Clinical trial NCT02769169: Double-dose Ranibizumab for Polypoidal Choroidal Vasculopathy
Official title: Double-dose Ranibizumab for Polypoidal Choroidal Vasculopathy: A Prospective Randomized Multicenter Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Polypoidal Choroidal Vasculopathy
Keywords: Ranibizumab, regression of the polyps
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2016-05-11
Enrollment: 5
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of participants who have at least 1 polyp resolution
timeFrame: 6 months
Secondary outcomes:
measure: change of best corrected visual acuity(BCVA)
timeFrame: Baseline to 6 months
measure: change of central foveal thickness
timeFrame: Baseline to 6 months
measure: Injection frequency
timeFrame: Baseline to 6 months
measure: Safety analysis: number of adverse event
timeFrame: 6 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhongshan Ophthalmic Center Guangzhou
state: Guangdong
city: Shenzhen
country: China
facility: Retina surgery department, Shenzhen Eye Hospital of Second Clinical Medical College of Jinan University
state: Guangdong
city: Xuzhou
country: China
facility: The First People's Hospital of Xuzhou
state: Jiangsu
city: Shanghai
country: China
facility: Dept. of Ophthalmology，Minhang hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Zhongshan Ophthalmic Center Guangzhou, Guangdong China
name: Lin Lu, MD, phD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Busbee BG, Ho AC, Brown DM, Heier JS, Suner IJ, Li Z, Rubio RG, Lai P; HARBOR Study Group. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2013 May;120(5):1046-56. doi: 10.1016/j.ophtha.2012.10.014. Epub 2013 Jan 23.
citation: Koh A, Lee WK, Chen LJ, Chen SJ, Hashad Y, Kim H, Lai TY, Pilz S, Ruamviboonsuk P, Tokaji E, Weisberger A, Lim TH. EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina. 2012 Sep;32(8):1453-64. doi: 10.1097/IAE.0b013e31824f91e8.
citation: Kokame GT. Prospective evaluation of subretinal vessel location in polypoidal choroidal vasculopathy (PCV) and response of hemorrhagic and exudative PCV to high-dose antiangiogenic therapy (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2014 Jul;112:74-93.
citation: Kokame GT, Yeung L, Lai JC. Continuous anti-VEGF treatment with ranibizumab for polypoidal choroidal vasculopathy: 6-month results. Br J Ophthalmol. 2010 Mar;94(3):297-301. doi: 10.1136/bjo.2008.150029. Epub 2009 Sep 1.
citation: Obata R, Yanagi Y, Kami J, Takahashi H, Inoue Y, Tamaki Y. Polypoidal choroidal vasculopathy and retinochoroidal anastomosis in Japanese patients eligible for photodynamic therapy for exudative age-related macular degeneration. Jpn J Ophthalmol. 2006 Jul-Aug;50(4):354-360. doi: 10.1007/s10384-005-0337-2.
citation: Sho K, Takahashi K, Yamada H, Wada M, Nagai Y, Otsuji T, Nishikawa M, Mitsuma Y, Yamazaki Y, Matsumura M, Uyama M. Polypoidal choroidal vasculopathy: incidence, demographic features, and clinical characteristics. Arch Ophthalmol. 2003 Oct;121(10):1392-6. doi: 10.1001/archopht.121.10.1392.