<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03042871</url>
  </required_header>
  <id_info>
    <org_study_id>2015002</org_study_id>
    <nct_id>NCT03042871</nct_id>
  </id_info>
  <brief_title>Dosing Strategy of Intravitreal Ranibizumab for Pathological Myopia Choroidal Neovascularization</brief_title>
  <acronym>SMILE</acronym>
  <official_title>Dosing Strategy of Intravitreal Ranibizumab for Myopia Choroidal Neovascularization: a Single Center Randomized Prospective Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhongshan Ophthalmic Center, Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhongshan Ophthalmic Center, Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the efficacy (times of injection, change of visual&#xD;
      acuity and Cva/ I) and safety (macular visual function and choroidal thickness) of different&#xD;
      dosing of ranibizumab intravitreal injection (1+PRN vs. 3+PRN) in treating with pathological&#xD;
      myopia choroidal neovascularization (PM-CNV).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PM is a common disease in east asia, while PM-CNV affect 5%-10% PM patients.PM-CNV has&#xD;
      specific characteristics, including small dimensions and limited exudative manifestations&#xD;
      comparing with age-related macular degeneration. However, treatment regimen and re-treatment&#xD;
      criteria follow the PrONTO protocol. The question of the optimal dose and treatment regimen&#xD;
      in myopic CNV management is still unresolved. There is no unequivocal evidence suggesting hat&#xD;
      PRN treatment is more effective than a loading phase followed by an as-needed variable dosage&#xD;
      regimen.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2015</start_date>
  <completion_date type="Actual">July 2018</completion_date>
  <primary_completion_date type="Actual">July 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Injection Number</measure>
    <time_frame>12 months</time_frame>
    <description>Total IRV injection number</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Best corrected visual acuity (BCVA)</measure>
    <time_frame>Change from baseline to 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Retinal sensitivities on microperimetry</measure>
    <time_frame>Baseline and monthly after enrollment from baseline up to 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Electrical response densities in the foveal on multifocal electroretinogram</measure>
    <time_frame>Baseline, 3 months, 6 months and 12 months after enrollment.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alterations of optic coherence tomography angiography</measure>
    <time_frame>Baseline, 3 months, 6 months and 12 months after enrollment.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Retinal thickness on optic coherence tomography</measure>
    <time_frame>Baseline and monthly after enrollment up to 12 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leakage in lesion on fluorescein fundus angiography</measure>
    <time_frame>Baseline, 3 months, 6 months and 12 months after enrollment.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fixation stability on microperimetry</measure>
    <time_frame>Baseline and monthly after enrollment from baseline up to 12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Choroidal Neovascularization</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group A included 30 patients treated with one 0.5mg intravitreal ranibizumab injection. All patients were followed monthly for 12 months with additional injections performed as needed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group B included 30 patients treated with three monthly 0.5mg intravitreal ranibizumab injections. All patients were followed monthly for 12 months with additional injections performed as needed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.5mg intravitreal ranibizumab</intervention_name>
    <description>Patients received ranibizumab (0.5mg, Novartis AG, Basel, Switzerland) via a pars plana transcleral injection through 30-gauge needle at 3.5 to 4mm of inferotemporal limbus. Levofloxacin eye drops ( Cravit Eye Drops, Santen, Japan) was instilled 4 times a day in the study eye before the treatment at least 1 day. Povidone-iodine (5%, Luofushan Pharmaceutical Co., China) was applied to the conjunctiva bulbi and the fornices for at least 3 minutes before injection. Patients were instructed to continue the levofloxacin eye drops 4 times a day for 3 days</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
    <other_name>IVR 0.5mg</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  older then 18 years old&#xD;
&#xD;
          -  refractive error ≥ -6.0 diopters or axial length ≥ 26.0mm&#xD;
&#xD;
          -  active CNV due to high myopic which is the only reason cause visual loss confirmed by&#xD;
             fluorescein fundus angiography&#xD;
&#xD;
          -  BCVA ≥ 24.0 and ≤73 letters at a starting distance of 4 meters using Early Treatment&#xD;
             Diabetic Retinopathy Study visual acuity chart.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  history of (a) stroke,(b) laser photocoagulation involved macular area in study eye,&#xD;
             (c) intraocular treatment with corticosteroids or intraocular surgery or anti vascular&#xD;
             endothelial growth factor or verteporfin photodynamic therapy within 6 months in study&#xD;
             eye, or (d) hypersensitivity to ranibizumab or fluorescein&#xD;
&#xD;
          -  presence of active infectious disease or confirmed intraocular pressure ≥ 21.0 mmHg&#xD;
&#xD;
          -  pregnant or nursing women&#xD;
&#xD;
          -  uncontrolled high blood pressure ≥ 150/90 mmHg or uncontrolled fasting blood glucose ≥&#xD;
             7 mmol/L&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiaoyan Ding, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>ZZhongShan Ophthalmic Center, Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ZhongShan Ophthalmic Center, Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Van Newkirk MR. The Hong Kong vision study: a pilot assessment of visual impairment in adults. Trans Am Ophthalmol Soc. 1997;95:715-49.</citation>
    <PMID>9440191</PMID>
  </reference>
  <reference>
    <citation>Yoshida T, Ohno-Matsui K, Yasuzumi K, Kojima A, Shimada N, Futagami S, Tokoro T, Mochizuki M. Myopic choroidal neovascularization: a 10-year follow-up. Ophthalmology. 2003 Jul;110(7):1297-305. doi: 10.1016/S0161-6420(03)00461-5.</citation>
    <PMID>12867382</PMID>
  </reference>
  <reference>
    <citation>Wong TY, Foster PJ, Hee J, Ng TP, Tielsch JM, Chew SJ, Johnson GJ, Seah SK. Prevalence and risk factors for refractive errors in adult Chinese in Singapore. Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2486-94.</citation>
    <PMID>10937558</PMID>
  </reference>
  <reference>
    <citation>Chan WM, Ohji M, Lai TY, Liu DT, Tano Y, Lam DS. Choroidal neovascularisation in pathological myopia: an update in management. Br J Ophthalmol. 2005 Nov;89(11):1522-8. doi: 10.1136/bjo.2005.074716.</citation>
    <PMID>16234465</PMID>
  </reference>
  <reference>
    <citation>Jones D, Luensmann D. The prevalence and impact of high myopia. Eye Contact Lens. 2012 May;38(3):188-96. doi: 10.1097/ICL.0b013e31824ccbc3.</citation>
    <PMID>22495679</PMID>
  </reference>
  <reference>
    <citation>Miller DG, Singerman LJ. Vision loss in younger patients: a review of choroidal neovascularization. Optom Vis Sci. 2006 May;83(5):316-25. doi: 10.1097/01.opx.0000216019.88256.eb.</citation>
    <PMID>16699445</PMID>
  </reference>
  <reference>
    <citation>Sun J, Zhou J, Zhao P, Lian J, Zhu H, Zhou Y, Sun Y, Wang Y, Zhao L, Wei Y, Wang L, Cun B, Ge S, Fan X. High prevalence of myopia and high myopia in 5060 Chinese university students in Shanghai. Invest Ophthalmol Vis Sci. 2012 Nov 1;53(12):7504-9. doi: 10.1167/iovs.11-8343.</citation>
    <PMID>23060137</PMID>
  </reference>
  <reference>
    <citation>Nagaoka N, Shimada N, Hayashi W, Hayashi K, Moriyama M, Yoshida T, Tokoro T, Ohno-Matsui K. Characteristics of periconus choroidal neovascularization in pathologic myopia. Am J Ophthalmol. 2011 Sep;152(3):420-427.e1. doi: 10.1016/j.ajo.2011.03.002. Epub 2011 Jun 22.</citation>
    <PMID>21696698</PMID>
  </reference>
  <reference>
    <citation>Verteporfin in Photodynamic Therapy Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial--VIP report no. 1. Ophthalmology. 2001 May;108(5):841-52. doi: 10.1016/s0161-6420(01)00544-9.</citation>
    <PMID>11320011</PMID>
  </reference>
  <reference>
    <citation>Blinder KJ, Blumenkranz MS, Bressler NM, Bressler SB, Donato G, Lewis H, Lim JI, Menchini U, Miller JW, Mones JM, Potter MJ, Pournaras C, Reaves A, Rosenfeld P, Schachat AP, Schmidt-Erfurth U, Sickenberg M, Singerman LJ, Slakter JS, Strong HA, Virgili G, Williams GA. Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial--VIP report no. 3. Ophthalmology. 2003 Apr;110(4):667-73. doi: 10.1016/s0161-6420(02)01998-x.</citation>
    <PMID>12689884</PMID>
  </reference>
  <reference>
    <citation>Nguyen QD, Shah S, Tatlipinar S, Do DV, Anden EV, Campochiaro PA. Bevacizumab suppresses choroidal neovascularisation caused by pathological myopia. Br J Ophthalmol. 2005 Oct;89(10):1368-70. No abstract available. Erratum In: Br J Ophthalmol. 2006 Jan;90(1):125.</citation>
    <PMID>16170134</PMID>
  </reference>
  <reference>
    <citation>Wolf S, Balciuniene VJ, Laganovska G, Menchini U, Ohno-Matsui K, Sharma T, Wong TY, Silva R, Pilz S, Gekkieva M; RADIANCE Study Group. RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology. 2014 Mar;121(3):682-92.e2. doi: 10.1016/j.ophtha.2013.10.023. Epub 2013 Dec 8.</citation>
    <PMID>24326106</PMID>
  </reference>
  <reference>
    <citation>Grunwald JE, Daniel E, Huang J, Ying GS, Maguire MG, Toth CA, Jaffe GJ, Fine SL, Blodi B, Klein ML, Martin AA, Hagstrom SA, Martin DF; CATT Research Group. Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2014 Jan;121(1):150-161. doi: 10.1016/j.ophtha.2013.08.015. Epub 2013 Sep 29.</citation>
    <PMID>24084496</PMID>
  </reference>
  <reference>
    <citation>Kung YH, Wu TT, Huang YH. One-year outcome of two different initial dosing regimens of intravitreal ranibizumab for myopic choroidal neovascularization. Acta Ophthalmol. 2014 Dec;92(8):e615-20. doi: 10.1111/aos.12457. Epub 2014 Jun 12.</citation>
    <PMID>24924911</PMID>
  </reference>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 21, 2016</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>March 7, 2019</last_update_submitted>
  <last_update_submitted_qc>March 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Zhongshan Ophthalmic Center, Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Xiaoyan Ding</investigator_full_name>
    <investigator_title>Professor,PhD,MD</investigator_title>
  </responsible_party>
  <keyword>PM-CNV ,Ranibizumab, Dosing Strategy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Choroidal Neovascularization</mesh_term>
    <mesh_term>Neovascularization, Pathologic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ranibizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03042871
org study id: 2015002
nct id: NCT03042871
lead sponsor: 
has dmc: Yes
The purpose of this study is to compare the efficacy (times of injection, change of visual
      acuity and Cva/ I) and safety (macular visual function and choroidal thickness) of different
      dosing of ranibizumab intravitreal injection (1+PRN vs. 3+PRN) in treating with pathological
      myopia choroidal neovascularization (PM-CNV).
PM is a common disease in east asia, while PM-CNV affect 5%-10% PM patients.PM-CNV has
      specific characteristics, including small dimensions and limited exudative manifestations
      comparing with age-related macular degeneration. However, treatment regimen and re-treatment
      criteria follow the PrONTO protocol. The question of the optimal dose and treatment regimen
      in myopic CNV management is still unresolved. There is no unequivocal evidence suggesting hat
      PRN treatment is more effective than a loading phase followed by an as-needed variable dosage
      regimen.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Injection Number
time frame: 12 months
description: Total IRV injection number
measure: Best corrected visual acuity (BCVA)
time frame: Change from baseline to 12 months
measure: Retinal sensitivities on microperimetry
time frame: Baseline and monthly after enrollment from baseline up to 12 months
measure: Electrical response densities in the foveal on multifocal electroretinogram
time frame: Baseline, 3 months, 6 months and 12 months after enrollment.
measure: Alterations of optic coherence tomography angiography
time frame: Baseline, 3 months, 6 months and 12 months after enrollment.
measure: Retinal thickness on optic coherence tomography
time frame: Baseline and monthly after enrollment up to 12 months.
measure: Leakage in lesion on fluorescein fundus angiography
time frame: Baseline, 3 months, 6 months and 12 months after enrollment.
measure: Fixation stability on microperimetry
time frame: Baseline and monthly after enrollment from baseline up to 12 months
arm group label: Group A
arm group type: Active Comparator
description: Group A included 30 patients treated with one 0.5mg intravitreal ranibizumab injection. All patients were followed monthly for 12 months with additional injections performed as needed.
arm group label: Group B
arm group type: Active Comparator
description: Group B included 30 patients treated with three monthly 0.5mg intravitreal ranibizumab injections. All patients were followed monthly for 12 months with additional injections performed as needed.
intervention type: Drug
intervention name: 0.5mg intravitreal ranibizumab
description: Patients received ranibizumab (0.5mg, Novartis AG, Basel, Switzerland) via a pars plana transcleral injection through 30-gauge needle at 3.5 to 4mm of inferotemporal limbus. Levofloxacin eye drops ( Cravit Eye Drops, Santen, Japan) was instilled 4 times a day in the study eye before the treatment at least 1 day. Povidone-iodine (5%, Luofushan Pharmaceutical Co., China) was applied to the conjunctiva bulbi and the fornices for at least 3 minutes before injection. Patients were instructed to continue the levofloxacin eye drops 4 times a day for 3 days
arm group label: Group A
arm group label: Group B
other name: IVR 0.5mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Xiaoyan Ding, PhD
role: Study Chair
affiliation: ZZhongShan Ophthalmic Center, Sun Yat-sen University
facility: 
country: China
citation: Van Newkirk MR. The Hong Kong vision study: a pilot assessment of visual impairment in adults. Trans Am Ophthalmol Soc. 1997;95:715-49.
PMID: 9440191
citation: Yoshida T, Ohno-Matsui K, Yasuzumi K, Kojima A, Shimada N, Futagami S, Tokoro T, Mochizuki M. Myopic choroidal neovascularization: a 10-year follow-up. Ophthalmology. 2003 Jul;110(7):1297-305. doi: 10.1016/S0161-6420(03)00461-5.
PMID: 12867382
citation: Wong TY, Foster PJ, Hee J, Ng TP, Tielsch JM, Chew SJ, Johnson GJ, Seah SK. Prevalence and risk factors for refractive errors in adult Chinese in Singapore. Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2486-94.
PMID: 10937558
citation: Chan WM, Ohji M, Lai TY, Liu DT, Tano Y, Lam DS. Choroidal neovascularisation in pathological myopia: an update in management. Br J Ophthalmol. 2005 Nov;89(11):1522-8. doi: 10.1136/bjo.2005.074716.
PMID: 16234465
citation: Jones D, Luensmann D. The prevalence and impact of high myopia. Eye Contact Lens. 2012 May;38(3):188-96. doi: 10.1097/ICL.0b013e31824ccbc3.
PMID: 22495679
citation: Miller DG, Singerman LJ. Vision loss in younger patients: a review of choroidal neovascularization. Optom Vis Sci. 2006 May;83(5):316-25. doi: 10.1097/01.opx.0000216019.88256.eb.
PMID: 16699445
citation: Sun J, Zhou J, Zhao P, Lian J, Zhu H, Zhou Y, Sun Y, Wang Y, Zhao L, Wei Y, Wang L, Cun B, Ge S, Fan X. High prevalence of myopia and high myopia in 5060 Chinese university students in Shanghai. Invest Ophthalmol Vis Sci. 2012 Nov 1;53(12):7504-9. doi: 10.1167/iovs.11-8343.
PMID: 23060137
citation: Nagaoka N, Shimada N, Hayashi W, Hayashi K, Moriyama M, Yoshida T, Tokoro T, Ohno-Matsui K. Characteristics of periconus choroidal neovascularization in pathologic myopia. Am J Ophthalmol. 2011 Sep;152(3):420-427.e1. doi: 10.1016/j.ajo.2011.03.002. Epub 2011 Jun 22.
PMID: 21696698
citation: Verteporfin in Photodynamic Therapy Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial--VIP report no. 1. Ophthalmology. 2001 May;108(5):841-52. doi: 10.1016/s0161-6420(01)00544-9.
PMID: 11320011
citation: Blinder KJ, Blumenkranz MS, Bressler NM, Bressler SB, Donato G, Lewis H, Lim JI, Menchini U, Miller JW, Mones JM, Potter MJ, Pournaras C, Reaves A, Rosenfeld P, Schachat AP, Schmidt-Erfurth U, Sickenberg M, Singerman LJ, Slakter JS, Strong HA, Virgili G, Williams GA. Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial--VIP report no. 3. Ophthalmology. 2003 Apr;110(4):667-73. doi: 10.1016/s0161-6420(02)01998-x.
PMID: 12689884
citation: Nguyen QD, Shah S, Tatlipinar S, Do DV, Anden EV, Campochiaro PA. Bevacizumab suppresses choroidal neovascularisation caused by pathological myopia. Br J Ophthalmol. 2005 Oct;89(10):1368-70. No abstract available. Erratum In: Br J Ophthalmol. 2006 Jan;90(1):125.
PMID: 16170134
citation: Wolf S, Balciuniene VJ, Laganovska G, Menchini U, Ohno-Matsui K, Sharma T, Wong TY, Silva R, Pilz S, Gekkieva M; RADIANCE Study Group. RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology. 2014 Mar;121(3):682-92.e2. doi: 10.1016/j.ophtha.2013.10.023. Epub 2013 Dec 8.
PMID: 24326106
citation: Grunwald JE, Daniel E, Huang J, Ying GS, Maguire MG, Toth CA, Jaffe GJ, Fine SL, Blodi B, Klein ML, Martin AA, Hagstrom SA, Martin DF; CATT Research Group. Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2014 Jan;121(1):150-161. doi: 10.1016/j.ophtha.2013.08.015. Epub 2013 Sep 29.
PMID: 24084496
citation: Kung YH, Wu TT, Huang YH. One-year outcome of two different initial dosing regimens of intravitreal ranibizumab for myopic choroidal neovascularization. Acta Ophthalmol. 2014 Dec;92(8):e615-20. doi: 10.1111/aos.12457. Epub 2014 Jun 12.
PMID: 24924911
responsible party type: Principal Investigator
investigator affiliation: Zhongshan Ophthalmic Center, Sun Yat-sen University
investigator full name: Xiaoyan Ding
investigator title: Professor,PhD,MD
mesh term: Choroidal Neovascularization
mesh term: Neovascularization, Pathologic
mesh term: Ranibizumab
sharing ipd: Undecided