Double-dose Ranibizumab for Polypoidal Choroidal Vasculopathy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether double-dose Ranibizumab are effective to regress the polyps and benefit to the visual outcome in the polypoidal choroidal vasculopathy (PCV).

Detailed Description
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Recently, it's reported that intravitreal high dose Lucentis®（Ranibizumab） could benefit to both regression of the polyps and the relief of macular edema in PCV patients. Since it was a single arm prospective study with a relatively small sample size, randomized clinical trials were needed to confirm the efficacy of high dose Ranibizumab in PCV treatment. In this study, the investigator will compare the efficacy of double-dose (1mg, 3+prn) Raibizumab with regular dose (0.5mg, 3+prn) for PCV treatment.

Official Title
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Double-dose Ranibizumab for Polypoidal Choroidal Vasculopathy: A Prospective Randomized Multicenter Study

Conditions
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Polypoidal Choroidal Vasculopathy

Intervention / Treatment
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* Drug: Lucentis® (Raibizumab) double-dose
* Drug: Lucentis® (Raibizumab) regular-dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 50 years and ≤80; Active PCV confirmed by ICGA+FFA (Indocyanine green angiography + fundus fluorescein angiography); At least one distinguishable polyp was shown in ICGA; BCVA between 24 to 73 letters with ETDRS chart (Early Treatment of Diabetic Retinopathty Study); The greatest linear dimension of the lesion <5400μm. Exclusion Criteria: Previously received treatment of laser retina photocoagulation, transpupillary thermotherapy, pneumatic displacement of subretinal blood or any investigational treatment; Previous photodynamic therapy or anti-Vegf treatment within 6 months in study eye Previously received treatment of photodynamic treatment within 1 month, or any anti-vascular endothelial growth factor (VEGF) intraocular injection in 3 months in the fellow eye; Combine of current vitreous hemorrhage or extensive subretinal hemorrhage (lesion area >30mm2); A history of angioid streaks, presumed ocular histoplasmosis syndrome or pathologic myopia; Experienced retinal pigmental epithelium (RPE) tear, retinal detachment, macular hole or uncontrolled glaucoma; Undergone intraocular surgery (except uncomplicated cataract extraction with intraocular lens implantation); Cataract extraction with intraocular lens implantation within 60 days; Combine of cataract that could require medical or surgical intervention during 12 months; Combine of diabetes mellitus and have poor glucose control (Haemoglobin A1c (HbA1c) >8%); Combine of hypertension and have poor blood pressure control (blood pressure ≥140/95 mmHg after regular antihypertensive drugs treatment); History of myocardial infarction or cerebral infarction in last 6 months; During gestation period or lactation period; Combine of confirmed systemic autoimmune disease or any uncontrollable clinical conditions (e.g. HIV, malignant tumor, active hepatitis, severe systemic disease, diseases need immediately surgical treatment).

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: double-dose<br>double-dose Lucentis® (Raibizumab), 1mg, 3+prn | Drug: Lucentis® (Raibizumab) double-dose<br>* Give patients 1 injection per month at the beginning 3 months. Give patients additional injection as needed. One injection contains 1mg of Lucentis® (Raibizumab). Intervention 'double-dose: Ranibizumab 1mg, 3 injection plus prn' has not been included in any Arm/Group Descriptions.<br>|
| Active Comparator: regular-dose<br>regular-dose Lucentis® (Raibizumab), 0.5mg, 3+prn | Drug: Lucentis® (Raibizumab) regular-dose<br>* Give patients 1 injection per month at the beginning 3 months. Give patients additional injection as needed. One injection contains 0.5mg of Lucentis® (Raibizumab). regular-dose: Ranibizumab 0.5mg, 3 injection plus prn<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who have at least 1 polyp resolution | Number of participants who have at least 1 polyp resolution, assessed by Indocyanine angiography (ICGA) between baseline and Month 6 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of best corrected visual acuity(BCVA) | Mean change in BCVA, from baseline to the end of 6 month. As assessed by changes of number of letters with the ETDRS (Early Treatment of Diabetic Retinopathy Study) chart | Baseline to 6 months | 
| change of central foveal thickness | Mean change of central foveal thickness, from baseline to the end of 6 month. As assessed by optical coherence tomography scanning | Baseline to 6 months | 
| Injection frequency | Average injection number(from baseline to the end of 6 month), assessed by the number of intravitreal injection from baseline to month 6 | Baseline to 6 months | 
| Safety analysis: number of adverse event | Serious ocular adverse events in the study eye, including reduced VA, retinal hemorrhage, endophthalmitis, corneal edema, iridocyclitis, macular degeneration, retinal artery occlusion, retinal tear, retinal vein occlusion and vitreous floaters. Antiplatelet Trialists' Collaboration (APTC) arterial thromboembolic events (ATEs): including deaths (vascular or unknown cause), nonfatal myocardial infarction and hemorrhagic or ischemic nonfatal cerebrovascular accident. Serious adverse event of special interest, including ATE, bleeding/hemorrhage in central nervous system (CNS) or non-CNS, congestive heart failure, fistulae, gastrointestinal perforation, hypertension, venous thrombotic events and wound healing complications. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ranibizumab, regression of the polyps