemoglobin A1c (HbA1c) ≤ 12%;
• persistent VH for more than 1 month or recurrent vitreous hemorrhage (VH) with or without panretinal photocoagulation (PRP);
• TRD detected by indirect ophthalmoscope or B-scan ultrasonography.

Exclusion Criteria:

• previous vitreoretinal surgeries (including vitrectomy, intravitreal drug injection) in the study eyes;
• eyes with any ocular disease that may hinder visual improvement other than PDR, such as optic atrophy or macular hole;
• history of thromboembolic events (including cerebral vascular infarctions or myocardial infarctions) or coagulation system disorders or receiving anticoagulant or antiplatelet therapy;
• eyes given gas tamponade or additional treatment like ranibizumab injection again or supplementary retinal photocoagulation during follow-up periods.

Contacts and Locations

Locations

China, Beijing

Peking University People's Hospital

Beijing, Beijing, China, 100044

Sponsors and Collaborators

Peking University People's Hospital

Investigators

• Study Chair: Jinfeng Qu, MD; Peking University People's Hospital

More Information

Publications:

Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, He J; China National Diabetes and Metabolic Disorders Study Group. Prevalence of diabetes among men and women in China. N Engl J Med. 2010 Mar 25;362(12):1090-101. doi: 10.1056/NEJMoa0908292.

Tseng VL, Greenberg PB, Scott IU, Anderson KL. Compliance with the American Academy of Ophthalmology Preferred Practice Pattern for Diabetic Retinopathy in a resident ophthalmology clinic. Retina. 2010 May;30(5):787-94. doi: 10.1097/IAE.0b013e3181cd47a2.

Bressler SB, Qin H, Melia M, Bressler NM, Beck RW, Chan CK, Grover S, Miller DG; Diabetic Retinopathy Clinical Research Network. Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial. JAMA Ophthalmol. 2013 Aug;131(8):1033-40. doi: 10.1001/jamaophthalmol.2013.4154.

Ehrlich R, Harris A, Ciulla TA, Kheradiya N, Winston DM, Wirostko B. Diabetic macular oedema: physical, physiological and molecular factors contribute to this pathological process. Acta Ophthalmol. 2010 May;88(3):279-91. doi: 10.1111/j.1755-3768.2008.01501.x. Epub 2010 Mar 11. Review.

Wang X, Wang G, Wang Y. Intravitreous vascular endothelial growth factor and hypoxia-inducible factor 1a in patients with proliferative diabetic retinopathy. Am J Ophthalmol. 2009 Dec;148(6):883-9. doi: 10.1016/j.ajo.2009.07.007. Epub 2009 Oct 17.

Yang X, Xu J, Wang R, Mei Y, Lei H, Liu J, Zhang T, Zhao H. A Randomized Controlled Trial of Conbercept Pretreatment before Vitrectomy in Proliferative Diabetic Retinopathy. J Ophthalmol. 2016;2016:2473234. doi: 10.1155/2016/2473234. Epub 2016 Mar 13.

Cui J, Chen H, Lu H, Dong F, Wei D, Jiao Y, Charles S, Gu W, Wang L. Efficacy and Safety of Intravitreal Conbercept, Ranibizumab, and Triamcinolone on 23-Gauge Vitrectomy for Patients with Proliferative Diabetic Retinopathy. J Ophthalmol. 2018 Jun 25;2018:4927259. doi: 10.1155/2018/4927259. eCollection 2018.

• Responsible Party: Peking University People's Hospital
• ClinicalTrials.gov Identifier: NCT05414149
• Other Study ID Numbers: PKUPHophthalmol
• First Posted: June 10, 2022
• Last Update Posted: June 10, 2022
• Last Verified: June 2022

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

Keywords provided by Peking University People's Hospital:

Proliferative diabetic retinopathy; ranibizumab; conbercept

Additional relevant MeSH terms:

Retinal Diseases; Diabetic Retinopathy; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Ranibizumab; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents