<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/NCT03244982</url>
  </required_header>
  <id_info>
    <org_study_id>23897543</org_study_id>
    <nct_id>NCT03244982</nct_id>
  </id_info>
  <brief_title>Fluorescein Angiography With a Full-dose Versus a Half-dose of Intravenous Fluorescein</brief_title>
  <official_title>Comparison of Timing and Image Quality of Different Phases of Optos Fluorescein Angiography Between Two Doses of Intravenous Fluorescein: 250mg Versus 500mg</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kresge Eye Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kresge Eye Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fluorescein angiography is a common procedure used in ophthalmology to diagnose and monitor&#xD;
      diseases of the eye. The standard dose of fluorescein dye used in fluorescein angiography is&#xD;
      500mg. It is common practice to give patients who have previously had an adverse reaction to&#xD;
      fluorescein dye a half-dose, or 250mg, of fluorescein. It has been determined by our&#xD;
      institution that anecdotally, there is no difference in image quality between the images&#xD;
      created by a half-dose of fluorescein versus a full dose of fluorescein. Therefore, this&#xD;
      study seeks to determine whether these doses are actually equivalent in terms of image&#xD;
      quality. Patients who consent to participate in the study will be randomized to receive&#xD;
      either a half or a full dose of intravenous fluorescein, and their images will be compared&#xD;
      subjectively using a masked team of retinal surgeons and residents. We hypothesize that there&#xD;
      will be no significant difference between the images obtained using a half-dose versus a full&#xD;
      dose of intravenous fluorescein.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Fluorescein angiography is a common procedure used in ophthalmology to diagnose and monitor&#xD;
      diseases of the retinal and choroidal blood vessels. The most commonly seen adverse reactions&#xD;
      to fluorescein angiography include nausea, vomiting, and urticaria. More severe reactions&#xD;
      such as anaphylaxis are rare, occurring in only 1 of 2247 patients (0.4%) in a recent&#xD;
      retrospective study. The standard dose of intravenous fluorescein used for fluorescein&#xD;
      angiography is 500mg given intravenously in a 10% or 25% solution. One study from 2008&#xD;
      attempted to compare a 200mg dose versus a 500mg dose of intravenous fluorescein, and found&#xD;
      that 200mg produced inferior image quality. However, the quality of the cameras used for&#xD;
      fluorescein angiography has improved significantly in the last 10 years, and the scanning&#xD;
      laser ophthalmoscope currently used for fluorescein angiography in our clinic (Optos) is&#xD;
      significantly more effective than the fundus camera used in the 2008 study (Topcon). The&#xD;
      scanning laser ophthalmoscope uses a fundamentally different imaging technique than the&#xD;
      traditional fundus camera, with a much narrower illumination source, and has been shown to be&#xD;
      significantly more sensitive in the detection of retinal vascular leakage.&#xD;
&#xD;
      A commonly used method for preventing adverse reactions in patients who have previously had&#xD;
      an adverse reaction to intravenous fluorescein is to use a 250mg dose instead of the standard&#xD;
      500mg dose, despite the lack of evidence to this effect. In our anecdotal experience, a 250mg&#xD;
      dose of intravenous fluorescein, used in patients whom have previously experienced an adverse&#xD;
      reaction, has produced images of equivalent quality to the images produced using a full 500mg&#xD;
      dose. To our knowledge, no study has compared a 500mg dose of intravenous fluorescein with a&#xD;
      lower dose since the 2008 study previously mentioned, despite the advances in camera quality.&#xD;
&#xD;
      The study will aim to recruit a sample size of approximately 100 patients. Adult patients&#xD;
      scheduled for fluorescein angiography at the Kresge Eye Institute will be recruited into the&#xD;
      study by one of the study members if they meet inclusion and exclusion criteria. Once a&#xD;
      patient has consented to participate in the study, they will be randomized to receive either&#xD;
      a 250mg or 500mg dose of intravenous fluorescein with their fluorescein angiography&#xD;
      procedure. All fluorescein angiograms will be done only if clinically indicated, and&#xD;
      therefore the patient will not be placed at any increased risk by participating in this&#xD;
      study. If a participant returns for a repeat fluorescein angiogram within the next four&#xD;
      months, they will receive the dose (250mg or 500mg) which they did not receive with their&#xD;
      previous angiogram. Patients who experience an adverse reaction during their first angiogram&#xD;
      will be removed from the study in order to prevent a patient who had an adverse reaction with&#xD;
      a half-dose from receiving a full-dose with a subsequent procedure. The photographer will&#xD;
      adjust the image brightness settings in order to create the &quot;best possible&quot; image for each&#xD;
      patient, and there will be no change between procedures with the 250mg and 500mg doses. A&#xD;
      single camera (Optos) will be used for each patient in the study.&#xD;
&#xD;
      Data collection will be obtained from the patient, the imaging procedure, and the patient's&#xD;
      electronic medical records at the Kresge Eye Institute. Information to be collected includes&#xD;
      age, gender, race, visual acuity, and ophthalmologic medical history. The timing and quality&#xD;
      of images at different phases of fluorescein angiography will be compared between 500mg and&#xD;
      250mg doses in each eye using objective and subjective measures. Subjective criteria will&#xD;
      include grading of the images by a panel of masked retinal surgeons and residents. Grading&#xD;
      will look at specific factors of a fluorescein angiography such as macula detail,&#xD;
      macrovasculature, and microvasculature. These subjective criteria will then be used to&#xD;
      determine whether any appreciable difference exists in the image quality between 250mg and&#xD;
      500mg doses of intravenous fluorescein given prior to Optos fluorescein angiography.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Additional data may be required once preliminary data is analyzed.&#xD;
  </why_stopped>
  <start_date type="Actual">April 5, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2020</completion_date>
  <primary_completion_date type="Actual">July 17, 2019</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>
    <intervention_model_description>Patients will be randomly assigned to receive either a half-dose (250mg) or a full-dose (500mg) of intravenous fluorescein prior to their angiography procedure. If they return for a second fluorescein angiography study during the proceeding four months, they will receive the dose of fluorescein (250mg or 500mg) which they did not receive during their first study. Images will be evaluated subjectively by a masked panel of retinal surgeons for image quality, and image quality will be compared between images that are full dose and images that are half dose.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The primary outcomes assessors will be retinal surgeons and residents, masked to the dosing of fluorescein. They will assess the subjective quality of images.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Subjective comparison of image quality between full-dose and half-dose fluorescein angiography performed on the same patient.</measure>
    <time_frame>Six months.</time_frame>
    <description>Participants who receive two clinically-indicated fluorescein angiography procedures within the time frame of the study will receive both doses of Fluorescein Na (250mg and 500mg). These two images will then be compared to each other in terms of image quality by a team of masked retinal surgeons.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Subjective comparison of image quality between full-dose and half-dose fluorescein angiography among all patients enrolled in the study.</measure>
    <time_frame>One month.</time_frame>
    <description>All of the images obtained during the patient recruitment phase of the study will be evaluated subjectively in terms of image quality by a panel of masked retinal surgeons. The images will then be compared between patients to determine if there is a subjective difference in image quality between a 250mg and 500mg dose.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>Fluorescein Angiography</condition>
  <arm_group>
    <arm_group_label>Full-Dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this arm will receive Fluorescein Na 10% Inj 500mg pushed over several seconds one time, prior to their fluorescein angiogram. If they return for a second (clinically indicated) angiogram, they will receive Fluorescein Na 10% Inj 250mg pushed over several seconds one time.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Half-Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm will receive Fluorescein Na 10% Inj 250mg pushed over several seconds one time, prior to their fluorescein angiogram. If they return for a second (clinically indicated) angiogram, they will receive Fluorescein Na 10% Inj 500mg pushed over several seconds one time.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorescein Na 10% Inj 500mg</intervention_name>
    <description>Full-dose intravenous Fluorescein Na prior to fluorescein angiography.</description>
    <arm_group_label>Full-Dose</arm_group_label>
    <arm_group_label>Half-Dose</arm_group_label>
    <other_name>AK-Fluor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorescein Na 10% Inj 250mg</intervention_name>
    <description>Half-dose intravenous Fluorescein Na prior to fluorescein angiography.</description>
    <arm_group_label>Full-Dose</arm_group_label>
    <arm_group_label>Half-Dose</arm_group_label>
    <other_name>AK-Fluor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients scheduled for fluorescein angiography at Kresge Eye Institute.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with known major profusion defects on fluorescein angiography.&#xD;
&#xD;
          -  Patients with prior adverse reactions to fluorescein angiography.&#xD;
&#xD;
          -  Patients with significant photophobia as judged by the photographer.&#xD;
&#xD;
          -  Patients with visually significant cataracts.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>120 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gary W Abrams, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kresge Eye Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kresge Eye Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Xu K, Tzankova V, Li C, Sharma S. Intravenous fluorescein angiography-associated adverse reactions. Can J Ophthalmol. 2016 Oct;51(5):321-325. doi: 10.1016/j.jcjo.2016.03.015. Epub 2016 Sep 3.</citation>
    <PMID>27769320</PMID>
  </reference>
  <reference>
    <citation>Moosbrugger KA, Sheidow TG. Evaluation of the side effects and image quality during fluorescein angiography comparing 2 mL and 5 mL sodium fluorescein. Can J Ophthalmol. 2008 Oct;43(5):571-5. doi: 10.3129/i08-122.</citation>
    <PMID>18982034</PMID>
  </reference>
  <reference>
    <citation>Nicholson BP, Nigam D, Miller D, Agron E, Dalal M, Jacobs-El N, da Rocha Lima B, Cunningham D, Nussenblatt R, Sen HN. Comparison of wide-field fluorescein angiography and 9-field montage angiography in uveitis. Am J Ophthalmol. 2014 Mar;157(3):673-7. doi: 10.1016/j.ajo.2013.12.005. Epub 2013 Dec 7.</citation>
    <PMID>24321475</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>March 13, 2020</last_update_submitted>
  <last_update_submitted_qc>March 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>fluorescein</keyword>
  <keyword>angiography</keyword>
  <patient_data>
    <sharing_ipd>No</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/NCT03244982
org study id: 23897543
nct id: NCT03244982
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Fluorescein angiography is a common procedure used in ophthalmology to diagnose and monitor
      diseases of the eye. The standard dose of fluorescein dye used in fluorescein angiography is
      500mg. It is common practice to give patients who have previously had an adverse reaction to
      fluorescein dye a half-dose, or 250mg, of fluorescein. It has been determined by our
      institution that anecdotally, there is no difference in image quality between the images
      created by a half-dose of fluorescein versus a full dose of fluorescein. Therefore, this
      study seeks to determine whether these doses are actually equivalent in terms of image
      quality. Patients who consent to participate in the study will be randomized to receive
      either a half or a full dose of intravenous fluorescein, and their images will be compared
      subjectively using a masked team of retinal surgeons and residents. We hypothesize that there
      will be no significant difference between the images obtained using a half-dose versus a full
      dose of intravenous fluorescein.
Fluorescein angiography is a common procedure used in ophthalmology to diagnose and monitor
      diseases of the retinal and choroidal blood vessels. The most commonly seen adverse reactions
      to fluorescein angiography include nausea, vomiting, and urticaria. More severe reactions
      such as anaphylaxis are rare, occurring in only 1 of 2247 patients (0.4%) in a recent
      retrospective study. The standard dose of intravenous fluorescein used for fluorescein
      angiography is 500mg given intravenously in a 10% or 25% solution. One study from 2008
      attempted to compare a 200mg dose versus a 500mg dose of intravenous fluorescein, and found
      that 200mg produced inferior image quality. However, the quality of the cameras used for
      fluorescein angiography has improved significantly in the last 10 years, and the scanning
      laser ophthalmoscope currently used for fluorescein angiography in our clinic (Optos) is
      significantly more effective than the fundus camera used in the 2008 study (Topcon). The
      scanning laser ophthalmoscope uses a fundamentally different imaging technique than the
      traditional fundus camera, with a much narrower illumination source, and has been shown to be
      significantly more sensitive in the detection of retinal vascular leakage.

      A commonly used method for preventing adverse reactions in patients who have previously had
      an adverse reaction to intravenous fluorescein is to use a 250mg dose instead of the standard
      500mg dose, despite the lack of evidence to this effect. In our anecdotal experience, a 250mg
      dose of intravenous fluorescein, used in patients whom have previously experienced an adverse
      reaction, has produced images of equivalent quality to the images produced using a full 500mg
      dose. To our knowledge, no study has compared a 500mg dose of intravenous fluorescein with a
      lower dose since the 2008 study previously mentioned, despite the advances in camera quality.

      The study will aim to recruit a sample size of approximately 100 patients. Adult patients
      scheduled for fluorescein angiography at the Kresge Eye Institute will be recruited into the
      study by one of the study members if they meet inclusion and exclusion criteria. Once a
      patient has consented to participate in the study, they will be randomized to receive either
      a 250mg or 500mg dose of intravenous fluorescein with their fluorescein angiography
      procedure. All fluorescein angiograms will be done only if clinically indicated, and
      therefore the patient will not be placed at any increased risk by participating in this
      study. If a participant returns for a repeat fluorescein angiogram within the next four
      months, they will receive the dose (250mg or 500mg) which they did not receive with their
      previous angiogram. Patients who experience an adverse reaction during their first angiogram
      will be removed from the study in order to prevent a patient who had an adverse reaction with
      a half-dose from receiving a full-dose with a subsequent procedure. The photographer will
      adjust the image brightness settings in order to create the "best possible" image for each
      patient, and there will be no change between procedures with the 250mg and 500mg doses. A
      single camera (Optos) will be used for each patient in the study.

      Data collection will be obtained from the patient, the imaging procedure, and the patient's
      electronic medical records at the Kresge Eye Institute. Information to be collected includes
      age, gender, race, visual acuity, and ophthalmologic medical history. The timing and quality
      of images at different phases of fluorescein angiography will be compared between 500mg and
      250mg doses in each eye using objective and subjective measures. Subjective criteria will
      include grading of the images by a panel of masked retinal surgeons and residents. Grading
      will look at specific factors of a fluorescein angiography such as macula detail,
      macrovasculature, and microvasculature. These subjective criteria will then be used to
      determine whether any appreciable difference exists in the image quality between 250mg and
      500mg doses of intravenous fluorescein given prior to Optos fluorescein angiography.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be randomly assigned to receive either a half-dose (250mg) or a full-dose (500mg) of intravenous fluorescein prior to their angiography procedure. If they return for a second fluorescein angiography study during the proceeding four months, they will receive the dose of fluorescein (250mg or 500mg) which they did not receive during their first study. Images will be evaluated subjectively by a masked panel of retinal surgeons for image quality, and image quality will be compared between images that are full dose and images that are half dose.
primary purpose: Diagnostic
masking: Single (Outcomes Assessor)
masking description: The primary outcomes assessors will be retinal surgeons and residents, masked to the dosing of fluorescein. They will assess the subjective quality of images.
measure: Subjective comparison of image quality between full-dose and half-dose fluorescein angiography performed on the same patient.
time frame: Six months.
description: Participants who receive two clinically-indicated fluorescein angiography procedures within the time frame of the study will receive both doses of Fluorescein Na (250mg and 500mg). These two images will then be compared to each other in terms of image quality by a team of masked retinal surgeons.
measure: Subjective comparison of image quality between full-dose and half-dose fluorescein angiography among all patients enrolled in the study.
time frame: One month.
description: All of the images obtained during the patient recruitment phase of the study will be evaluated subjectively in terms of image quality by a panel of masked retinal surgeons. The images will then be compared between patients to determine if there is a subjective difference in image quality between a 250mg and 500mg dose.
arm group label: Full-Dose
arm group type: Active Comparator
description: Participants in this arm will receive Fluorescein Na 10% Inj 500mg pushed over several seconds one time, prior to their fluorescein angiogram. If they return for a second (clinically indicated) angiogram, they will receive Fluorescein Na 10% Inj 250mg pushed over several seconds one time.
arm group label: Half-Dose
arm group type: Experimental
description: Participants in this arm will receive Fluorescein Na 10% Inj 250mg pushed over several seconds one time, prior to their fluorescein angiogram. If they return for a second (clinically indicated) angiogram, they will receive Fluorescein Na 10% Inj 500mg pushed over several seconds one time.
intervention type: Drug
intervention name: Fluorescein Na 10% Inj 500mg
description: Full-dose intravenous Fluorescein Na prior to fluorescein angiography.
arm group label: Full-Dose
arm group label: Half-Dose
other name: AK-Fluor
intervention type: Drug
intervention name: Fluorescein Na 10% Inj 250mg
description: Half-dose intravenous Fluorescein Na prior to fluorescein angiography.
arm group label: Full-Dose
arm group label: Half-Dose
other name: AK-Fluor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 120 Years
healthy volunteers: No
last name: Gary W Abrams, MD
role: Principal Investigator
affiliation: Kresge Eye Institute
facility: 
country: United States
citation: Xu K, Tzankova V, Li C, Sharma S. Intravenous fluorescein angiography-associated adverse reactions. Can J Ophthalmol. 2016 Oct;51(5):321-325. doi: 10.1016/j.jcjo.2016.03.015. Epub 2016 Sep 3.
PMID: 27769320
citation: Moosbrugger KA, Sheidow TG. Evaluation of the side effects and image quality during fluorescein angiography comparing 2 mL and 5 mL sodium fluorescein. Can J Ophthalmol. 2008 Oct;43(5):571-5. doi: 10.3129/i08-122.
PMID: 18982034
citation: Nicholson BP, Nigam D, Miller D, Agron E, Dalal M, Jacobs-El N, da Rocha Lima B, Cunningham D, Nussenblatt R, Sen HN. Comparison of wide-field fluorescein angiography and 9-field montage angiography in uveitis. Am J Ophthalmol. 2014 Mar;157(3):673-7. doi: 10.1016/j.ajo.2013.12.005. Epub 2013 Dec 7.
PMID: 24321475
responsible party type: Sponsor
sharing ipd: No