Intravitreal Bevacizumab for the Treatment of CNV in VKH Disease - A Prospective Study

• ClinicalTrials.gov Identifier: NCT02015351
• Recruitment Status: Unknown
• First Posted: December 19, 2013
• Last Update Posted: December 19, 2013
• Sponsor: University of Sao Paulo
• Collaborator: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Information provided by (Responsible Party): Joyce Hisae Yamamoto, University of Sao Paulo

Tracking Information

• First Submitted Date: December 5, 2013
• First Posted Date: December 19, 2013
• Last Update Posted Date: December 19, 2013
• Study Start Date: September 2012
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 12, 2013)

• Visual Acuity change [ Time Frame: 6 months ]
  Visual Acuity will be measured using Snellen charts with best refraction by the same examiner.
• Change in central foveal thickness [ Time Frame: 6 months ]
  Central foveal thickness will be measured manually using the caliper by the same examiner. Measurements will be proceeded from the Bruch's membrane till the internal limiting membrane and comparison with previous measurement will be done.
• Presence or absence of intra/subretinal fluid in OCT [ Time Frame: 6 months ]
  OCT will be analyzed at 6 and 12 months for the presence of intra or subretinal fluid.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: December 12, 2013)

• Visual Acuity change [ Time Frame: 12 months ]
  Visual Acuity will be measured using Snellen charts with best refraction by the same examiner.
• Change in Central Foveal Thickness [ Time Frame: 12 months ]
  Central foveal thickness will be measured manually using the caliper by the same examiner. Measurements will be proceeded from the Bruch's membrane till the internal limiting membrane and comparison with previous measurement will be done.
• Presence or Absence of Intra/Subretinal fluid in OCT [ Time Frame: 12 months ]
  OCT will be analyzed at 6 and 12 months for the presence of intra or subretinal fluid.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Intravitreal Bevacizumab for the Treatment of CNV in VKH Disease - A Prospective Study
• Official Title: Intravitreal Bevacizumab for the Treatment of Choroidal Neovascularization in Vogt-Koyanagi-Harada Disease - A Prospective Study
• Brief Summary: Efficacy of monthly intravitreal anti-vascular endothelial growth factor (VEGF) associated to systemic immunosuppression in patients with Vogt-Koyanagi-Harada Disease and choroidal neovascularization. Minimum follow-up 12 months. Endpoints: 6 and 12 months of follow-up. Outcome measures: improvement of VA, decrease in central foveal thickness as measured by Optical Coherence Tomography (OCT) and absence of intra/subretinal fluid.
• Detailed Description: Choroidal neovascularization (CNV) in Vogt-Koyanagi-Harada (VKH) disease is associated with poor visual prognosis. Several treatments have been suggested, though there is still no standard therapy. CNV diagnosis will be based on fundus biomicroscopy (presence of serous retinal detachment with or without retinal hemorrhages), fluorescein angiography (FA) (presence of early phase hyperfluorescence with late phase leakage) and OCT findings (hyperreflective lesion related to a CNV complex with serous foveal detachment or intraretinal fluid with increased foveal thickness). Inflammation will be considered active if anterior chamber cells or optic disc leakage in FA is observed. Each patient will undergo a complete clinical exam, including best corrected visual acuity (VA) (Snellen charts). Once active CNV is identified, a loading dose of 3 injections of IV bevacizumab will be proceeded monthly and systemic immunosuppression will be introduced or intensified. After the first 3 injections, the patient will be clinically examined and OCT will be proceeded monthly. The persistence of intra/subretinal fluid in the OCT will indicate one more IV bevacizumab injection. Immunosuppression status evaluation will be done at 3, 6, 9 and 12 months of follow up and intensification will be done if inflammatory signs or persistence of intraretinal fluid is observed. Presence of intra/subretinal fluid and manual measurement of retina central foveal thickness (CFT) will be proceeded in horizontal scan by the same examiner.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Choroidal Neovascularization

Intervention

Drug: bevacizumab

Injection technique: After lid speculum insertion and irrigation of the conjunctiva with 5% povidone-iodine, 0,05ml of bevacizumab will be inserted through the pars plana 3.5mm to 4.0mm posterior to the surgical limbus using a 30 gauge needle. After injection, topical antibiotics will be immediately applied in the injected eye. Immunosuppression: Corticosteroids will be prescribed (1mg/Kg/d) with tapering along 5 months. Immunosuppressive drug of choice is cyclosporine (3-5mg/Kg/d). In case of contraindication to cyclosporine use, azathioprine or mycophenolate mofetil will be prescribed.

Other Name: Bevacizumab (Avastin;Genentech Inc,USA)

Study Arms

Experimental: Anti-VEGF and Immunosuppression

Bevacizumab: Dosage 1.25mg/0.05ml; Frequency monthly injections; Duration at least 3 months.

Immunosuppression: cyclosporine and/or azathioprine

Intervention: Drug: bevacizumab

Publications *

• Perentes Y, Van Tran T, Sickenberg M, Herbort CP. Subretinal neovascular membranes complicating uveitis: frequency, treatments, and visual outcome. Ocul Immunol Inflamm. 2005 Apr-Jun;13(2-3):219-24.
• Rouvas A, Petrou P, Douvali M, Ntouraki A, Vergados I, Georgalas I, Markomichelakis N. Intravitreal ranibizumab for the treatment of inflammatory choroidal neovascularization. Retina. 2011 May;31(5):871-9. doi: 10.1097/IAE.0b013e3182003ca8.
• Adán A, Mateo C, Navarro R, Bitrian E, Casaroli-Marano RP. Intravitreal bevacizumab (avastin) injection as primary treatment of inflammatory choroidal neovascularization. Retina. 2007 Nov-Dec;27(9):1180-6.
• Wu L, Evans T, Saravia M, Schlaen A, Couto C. Intravitreal bevacizumab for choroidal neovascularization secondary to Vogt-Koyanagi-Harada syndrome. Jpn J Ophthalmol. 2009 Jan;53(1):57-60. doi: 10.1007/s10384-008-0600-4. Epub 2009 Jan 30.
• Kolomeyer AM, Roy MS, Chu DS. The use of intravitreal ranibizumab for choroidal neovascularization associated with vogt-koyanagi-harada syndrome. Case Rep Med. 2011;2011:747648. doi: 10.1155/2011/747648. Epub 2011 Aug 3.
• Tran TH, Fardeau C, Terrada C, Ducos De Lahitte G, Bodaghi B, Lehoang P. Intravitreal bevacizumab for refractory choroidal neovascularization (CNV) secondary to uveitis. Graefes Arch Clin Exp Ophthalmol. 2008 Dec;246(12):1685-92. doi: 10.1007/s00417-008-0906-4. Epub 2008 Aug 6.
• Nowilaty SR, Bouhaimed M; Photodynamic Therapy Study Group. Photodynamic therapy for subfoveal choroidal neovascularisation in Vogt-Koyanagi-Harada disease. Br J Ophthalmol. 2006 Aug;90(8):982-6. Epub 2006 May 10.
• Mansour AM, Arevalo JF, Ziemssen F, Mehio-Sibai A, Mackensen F, Adan A, Chan WM, Ness T, Banker AS, Dodwell D, Chau Tran TH, Fardeau C, Lehoang P, Mahendradas P, Berrocal M, Tabbarah Z, Hrisomalos N, Hrisomalos F, Al-Salem K, Guthoff R. Long-term visual outcomes of intravitreal bevacizumab in inflammatory ocular neovascularization. Am J Ophthalmol. 2009 Aug;148(2):310-316.e2. doi: 10.1016/j.ajo.2009.03.023. Epub 2009 May 9.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: December 12, 2013): 9
• Original Actual Enrollment: Same as current
• Estimated Study Completion Date: June 2014
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients diagnosed with Vogt-Koyanagi-Harada disease based on Revised Diagnostic Criteria presented by the International Committee on VKH disease in 2001;
2. Presence of choroidal neovascularization identified by fundus biomicroscopy, fluorescein angiography and OCT.

Exclusion Criteria:

• Media opacities precluding posterior segment exam, ametropia over 5 dioptries, glaucoma (defined as a disease with characteristic damage at the optic nerve or characteristic visual field defect with compatible nerve fiber layer lesion), Age related Macular degeneration, impossibility to increase immunosuppression.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 70 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT02015351
• Other Study ID Numbers: Brazilian VKH Study Group
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Joyce Hisae Yamamoto, University of Sao Paulo
• Study Sponsor: University of Sao Paulo
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo

Investigators

• Principal Investigator: Joyce H Yamamoto, MD; University of Sao Paulo School of Medicine Ophthalmology
• Principal Investigator: Viviane M Sakata, MD; University of Sao Paulo

• PRS Account: University of Sao Paulo
• Verification Date: December 2013