Ranibizumab in Diabetic Vitrectomy. A Prospective, Randomised Controlled Trial of Ranibizumab Pre-treatment in Diabetic Vitrectomy - a Pilot Study

Study Overview
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Brief Summary
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This study will evaluate the effect of ranibizumab on patients undergoing vitrectomy surgery for the complications of diabetic retinopathy. Vitrectomy surgery can be difficult and bleeding after the operation can reduce vision for patients. Our hypothesis is that injection into the eye of ranibizumab one week before surgery will make the surgery easier, reduce complications and improve outcome. In this trial, patients will be randomly allocated to receive either ranibizumab injection or a placebo injection of saline. Neither the patient, their surgeon, nor the study investigators will know which they have received so that a fair comparison can be made.

Detailed Description
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The RaDiVit study is a pilot randomised controlled trial to evaluate the effect of ranibizumab as an adjunct to diabetic vitrectomy surgery. Patients with complications of proliferative diabetic retinopathy who require vitrectomy surgery will be recruited to this study. Baseline tests will be performed, including refracted visual acuity, B-scan ultrasound, OCT scanning, colour fundus photography and fundus fluorescein angiography. Patients will be randomised 1:1 to receive either ranibizumab intravitreal injection or saline subconjunctival injection. One week later, surgery will be carried out. The baseline tests will be repeated on the day of surgery to examine for any discernible difference between the two groups one week after treatment. Surgery will be video recorded and detailed assessments of the operative details carried out. A vitreous sample and a paired serum sample will be taken at the time of surgery to compare levels of ranibizumab and related cytokines. Follow up visits will take place at six and twelve weeks. Assessments at that point will include: visual acuity OCT scan colour fundus photography and fundus fluorescein angiography

Official Title
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A Prospective, Randomised Controlled Trial of Ranibizumab Pre-treatment in Diabetic Vitrectomy - a Pilot Study

Conditions
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Diabetic Retinopathy, Retinal Neovascularisation

Intervention / Treatment
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* Drug: Ranibizumab
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of either sex aged 18 years or over Diagnosis of diabetes mellitus (type 1 or type 2). Any one of the following will be considered to be sufficient evidence that diabetes is present: Current regular use of insulin for the treatment of diabetes Current regular use of oral anti-hyperglycaemic agents for the treatment of diabetes Documented diabetes by ADA and/or WHO criteria (see Procedures Manual for Diagnosis of Diabetes) Proliferative diabetic retinopathy with complications of this requiring vitrectomy surgery with anticipated delamination of pre-retinal fibrovascular complexes Ability to return for study visits Ability to give informed consent throughout the duration of the study Exclusion Criteria: Hypersensitivity to the active substance or to any of the excipients. Active or suspected ocular or periocular infections. Vitreous haemorrhage presumed to be caused by vitreous traction on a single, focal point of vitreoretinal attachment Cataract that, in the opinion of the investigators, would be significant enough to impair the view during surgery Active severe intraocular inflammation Previous vitrectomy surgery on study eye Vision in fellow eye 3/60 or worse Uncontrolled glaucoma History of stroke, peripheral vascular disease, angina or myocardial infarction within six months prior to randomisation Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomisation Pregnancy or lactation Male or female unwilling to use contraception

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab<br> | Drug: Ranibizumab<br>* Intravitreal injection of ranibizumab, 0.5mg in 0.05ml<br>* Other names: Lucentis;|
| Placebo Comparator: Saline<br> | Drug: Saline<br>* Subconjunctival injection of 0.05ml saline 0.9% w/v<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best corrected visual acuity |  | 12 weeks post-op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ease of performing vitrectomy surgery | Assessed by surgical scoring systems and counting tool usage | One week post injection | 
| Incidence of post-operative vitreous haemorrhage |  | 6 weeks post-op | 
| Extent of retinal neovascularisation |  | 6 weeks post-op | 
| Extent of tractional retinal detachment | Assessed by serial B-scan ultrasound | 1 week post-injection | 
| Extent of macular perfusion | Assessed by fundus fluorescein angiography | 12 weeks post-op | 
| Vitreous and serum levels of ranibizumab and related cytokines | Samples to be taken on day of surgery | One week post-injection | 
| Incidence of post-operative vitreous haemorrhage |  | 12 weeks post-op | 
| Extent of retinal neovascularisation |  | 12 weeks post-op | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Diabetes Complications, Retinal Diseases, Endothelial Growth Factors, Monoclonal Antibodies, Ranibizumab, Vitrectomy, Vitreoretinal Surgery