Clinical trial NCT02816710
Conditions: Proliferative Diabetic Retinopathy Tractional Retinal Detachment
Keywords: Conbercept Proliferative diabetic retinopathy Silicone oil tamponade
Sponsor: Ruijin Hospital
Start date: 2016-07-01; Completion date: 2017-09-01
Enrollment: 112 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To evaluate efficacy of different intravitreal Conbercept injection therapy in the treatment of severe proliferative diabetic retinopathy.

Detailed description:
To assess the clinical effects of preoperative, intraoperative or preoperative combined with intraoperative intravitreal conbercept (IVC) injection in pars plana vitrectomy (PPV) with silicone oil tamponade for severe proliferative diabetic retinopathy (PDR). Methods. These patients were randomly assigned to three groups: Group 1 received an IVC injection 3 to 5 days before surgery; Group 2 received an IVC injection at the end of surgery; and Group 3 received an IVC injection 3 to 5 days before PPV as well as an IVC injection at the end of PPV. Follow-up examinations were performed for at least six months after surgery.

Arms: arm 1: Conbercept injection before vitrectomy arm 2: Conbercept injection at the end of vitrectomy arm 3: First conbercept injection before vitrectomy and second at the end of operation.
Interventions: intervention 1: Conbercept
Intervention descriptions: intervention 1: Conbercept is a humanized soluble fusion protein which has a high binding affinity to the Fc region of human immunoglobulin G1 simultaneously. Prior clinical studies have demonstrated that intravitreal conbercept (IVC) inhibits the process of angiogenesis in vivo and in vitro, and has been recognized as a novel effective treatment strategy for neovascularization, providing an alternative treatment option for ophthalmologists.

Protocol documents:
Prot_000.pdf: 
Different Conbercept Injection 
Methods in Treatment of Severe 
Proliferative Diabetic Retinopathy 
 
 
 
NCT02816710 
2016-06-30 
 
 
 
 
 
 
 
 
 
 


Study Protocol 
 
1. Study objectives: 
To evaluate the clinical efficacy of preoperative, intraoperative or preoperative 
combined with intraoperative intravitreal conbercept (IVC) in vitrectomy with 
silicone oil tamponade for severe PDR patients. 
 
2. Study design:  
This is a prospective, open-labelled, randomized controlled trial to assess the 
clinical efficacy of preoperative, intraoperative or preoperative combined with 
intraoperative IVC injection in pars plana vitrectomy (PPV) with silicone oil 
tamponade for patients with severe proliferative diabetic retinopathy (PDR). The 
study was registered on 25 June 2016 (as NCT02816710). 
 
3. Participants: 
2.1 inclusion criteria:  
1. Subjects of either sex aged ≥ 18 years. 
2. Diagnosis of diabetes mellitus (type 1 or type 2); 
3. Active proliferative diabetic retinopathy was clinically evident; 
4. Study eyes required a vitrectomy and silicone oil tamponade due to vitreous 
hemorrhage with significant fibrous proliferation, tractional retinal detachment in 
the posterior pole or complicated retinal detachment, which can be detected by B-
scan ultrasonography. 
5. Ability to give informed consent. 
2.2 exclusion criteria: 
1. Coexistent ocular disease that may interfere with visual outcome; 
2. Prior vitreoretinal surgery or anti-VEGF pharmacotherapy in either eye; 
3. A macula-involving retinal detachment for >6 months in the study eye;  
4. Iris or angle neovascularization and neovascular glaucoma; 


5. known allergy to any components of conbercept formulation 
6. severe external ocular infection;  
7. pregnancy or current oral contraceptive intake;  
8. usage of anticoagulant or antiplatelet therapy; 
9. preoperative or postoperative poor diabetes control [serum hemoglobin A1c 
(HbA1c) >11.0%]; 
10. uncontrolled systemic diseases, such as hypertension, cardiac diseases or 
presenting abnormal coagulation-associated blood diseases; 
11. <6 months of follow-up post initial surgery. 
4. Randomization:  
Patients were recruited at the department of Ophthalmology, Ruijin Hospital, 
affiliated with Shanghai Jiaotong University School of Medicine, between July 
2016 and September 2017, after approval of the local ethics committee. The use of 
conbercepts were discussed with patients, who all gave their written informed 
consent to undergo the procedure, after having been provided with a detailed 
description of the treatment. Eligible subjects after enrollment were randomized 
into one of the three possible treatment groups. Randomization was performed by 
an automated system at a 1: 1:1 ratio to 1 of 3 treatment arms: Group A received 
IVC (0.5 mg/0.05 mL) 3–5 days before PPV, while Group B received IVC 
(0.5mg/0.05 mL) at the end of PPV. Group C received an IVC injection 3 to 5 days 
before PPV as well as an IVC injection at the end of operation. 
5. Interventions: 
Injections were administered according to the product recommendations and 
different time points under controlled aseptic conditions using sterile gloves, a 
sterile drape and a sterile eyelid speculum. Adequate topical anesthesia together 
with a broad-spectrum microbicide were administered prior to injection. All 
patients underwent 23-gauge transconjunctival suture-less vitrectomy using a 23-
gauge trocar and cannula system. Simultaneously, phacoemulsification and 
aspiration (PEA) were performed in patients with cataracts, and an acrylic foldable 
intraocular lens (IOL) was placed in the capsular bag. During the operation, 


hemostasis was maintained by endodiathermy. After vitrectomy, the vitreous body, 
preretinal fibrovascular tissue and tractional membranes were removed using a 
combination of segmentation and delamination techniques. If subretinal fibrotic 
bands were present, these bands were removed through retinotomy with subretinal 
forceps. The surgical endpoint was relief of traction on the macula and neovascular 
fronds that allowed the entire retinal to flatten, with silicone oil tamponade 
subsequently.  
6. Assessments: 
Included patients were followed at 1 day, 1 week, 1 month, 3 months, and 6 months 
after the operation. At baseline, the measurements included: a complete 
ophthalmological examination, with BCVA evaluated using logMAR visual acuity 
measurement, intraocular pressure (IOP), previous history of PRP, lens status, 
preoperative iris neovascularization, surgical indications. During surgery, the 
extent of vitreoretinal adhesion, degree of intraoperative bleeding, frequency of 
electrocoagulation, surgery duration and combined lens extraction were recorded 
carefully. At each time point during postoperative follow-up, incidence of recurrent 
VH, preretinal blood absorption time, BCVA, IOP, rubeosis, NVG, TRD, 
reoperation rate and systemic adverse events were evaluated respectively. 

SAP_001.pdf: 
Different Conbercept Injection 
Methods in Treatment of Severe 
Proliferative Diabetic Retinopathy 
 
 
 
NCT02816710 
2016-06-30 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan  
The results were analyzed using SPSS statistical software (version 19.0 for 
Windows, SPSS, Inc., Chicago, IL). Visual acuities were converted to 
logMAR before the statistical analysis. The Levene test was employed to 
assess the variance homogeneity of data distributions and the Kolmogorov-
Smirnov test was employed to assure the normality of data distributions. 
The difference between groups were analyzed with chi-square test for 
categorical variables. One-way analysis of variance (ANOVA) was used 
for comparisons of normally distributed data, and Tukey’s HSD test was 
used for comparisons of the differences between groups. For data that was 
not normally distributed, a Kruskal-Wallis test was used for data 
comparisons and a Mann Whitney U test was used for determination of the 
differences among the three groups. However, only the variables which 
were found to be statistically significant among the three groups were 
compared between each two groups. Sensitivities at fixed specificities  
(85% and 95%) were calculated for different parameters.