<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/NCT03246724</url>
  </required_header>
  <id_info>
    <org_study_id>H-36590</org_study_id>
    <nct_id>NCT03246724</nct_id>
  </id_info>
  <brief_title>Oral Versus Intravenous Sedation for Ocular Procedures</brief_title>
  <official_title>A Single-center, Randomized, Double-blind, Double-dummy, Parallel-group Study Comparing Oral Sedation to Intravenous Sedation for Ocular Procedures.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boston Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate patient satisfaction after eye surgery when given a&#xD;
      capsule compared to an intravenous (IV) dose of sedation (calming medication).&#xD;
&#xD;
      Each subject will be given a capsule and an IV in the hospital before their procedure starts,&#xD;
      however they will not know which one is the sedation route. Each subject will have their&#xD;
      planned surgical procedure as previously discussed with their doctor. After the procedure is&#xD;
      completed, the doctors will complete satisfaction surveys. The subject will also complete a&#xD;
      satisfaction survey during their regularly scheduled visit the day after surgery. Once the&#xD;
      subject completes this survey, their study participation will be complete.&#xD;
&#xD;
      The hypothesis is that there will be no difference in patient satisfaction when given a&#xD;
      capsule in comparison to IV sedation. If the results of the study support this hypothesis, a&#xD;
      capsule could be used in place of IV sedation. By using a capsule for ocular procedures, both&#xD;
      patients and the medical practice would benefit: patient would be able to eat before their&#xD;
      procedure, patient costs would be decreased, hospital costs would be reduced, and some of&#xD;
      these procedures would be given the option to move to a procedure room (freeing up operating&#xD;
      room time for other departments).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to compare patient satisfaction of oral triazolam to&#xD;
      IV midazolam when administered for ocular procedures. Midazolam is an FDA-approved&#xD;
      intravenous medication commonly used as a sedative for ocular procedures conducted in the&#xD;
      operating room. This study will compare the use of triazolam, an FDA-approved oral sedative&#xD;
      for the same types of ocular procedures, a purpose which has not fully been investigated. The&#xD;
      benzodiazepine triazolam was chosen as the oral medication due to its similarity to&#xD;
      midazolam. The similarities between midazolam and triazolam include similar half-life, risks,&#xD;
      and patient experience.The medication doses were chosen from current SOC use based on weight.&#xD;
      The lower dose for both medications are used for patients with a BMI less than 35 and the&#xD;
      higher dose is used for patients with a BMI greater than or equal to 35.&#xD;
&#xD;
      This is the first double-blind, prospective clinical trial that will compare IV and oral&#xD;
      sedation for multiple ocular sub-specialty procedures. The procedures to be investigated&#xD;
      include: cataract, retina, cornea, and glaucoma surgical groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2017</start_date>
  <completion_date type="Actual">November 30, 2019</completion_date>
  <primary_completion_date type="Actual">November 30, 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>Interventions: triazolam oral sedation with sodium chloride 0.9% IV placebo or microcrystalline cellulose oral placebo with midazolam IV sedation&#xD;
Subjects will be randomized (1:1) to one of the two study arms listed above. On the day of surgery, the subject, anesthesiologist/CRNA, and surgeon will be blinded to the treatment assignment. The anesthesiologist/CRNA or pre-operative nurses will administer the blinded oral medication approximately 30 minutes before the procedure beings. The anesthesiologist/CRNA will administer the blinded IV medication approximately 5 minutes before the procedure begins. At the completion of the procedure, the anesthesiologist/CRNA and the surgeon will complete a satisfaction survey. The subject will then return within 2 days for their first post-operative clinical visit and complete a satisfaction survey.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>The subject and their entire medical team (including the anesthesiologist and surgeon) will all be masked to the subject's randomized intervention group. The randomization groups will be assigned by the statistician who will be unmasked. All medications will be provided to the medical team on the day of the procedure completely masked. The clinical research coordinator, the clinical research assistant, and the pharmacy will be unmasked to the intervention group. Any member of the medical team can be unmasked at any time after the intervention is administered in the case of an emergency resulting in a serious adverse event or an unanticipated problem.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Patient Satisfaction</measure>
    <time_frame>The patient satisfaction survey was administered up to two days after surgery.</time_frame>
    <description>Patient satisfaction will be determined by completion of a 12 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per patient. Higher mean scores are associated with higher levels of satisfaction.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Surgeon Satisfaction</measure>
    <time_frame>The surgeon satisfaction survey will be administered immediately after the completion of the surgery. .</time_frame>
    <description>Surgeon satisfaction will be determined by completion of a 5 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per surgeon Higher mean scores are associated with higher levels of satisfaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction</measure>
    <time_frame>The anesthesiologist/CRNA satisfaction survey will be administered immediately after the completion of the surgical case.</time_frame>
    <description>Anesthesiologist/CRNA satisfaction will be determined by completion of a 5 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per anesthesiologist/CRNA. Higher mean scores are associated with higher levels of satisfaction.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants Requiring Additional Anesthesia Intervention</measure>
    <time_frame>Information regarding additional anesthesia intervention will be collected within 2 days of completion of the subjects surgical procedure.</time_frame>
    <description>The number of subjects in each arm that received additional anesthetic agents during the operative procedure after the initial sedation.</description>
  </other_outcome>
  <other_outcome>
    <measure>Surgical Complication Rates</measure>
    <time_frame>Information regarding surgical complications will be collected within 2 days of completion of the subjects surgical procedure.</time_frame>
    <description>The number of subjects in each arm that experienced a complication during the operative procedure after the initial sedation.</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">327</enrollment>
  <condition>Surgery</condition>
  <condition>Sedation</condition>
  <arm_group>
    <arm_group_label>Cataract Procedures</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The following ocular procedures will fall under this arm of the study:&#xD;
• Cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Retina Procedures</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The following ocular procedures will fall under this arm of the study:&#xD;
Pars plana vitrectomy&#xD;
Pars plana vitrectomy with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cornea Procedures</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The following ocular procedures will fall under this arm of the study:&#xD;
Descemet Stripping Endothelial Keratoplasty (DSEK)&#xD;
Cataracts with Descemet Stripping Endothelial Keratoplasty (DSEK)&#xD;
Descemet Membrane Endothelial Keratoplasty (DMEK)&#xD;
Cataracts with Descemet Membrane Endothelial Keratoplasty (DMEK)&#xD;
Conjunctival and/or corneal lesion excisions&#xD;
Pterygium&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Glaucoma Procedures</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The following ocular procedures will fall under this arm of the study:&#xD;
Ahmed valve&#xD;
Ahmed valve with cataracts&#xD;
Trabeculectomy&#xD;
Trabeculectomy with cataracts&#xD;
Baerveldt&#xD;
Baerveldt with cataracts&#xD;
Endocyclophotocoagulation&#xD;
Endocyclophotocoagulation with cataracts&#xD;
Istent&#xD;
Cataracts with istent&#xD;
Kahook&#xD;
Cataracts with kahook&#xD;
Cypass&#xD;
Cypass with cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Triazolam</intervention_name>
    <description>This will be used for oral sedation. This capsule or a microcrystalline cellulose placebo capsule will be administered depending on the randomized treatment group.&#xD;
Dose for BMI less than 35: 0.125 mg&#xD;
Dose for BMI greater than or equal to 35: 0.25 mg</description>
    <arm_group_label>Cataract Procedures</arm_group_label>
    <arm_group_label>Cornea Procedures</arm_group_label>
    <arm_group_label>Glaucoma Procedures</arm_group_label>
    <arm_group_label>Retina Procedures</arm_group_label>
    <other_name>Halcion</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>This will be used for intravenous sedation. This injection or sodium chloride 0.9% will be administered depending on the randomized treatment group.&#xD;
Dose for BMI less than 35: 1.0 mg&#xD;
Dose for BMI greater than or equal to 35: 2.0 mg</description>
    <arm_group_label>Cataract Procedures</arm_group_label>
    <arm_group_label>Cornea Procedures</arm_group_label>
    <arm_group_label>Glaucoma Procedures</arm_group_label>
    <arm_group_label>Retina Procedures</arm_group_label>
    <other_name>Versed</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Microcrystalline Cellulose</intervention_name>
    <description>This will be used for the oral placebo. This capsule or a triazolam capsule will be administered depending on the randomized treatment group.&#xD;
Dose for BMI less than 35: 1 capsule&#xD;
Dose for BMI greater than or equal to 35: 2 capsule</description>
    <arm_group_label>Cataract Procedures</arm_group_label>
    <arm_group_label>Cornea Procedures</arm_group_label>
    <arm_group_label>Glaucoma Procedures</arm_group_label>
    <arm_group_label>Retina Procedures</arm_group_label>
    <other_name>Avicel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium chloride 0.9%</intervention_name>
    <description>This will be used for the intravenous placebo.This injection or midazolam will be administered depending on the randomized treatment group.&#xD;
Dose for BMI less than 35: volume to match volume of active intravenous medication&#xD;
Dose for BMI greater than or equal to 35: volume to match volume of active intravenous medication</description>
    <arm_group_label>Cataract Procedures</arm_group_label>
    <arm_group_label>Cornea Procedures</arm_group_label>
    <arm_group_label>Glaucoma Procedures</arm_group_label>
    <arm_group_label>Retina Procedures</arm_group_label>
    <other_name>Normal Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18 years or older&#xD;
&#xD;
          2. Ability to speak and read in English or Spanish or Haitian Creole&#xD;
&#xD;
          3. Subjects able to consent for themselves&#xD;
&#xD;
          4. Outpatient surgical plan for any of the following procedures:&#xD;
&#xD;
               -  Cataract surgery: cataracts&#xD;
&#xD;
               -  Retina: pars plana vitrectomy, pars plana vitrectomy with cataracts, epiretinal&#xD;
                  membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal&#xD;
&#xD;
               -  Cornea: descemet stripping endothelial keratopathy, cataracts with descemet&#xD;
                  stripping endothelial keratopathy, descemet membrane endothelial keratoplasty,&#xD;
                  cataracts with descemet membrane endothelial keratoplasty, conjunctival and/or&#xD;
                  corneal lesion excisions, pterygium&#xD;
&#xD;
               -  Glaucoma: ahmed valve, ahmed valve with cataracts,trabeculectomy, trabeculectomy&#xD;
                  with cataracts, baerveldt, baerveldt with cataracts, endocyclophotocoagulation,&#xD;
                  endocyclophotocoagulation with cataracts, istent, istent with cataracts, kahook,&#xD;
                  kahook with cataracts, cypass, cypass with cataracts&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Surgical plan which includes general anesthesia&#xD;
&#xD;
          2. Hypersensitivity or allergy to benzodiazepines&#xD;
&#xD;
          3. Women who are pregnant, have a positive pregnancy test on the day of surgery, refuse a&#xD;
             pregnancy test, or are nursing&#xD;
&#xD;
          4. Previous delirium after anesthesia with a benzodiazepine&#xD;
&#xD;
          5. Subjects 70 years of age or older who fail the delirium pre-screening questionnaire as&#xD;
             shown in Appendix Section 15.6&#xD;
&#xD;
          6. Currently experiencing the effects of drug/alcohol&#xD;
&#xD;
          7. Current oral/IV regimen of any medication inhibiting cytochrome P450 3A which includes&#xD;
             ketoconazole, itraconazole, nefazodone, ritonavir, indinavir, nelavir, saquinavir, and&#xD;
             lopinavir&#xD;
&#xD;
          8. Subjects already enrolled in this study for the fellow eye&#xD;
&#xD;
          9. Subjects enrolled in a clinical trial with an investigational drug within the past 3&#xD;
             months&#xD;
&#xD;
         10. Failed anesthesia clearance to receive a benzodiazepine&#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>Manju Subramanian, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Boston Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boston Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=575d8bf0-7af7-427c-a231-966e2a5e070d</url>
    <description>Midazolam Drug Label Information</description>
  </link>
  <link>
    <url>http://www.advancingsurgicalcare.com/reducinghealthcarecosts/costsavings/healthcarebluebookstudy</url>
    <description>Commercial Insurance Costs Savings in Ambulatory Surgery Center 2016</description>
  </link>
  <reference>
    <citation>Ianchulev T, Litoff D, Ellinger D, Stiverson K, Packer M. Office-Based Cataract Surgery: Population Health Outcomes Study of More than 21 000 Cases in the United States. Ophthalmology. 2016 Apr;123(4):723-8. doi: 10.1016/j.ophtha.2015.12.020. Epub 2016 Jan 22.</citation>
    <PMID>26804760</PMID>
  </reference>
  <reference>
    <citation>American Society of Anesthesiologists Committee. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures: an updated report by the American Society of Anesthesiologists Committee on Standards and Practice Parameters. Anesthesiology. 2011 Mar;114(3):495-511. doi: 10.1097/ALN.0b013e3181fcbfd9. No abstract available.</citation>
    <PMID>21307770</PMID>
  </reference>
  <reference>
    <citation>Campbell J. Intravenous cannulation: potential complications. Prof Nurse. 1997 May;12(8 Suppl):S10-3.</citation>
    <PMID>9180592</PMID>
  </reference>
  <reference>
    <citation>Committee on Standards and Practice Parameters; Apfelbaum JL, Connis RT, Nickinovich DG; American Society of Anesthesiologists Task Force on Preanesthesia Evaluation; Pasternak LR, Arens JF, Caplan RA, Connis RT, Fleisher LA, Flowerdew R, Gold BS, Mayhew JF, Nickinovich DG, Rice LJ, Roizen MF, Twersky RS. Practice advisory for preanesthesia evaluation: an updated report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. Anesthesiology. 2012 Mar;116(3):522-38. doi: 10.1097/ALN.0b013e31823c1067. No abstract available.</citation>
    <PMID>22273990</PMID>
  </reference>
  <results_reference>
    <citation>Fung D, Cohen M, Stewart S, Davies A. Can the Iowa Satisfaction with Anesthesia Scale be used to measure patient satisfaction with cataract care under topical local anesthesia and monitored sedation at a community hospital? Anesth Analg. 2005 Jun;100(6):1637-1643. doi: 10.1213/01.ANE.0000154203.00434.23.</citation>
    <PMID>15920188</PMID>
  </results_reference>
  <results_reference>
    <citation>Erdurmus M, Aydin B, Usta B, Yagci R, Gozdemir M, Totan Y. Patient comfort and surgeon satisfaction during cataract surgery using topical anesthesia with or without dexmedetomidine sedation. Eur J Ophthalmol. 2008 May-Jun;18(3):361-7. doi: 10.1177/112067210801800308.</citation>
    <PMID>18465717</PMID>
  </results_reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <results_first_submitted>July 20, 2020</results_first_submitted>
  <results_first_submitted_qc>August 7, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 19, 2020</results_first_posted>
  <last_update_submitted>August 7, 2020</last_update_submitted>
  <last_update_submitted_qc>August 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ocular surgery</keyword>
  <keyword>Intravenous sedation</keyword>
  <keyword>Oral sedation</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Triazolam</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 28, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/24/NCT03246724/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients were recruited from October 26th, 2017 to November 30th, 2019 at the outpatient eye clinic, Ophthalmology Department, Boston Medical Center.</recruitment_details>
      <pre_assignment_details>Out of 327 patients enrolled, 283 completed study participation and 44 patients did not complete study participation as they were dropped or withdrew from the study. 22 patients were dropped before randomization and 22 patients discontinued from study after randomization due to reasons seen in the participant flow table.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cataract Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
• Cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
        </group>
        <group group_id="P2">
          <title>Retina Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
Pars plana vitrectomy (PPV)&#xD;
PPV with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
        </group>
        <group group_id="P3">
          <title>Cornea Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
Descemet Stripping Endothelial Keratoplasty (DSEK)&#xD;
Cataracts with DSEK&#xD;
Descemet Membrane Endothelial Keratoplasty (DMEK)&#xD;
Cataracts with DMEK&#xD;
Conjunctival and/or corneal lesion excisions&#xD;
Pterygium&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
        </group>
        <group group_id="P4">
          <title>Glaucoma Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
Ahmed valve&#xD;
Ahmed valve with cataracts&#xD;
Trabeculectomy&#xD;
Trabeculectomy with cataracts&#xD;
Baerveldt&#xD;
Baerveldt with cataracts&#xD;
Endocyclophotocoagulation&#xD;
Endocyclophotocoagulation with cataracts&#xD;
Istent&#xD;
Cataracts with istent&#xD;
Kahook&#xD;
Cataracts with kahook&#xD;
Cypass&#xD;
Cypass with cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="99"/>
                <participants group_id="P2" count="91"/>
                <participants group_id="P3" count="85"/>
                <participants group_id="P4" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="85"/>
                <participants group_id="P2" count="84"/>
                <participants group_id="P3" count="70"/>
                <participants group_id="P4" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ineligible on day of surgery</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study completed before surgical date</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Transferred to other arm</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unable to obtain medication timely</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Re-consented to participate</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The data displays information for participants that complete study participation.</population>
      <group_list>
        <group group_id="B1">
          <title>Cataract Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
• Cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation&#xD;
Triazolam or microcrystalline cellulose oral placebo: Administered 30 minutes prior to surgery.&#xD;
Dose for BMI less than 35: 0.125 mg Dose for BMI greater than or equal to 35: 0.25 mg&#xD;
Midazolam or sodium chloride 0.9%: Administered 5 minutes prior to surgery Dose for BMI less than 35: 1.0 mg Dose for BMI greater than or equal to 35: 2.0 mg</description>
        </group>
        <group group_id="B2">
          <title>Retina Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
Pars plana vitrectomy&#xD;
Pars plana vitrectomy with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation&#xD;
Triazolam or microcrystalline cellulose oral placebo: Administered 30 minutes prior to surgery.&#xD;
Dose for BMI less than 35: 0.125 mg Dose for BMI greater than or equal to 35: 0.25 mg&#xD;
Midazolam or sodium chloride 0.9%: Administered 5 minutes prior to surgery Dose for BMI less than 35: 1.0 mg Dose for BMI greater than or equal to 35: 2.0 mg</description>
        </group>
        <group group_id="B3">
          <title>Cornea Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
Descemet Stripping Endothelial Keratoplasty (DSEK)&#xD;
Cataracts with DSEK&#xD;
Descemet Membrane Endothelial Keratoplasty(DMEK)&#xD;
Cataracts with DMEK&#xD;
Conjunctival and/or corneal lesion excisions&#xD;
Pterygium&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation&#xD;
Triazolam or oral placebo: Administered 30 minutes prior to surgery Dose for BMI less than 35: 0.125 mg Dose for BMI greater than or equal to 35: 0.25 mg&#xD;
Midazolam or sodium chloride 0.9%: Administered 5 minutes prior to surgery Dose for BMI less than 35: 1.0 mg Dose for BMI greater than or equal to 35: 2.0 mg</description>
        </group>
        <group group_id="B4">
          <title>Glaucoma Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
Ahmed valve&#xD;
Ahmed valve with cataracts&#xD;
Trabeculectomy&#xD;
Trabeculectomy with cataracts&#xD;
Baerveldt&#xD;
Baerveldt with cataracts&#xD;
Endocyclophotocoagulation (ECP)&#xD;
ECP with cataracts&#xD;
Istent&#xD;
Cataracts with istent&#xD;
Kahook&#xD;
Cataracts with kahook&#xD;
Cypass&#xD;
Cypass with cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% IV placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation&#xD;
Triazolam or placebo: Given 30 minutes prior to surgery Dose for BMI less than 35: 0.125 mg Dose for BMI greater than or equal to 35: 0.25 mg&#xD;
Midazolam or placebo: Given 5 minutes prior to surgery Dose for BMI less than 35: 1.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="85"/>
            <count group_id="B2" value="84"/>
            <count group_id="B3" value="70"/>
            <count group_id="B4" value="44"/>
            <count group_id="B5" value="283"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.59" spread="9.14"/>
                    <measurement group_id="B2" value="57.02" spread="12.65"/>
                    <measurement group_id="B3" value="49.96" spread="14.99"/>
                    <measurement group_id="B4" value="66.52" spread="11.32"/>
                    <measurement group_id="B5" value="59.67" spread="13.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="20"/>
                    <measurement group_id="B5" value="124"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="47"/>
                    <measurement group_id="B4" value="24"/>
                    <measurement group_id="B5" value="159"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="42"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="98"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="58"/>
                    <measurement group_id="B2" value="60"/>
                    <measurement group_id="B3" value="26"/>
                    <measurement group_id="B4" value="32"/>
                    <measurement group_id="B5" value="176"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="28"/>
                    <measurement group_id="B5" value="109"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="41"/>
                    <measurement group_id="B4" value="13"/>
                    <measurement group_id="B5" value="112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Language</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>English</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="56"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="26"/>
                    <measurement group_id="B5" value="158"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Spanish</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="42"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="97"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Haitian Creole</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31.12" spread="6.44"/>
                    <measurement group_id="B2" value="29.86" spread="6.1"/>
                    <measurement group_id="B3" value="29.91" spread="5.48"/>
                    <measurement group_id="B4" value="29.6" spread="5.94"/>
                    <measurement group_id="B5" value="29.77" spread="5.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Patient Satisfaction</title>
        <description>Patient satisfaction will be determined by completion of a 12 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per patient. Higher mean scores are associated with higher levels of satisfaction.</description>
        <time_frame>The patient satisfaction survey was administered up to two days after surgery.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cataract Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
• Cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O2">
            <title>Retina Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Pars plana vitrectomy (PPV)&#xD;
PPV with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O3">
            <title>Cornea Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Descemet Stripping Endothelial Keratoplasty (DSEK)&#xD;
Cataracts with DSEK&#xD;
Descemet Membrane Endothelial Keratoplasty (DMEK)&#xD;
Cataracts with DMEK&#xD;
Conjunctival and/or corneal lesion excisions&#xD;
Pterygium&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O4">
            <title>Glaucoma Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Ahmed valve&#xD;
Ahmed valve with cataracts&#xD;
Trabeculectomy&#xD;
Trabeculectomy with cataracts&#xD;
Baerveldt&#xD;
Baerveldt with cataracts&#xD;
Endocyclophotocoagulation&#xD;
Endocyclophotocoagulation with cataracts&#xD;
Istent&#xD;
Cataracts with istent&#xD;
Kahook&#xD;
Cataracts with kahook&#xD;
Cypass&#xD;
Cypass with cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Satisfaction</title>
          <description>Patient satisfaction will be determined by completion of a 12 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per patient. Higher mean scores are associated with higher levels of satisfaction.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
                <count group_id="O2" value="84"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.37" spread="0.57"/>
                    <measurement group_id="O2" value="5.23" spread="0.72"/>
                    <measurement group_id="O3" value="5.37" spread="0.68"/>
                    <measurement group_id="O4" value="5.05" spread="0.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Testable hypothesis: Patient satisfaction mean will be non-inferior when given oral triazolam in comparison to IV midazolam during all basic cataracts, retina, cornea, and glaucoma ocular procedures.&#xD;
Null hypothesis: The null hypothesis is that the oral sedation group will have a primary endpoint mean equal to or less than that of the IV sedation group by the non-inferiority margin or more.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>A non-inferiority margin of 0.5, will assure that, if non-inferiority is proven, the mean patient satisfaction with oral sedation will correspond to scores corresponding to satisfied or higher. A 0.5 margin to be considered clinically similar enough to declare non-inferiority because it allows for expected patient satisfaction variability, and demonstrates ample justification for providers to offer oral sedation as a safe alternative.</non_inferiority_desc>
            <p_value>&lt;0.05</p_value>
            <p_value_desc>As a sensitivity analysis, an ANCOVA model will be fit to the data adjusting for factors that are out of balance following randomization. The mean difference between the adjusted means will be calculated.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>If lower bound of the 90% two-sided Confidence Interval of mean difference is higher than -0.5, the oral sedation will be deemed non-inferior to IV.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Surgeon Satisfaction</title>
        <description>Surgeon satisfaction will be determined by completion of a 5 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per surgeon Higher mean scores are associated with higher levels of satisfaction.</description>
        <time_frame>The surgeon satisfaction survey will be administered immediately after the completion of the surgery. .</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cataract Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
• Cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O2">
            <title>Retina Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Pars plana vitrectomy (PPV)&#xD;
PPV with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O3">
            <title>Cornea Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Descemet Stripping Endothelial Keratoplasty (DSEK)&#xD;
Cataracts with DSEK&#xD;
Descemet Membrane Endothelial Keratoplasty (DMEK)&#xD;
Cataracts with DMEK&#xD;
Conjunctival and/or corneal lesion excisions&#xD;
Pterygium&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O4">
            <title>Glaucoma Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Ahmed valve&#xD;
Ahmed valve with cataracts&#xD;
Trabeculectomy&#xD;
Trabeculectomy with cataracts&#xD;
Baerveldt&#xD;
Baerveldt with cataracts&#xD;
Endocyclophotocoagulation&#xD;
Endocyclophotocoagulation with cataracts&#xD;
Istent&#xD;
Cataracts with istent&#xD;
Kahook&#xD;
Cataracts with kahook&#xD;
Cypass&#xD;
Cypass with cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
        </group_list>
        <measure>
          <title>Surgeon Satisfaction</title>
          <description>Surgeon satisfaction will be determined by completion of a 5 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per surgeon Higher mean scores are associated with higher levels of satisfaction.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
                <count group_id="O2" value="84"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.28" spread="0.97"/>
                    <measurement group_id="O2" value="5.57" spread="0.84"/>
                    <measurement group_id="O3" value="5.34" spread="0.95"/>
                    <measurement group_id="O4" value="4.6" spread="1.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis: Mean surgeon satisfaction score for oral triazolam will be statistically significant in comparison to mean surgeon satisfaction score for IV midazolam during all cataracts, retina, cornea, and glaucoma ocular procedures.&#xD;
Alternate hypothesis: Mean surgeon satisfaction score for oral triazolam will not be statistically significant in comparison to mean surgeon satisfaction score for IV midazolam during all cataracts, retina, cornea, and glaucoma ocular procedures.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>A non-inferiority margin of 0.5, will assure that, if non-inferiority is proven, the mean patient satisfaction with oral sedation will correspond to scores corresponding to satisfied or higher. We determined a 0.5 margin to be considered clinically similar enough to declare non-inferiority because it allows for expected patient satisfaction variability, and demonstrates ample justification for providers to offer oral sedation as a safe alternative.</non_inferiority_desc>
            <p_value>&lt;0.05</p_value>
            <p_value_desc>Surgeon satisfaction score will be independently analyzed. Summary statistics including, means, standard deviations along with points estimates of the mean difference between the two groups and 90% Confidence Intervals.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>If lower bound of the 90% two-sided Confidence Interval of mean difference is higher than -0.5, oral sedation will be deemed non-inferior to IV.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction</title>
        <description>Anesthesiologist/CRNA satisfaction will be determined by completion of a 5 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per anesthesiologist/CRNA. Higher mean scores are associated with higher levels of satisfaction.</description>
        <time_frame>The anesthesiologist/CRNA satisfaction survey will be administered immediately after the completion of the surgical case.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cataract Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
• Cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O2">
            <title>Retina Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Pars plana vitrectomy (PPV)&#xD;
PPV with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O3">
            <title>Cornea Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Descemet Stripping Endothelial Keratoplasty (DSEK)&#xD;
Cataracts with DSEK&#xD;
Descemet Membrane Endothelial Keratoplasty (DMEK)&#xD;
Cataracts with DMEK&#xD;
Conjunctival and/or corneal lesion excisions&#xD;
Pterygium&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O4">
            <title>Glaucoma Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Ahmed valve&#xD;
Ahmed valve with cataracts&#xD;
Trabeculectomy&#xD;
Trabeculectomy with cataracts&#xD;
Baerveldt&#xD;
Baerveldt with cataracts&#xD;
Endocyclophotocoagulation&#xD;
Endocyclophotocoagulation with cataracts&#xD;
Istent&#xD;
Cataracts with istent&#xD;
Kahook&#xD;
Cataracts with kahook&#xD;
Cypass&#xD;
Cypass with cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
        </group_list>
        <measure>
          <title>Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction</title>
          <description>Anesthesiologist/CRNA satisfaction will be determined by completion of a 5 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per anesthesiologist/CRNA. Higher mean scores are associated with higher levels of satisfaction.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
                <count group_id="O2" value="84"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.16" spread="0.96"/>
                    <measurement group_id="O2" value="5.14" spread="0.94"/>
                    <measurement group_id="O3" value="5.33" spread="0.81"/>
                    <measurement group_id="O4" value="4.9" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis: Mean anesthesiologist/CRNA satisfaction score for oral triazolam will be statistically significant in comparison to mean anesthesiologist/CRNA satisfaction score for IV midazolam during cataracts, retina, cornea, and glaucoma procedures.&#xD;
Alternate hypothesis:Mean anesthesiologist/CRNA satisfaction score for oral triazolam will not be statistically significant in comparison to mean satisfaction score for IV midazolam during cataracts, retina, cornea, and glaucoma procedures.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>A non-inferiority margin of 0.5, will assure that, if non-inferiority is proven, the mean patient satisfaction with oral sedation will correspond to scores corresponding to satisfied or higher. We determined a 0.5 margin to be considered clinically similar enough to declare non-inferiority because it allows for expected patient satisfaction variability, and demonstrates ample justification for providers to offer oral sedation as a safe alternative.</non_inferiority_desc>
            <p_value>&lt;0.05</p_value>
            <p_value_desc>Anesthesiologist/CRNA satisfaction score will be independently analyzed. Summary statistics including, means, standard deviations along with points estimates of the mean difference between the two groups and 90% Confidence Intervals.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>If lower bound of the 90% two-sided Confidence Interval of mean difference is higher than -0.5, the oral sedation will be deemed non-inferior to IV.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants Requiring Additional Anesthesia Intervention</title>
        <description>The number of subjects in each arm that received additional anesthetic agents during the operative procedure after the initial sedation.</description>
        <time_frame>Information regarding additional anesthesia intervention will be collected within 2 days of completion of the subjects surgical procedure.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cataract Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
• Cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O2">
            <title>Retina Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Pars plana vitrectomy (PPV)&#xD;
PPV with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O3">
            <title>Cornea Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Descemet Stripping Endothelial Keratoplasty (DSEK)&#xD;
Cataracts with DSEK&#xD;
Descemet Membrane Endothelial Keratoplasty (DMEK)&#xD;
Cataracts with DMEK&#xD;
Conjunctival and/or corneal lesion excisions&#xD;
Pterygium&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O4">
            <title>Glaucoma Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Ahmed valve&#xD;
Ahmed valve with cataracts&#xD;
Trabeculectomy&#xD;
Trabeculectomy with cataracts&#xD;
Baerveldt&#xD;
Baerveldt with cataracts&#xD;
Endocyclophotocoagulation&#xD;
Endocyclophotocoagulation with cataracts&#xD;
Istent&#xD;
Cataracts with istent&#xD;
Kahook&#xD;
Cataracts with kahook&#xD;
Cypass&#xD;
Cypass with cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Requiring Additional Anesthesia Intervention</title>
          <description>The number of subjects in each arm that received additional anesthetic agents during the operative procedure after the initial sedation.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
                <count group_id="O2" value="84"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="11"/>
                    <measurement group_id="O4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis:The total additional anesthesia interventions for oral triazolam will be statistically significant in comparison to additional anesthesia interventions for IV midazolam during cataracts, retina, cornea, and glaucoma procedures.&#xD;
Alternate hypothesis:The total additional anesthesia interventions for oral triazolam will not be statistically significant in comparison to additional anesthesia interventions for IV midazolam during cataracts, retina, cornea, and glaucoma procedures</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Additional anesthesia intervention will be using summary statistics including, counts and proportions along with point's estimates of the proportion difference between the two groups and 90% Confidence Intervals.</non_inferiority_desc>
            <p_value>&lt;0.05</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Surgical Complication Rates</title>
        <description>The number of subjects in each arm that experienced a complication during the operative procedure after the initial sedation.</description>
        <time_frame>Information regarding surgical complications will be collected within 2 days of completion of the subjects surgical procedure.</time_frame>
        <population>Data was not available for one participant in the cornea arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Cataract Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
• Cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O2">
            <title>Retina Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Pars plana vitrectomy (PPV)&#xD;
PPV with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O3">
            <title>Cornea Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Descemet Stripping Endothelial Keratoplasty (DSEK)&#xD;
Cataracts with DSEK&#xD;
Descemet Membrane Endothelial Keratoplasty (DMEK)&#xD;
Cataracts with DMEK&#xD;
Conjunctival and/or corneal lesion excisions&#xD;
Pterygium&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
          <group group_id="O4">
            <title>Glaucoma Procedures</title>
            <description>The following ocular procedures will fall under this arm of the study:&#xD;
Ahmed valve&#xD;
Ahmed valve with cataracts&#xD;
Trabeculectomy&#xD;
Trabeculectomy with cataracts&#xD;
Baerveldt&#xD;
Baerveldt with cataracts&#xD;
Endocyclophotocoagulation&#xD;
Endocyclophotocoagulation with cataracts&#xD;
Istent&#xD;
Cataracts with istent&#xD;
Kahook&#xD;
Cataracts with kahook&#xD;
Cypass&#xD;
Cypass with cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
          </group>
        </group_list>
        <measure>
          <title>Surgical Complication Rates</title>
          <description>The number of subjects in each arm that experienced a complication during the operative procedure after the initial sedation.</description>
          <population>Data was not available for one participant in the cornea arm.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
                <count group_id="O2" value="84"/>
                <count group_id="O3" value="69"/>
                <count group_id="O4" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis: The total surgical complications for oral triazolam will be statistically significant in comparison to total surgical complications for IV midazolam during all cataracts, retina, cornea, and glaucoma ocular procedures.&#xD;
Alternate hypothesis: The total surgical complications for oral triazolam will not be statistically significant in comparison to total surgical complications for IV midazolam during all cataracts, retina, cornea, and glaucoma ocular procedures.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Surgical complications will be using summary statistics including, counts and proportions along with point's estimates of the proportion difference between the two groups and 90% Confidence Intervals.</non_inferiority_desc>
            <p_value>&lt;0.05</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were noted during the surgery and up to two days after the surgery when the patient satisfaction survey was administered.</time_frame>
      <desc>The same definition of adverse events and serious adverse events as clinicaltrials.gov. With the exception of hypertension, all other adverse events were not related to a particular organ system and occurred as a result of the surgical procedure.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cataract Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
• Cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
        </group>
        <group group_id="E2">
          <title>Retina Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
Pars plana vitrectomy (PPV)&#xD;
PPV with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
        </group>
        <group group_id="E3">
          <title>Cornea Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
Descemet Stripping Endothelial Keratoplasty (DSEK)&#xD;
Cataracts with DSEK&#xD;
Descemet Membrane Endothelial Keratoplasty (DMEK)&#xD;
Cataracts with DMEK&#xD;
Conjunctival and/or corneal lesion excisions&#xD;
Pterygium&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
        </group>
        <group group_id="E4">
          <title>Glaucoma Procedures</title>
          <description>The following ocular procedures will fall under this arm of the study:&#xD;
Ahmed valve&#xD;
Ahmed valve with cataracts&#xD;
Trabeculectomy&#xD;
Trabeculectomy with cataracts&#xD;
Baerveldt&#xD;
Baerveldt with cataracts&#xD;
Endocyclophotocoagulation&#xD;
Endocyclophotocoagulation with cataracts&#xD;
Istent&#xD;
Cataracts with istent&#xD;
Kahook&#xD;
Cataracts with kahook&#xD;
Cypass&#xD;
Cypass with cataracts&#xD;
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:&#xD;
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo&#xD;
Microcrystalline cellulose oral placebo with midazolam intravenous sedation</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>In-patient Hospitalization</sub_title>
                <description>Patient experienced pain and unease during surgery, and nausea, and malaise after surgery. The intervention was in-patient hospitalization. SAE was unexpected and the severity grade of SAE was 3. SAE was resolved on day of surgery.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="85"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="84"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="70"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Pain During Surgery</sub_title>
                <description>The patient experienced pain and up to two days after surgery (in the eye, chest, back). The pain varied in severity and was self-reported by patients when the patient satisfaction survey was administered.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="15" subjects_affected="15" subjects_at_risk="84"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="70"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Nausea &amp; Vomiting Post-surgery</sub_title>
                <description>The patient experienced nausea and vomiting after surgery. This was self-reported, varied in severity, and was recorded when the patient satisfaction survey was administered.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="84"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Headache &amp; Dizziness</sub_title>
                <description>The patient experienced headache and/or dizziness after surgery. This was self-reported, varied in severity, and was recorded when the patient satisfaction survey was administered.</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="85"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="84"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="70"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <description>The patient experienced anxiety before and during surgery. This was self-reported, varied in severity, and was recorded on the day of the surgery.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <description>The patient experienced hypertension after surgery. This was self-reported, varied in severity, and was recorded when the patient satisfaction survey was administered.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Marissa Fiorello, Clinical Research Manager</name_or_title>
      <organization>Boston Medical Center</organization>
      <phone>617-414-8848</phone>
      <email>Marissa.Fiorello@bmc.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03246724
org study id: H-36590
nct id: NCT03246724
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to evaluate patient satisfaction after eye surgery when given a
      capsule compared to an intravenous (IV) dose of sedation (calming medication).

      Each subject will be given a capsule and an IV in the hospital before their procedure starts,
      however they will not know which one is the sedation route. Each subject will have their
      planned surgical procedure as previously discussed with their doctor. After the procedure is
      completed, the doctors will complete satisfaction surveys. The subject will also complete a
      satisfaction survey during their regularly scheduled visit the day after surgery. Once the
      subject completes this survey, their study participation will be complete.

      The hypothesis is that there will be no difference in patient satisfaction when given a
      capsule in comparison to IV sedation. If the results of the study support this hypothesis, a
      capsule could be used in place of IV sedation. By using a capsule for ocular procedures, both
      patients and the medical practice would benefit: patient would be able to eat before their
      procedure, patient costs would be decreased, hospital costs would be reduced, and some of
      these procedures would be given the option to move to a procedure room (freeing up operating
      room time for other departments).
The primary objective of this study is to compare patient satisfaction of oral triazolam to
      IV midazolam when administered for ocular procedures. Midazolam is an FDA-approved
      intravenous medication commonly used as a sedative for ocular procedures conducted in the
      operating room. This study will compare the use of triazolam, an FDA-approved oral sedative
      for the same types of ocular procedures, a purpose which has not fully been investigated. The
      benzodiazepine triazolam was chosen as the oral medication due to its similarity to
      midazolam. The similarities between midazolam and triazolam include similar half-life, risks,
      and patient experience.The medication doses were chosen from current SOC use based on weight.
      The lower dose for both medications are used for patients with a BMI less than 35 and the
      higher dose is used for patients with a BMI greater than or equal to 35.

      This is the first double-blind, prospective clinical trial that will compare IV and oral
      sedation for multiple ocular sub-specialty procedures. The procedures to be investigated
      include: cataract, retina, cornea, and glaucoma surgical groups.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Interventions: triazolam oral sedation with sodium chloride 0.9% IV placebo or microcrystalline cellulose oral placebo with midazolam IV sedation
Subjects will be randomized (1:1) to one of the two study arms listed above. On the day of surgery, the subject, anesthesiologist/CRNA, and surgeon will be blinded to the treatment assignment. The anesthesiologist/CRNA or pre-operative nurses will administer the blinded oral medication approximately 30 minutes before the procedure beings. The anesthesiologist/CRNA will administer the blinded IV medication approximately 5 minutes before the procedure begins. At the completion of the procedure, the anesthesiologist/CRNA and the surgeon will complete a satisfaction survey. The subject will then return within 2 days for their first post-operative clinical visit and complete a satisfaction survey.
primary purpose: Health Services Research
masking: Triple (Participant, Care Provider, Investigator)
masking description: The subject and their entire medical team (including the anesthesiologist and surgeon) will all be masked to the subject's randomized intervention group. The randomization groups will be assigned by the statistician who will be unmasked. All medications will be provided to the medical team on the day of the procedure completely masked. The clinical research coordinator, the clinical research assistant, and the pharmacy will be unmasked to the intervention group. Any member of the medical team can be unmasked at any time after the intervention is administered in the case of an emergency resulting in a serious adverse event or an unanticipated problem.
measure: Patient Satisfaction
time frame: The patient satisfaction survey was administered up to two days after surgery.
description: Patient satisfaction will be determined by completion of a 12 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per patient. Higher mean scores are associated with higher levels of satisfaction.
measure: Surgeon Satisfaction
time frame: The surgeon satisfaction survey will be administered immediately after the completion of the surgery. .
description: Surgeon satisfaction will be determined by completion of a 5 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per surgeon Higher mean scores are associated with higher levels of satisfaction.
measure: Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction
time frame: The anesthesiologist/CRNA satisfaction survey will be administered immediately after the completion of the surgical case.
description: Anesthesiologist/CRNA satisfaction will be determined by completion of a 5 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per anesthesiologist/CRNA. Higher mean scores are associated with higher levels of satisfaction.
measure: Number of Participants Requiring Additional Anesthesia Intervention
time frame: Information regarding additional anesthesia intervention will be collected within 2 days of completion of the subjects surgical procedure.
description: The number of subjects in each arm that received additional anesthetic agents during the operative procedure after the initial sedation.
measure: Surgical Complication Rates
time frame: Information regarding surgical complications will be collected within 2 days of completion of the subjects surgical procedure.
description: The number of subjects in each arm that experienced a complication during the operative procedure after the initial sedation.
arm group label: Cataract Procedures
arm group type: Experimental
description: The following ocular procedures will fall under this arm of the study:
• Cataracts
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo
Microcrystalline cellulose oral placebo with midazolam intravenous sedation
arm group label: Retina Procedures
arm group type: Experimental
description: The following ocular procedures will fall under this arm of the study:
Pars plana vitrectomy
Pars plana vitrectomy with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo
Microcrystalline cellulose oral placebo with midazolam intravenous sedation
arm group label: Cornea Procedures
arm group type: Experimental
description: The following ocular procedures will fall under this arm of the study:
Descemet Stripping Endothelial Keratoplasty (DSEK)
Cataracts with Descemet Stripping Endothelial Keratoplasty (DSEK)
Descemet Membrane Endothelial Keratoplasty (DMEK)
Cataracts with Descemet Membrane Endothelial Keratoplasty (DMEK)
Conjunctival and/or corneal lesion excisions
Pterygium
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo
Microcrystalline cellulose oral placebo with midazolam intravenous sedation
arm group label: Glaucoma Procedures
arm group type: Experimental
description: The following ocular procedures will fall under this arm of the study:
Ahmed valve
Ahmed valve with cataracts
Trabeculectomy
Trabeculectomy with cataracts
Baerveldt
Baerveldt with cataracts
Endocyclophotocoagulation
Endocyclophotocoagulation with cataracts
Istent
Cataracts with istent
Kahook
Cataracts with kahook
Cypass
Cypass with cataracts
Each subject will receive a capsule and an intravenous injection; however, they will not know which one is administering the sedation. Each patient will be randomized to one of the two groups listed below within this arm of the study:
Triazolam oral sedation with sodium chloride 0.9% intravenous placebo
Microcrystalline cellulose oral placebo with midazolam intravenous sedation
intervention type: Drug
intervention name: Triazolam
description: This will be used for oral sedation. This capsule or a microcrystalline cellulose placebo capsule will be administered depending on the randomized treatment group.
Dose for BMI less than 35: 0.125 mg
Dose for BMI greater than or equal to 35: 0.25 mg
arm group label: Cataract Procedures
arm group label: Cornea Procedures
arm group label: Glaucoma Procedures
arm group label: Retina Procedures
other name: Halcion
intervention type: Drug
intervention name: Midazolam
description: This will be used for intravenous sedation. This injection or sodium chloride 0.9% will be administered depending on the randomized treatment group.
Dose for BMI less than 35: 1.0 mg
Dose for BMI greater than or equal to 35: 2.0 mg
arm group label: Cataract Procedures
arm group label: Cornea Procedures
arm group label: Glaucoma Procedures
arm group label: Retina Procedures
other name: Versed
intervention type: Drug
intervention name: Microcrystalline Cellulose
description: This will be used for the oral placebo. This capsule or a triazolam capsule will be administered depending on the randomized treatment group.
Dose for BMI less than 35: 1 capsule
Dose for BMI greater than or equal to 35: 2 capsule
arm group label: Cataract Procedures
arm group label: Cornea Procedures
arm group label: Glaucoma Procedures
arm group label: Retina Procedures
other name: Avicel
intervention type: Drug
intervention name: Sodium chloride 0.9%
description: This will be used for the intravenous placebo.This injection or midazolam will be administered depending on the randomized treatment group.
Dose for BMI less than 35: volume to match volume of active intravenous medication
Dose for BMI greater than or equal to 35: volume to match volume of active intravenous medication
arm group label: Cataract Procedures
arm group label: Cornea Procedures
arm group label: Glaucoma Procedures
arm group label: Retina Procedures
other name: Normal Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Manju Subramanian, MD
role: Principal Investigator
affiliation: Boston Medical Center
facility: 
country: United States
url: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=575d8bf0-7af7-427c-a231-966e2a5e070d
description: Midazolam Drug Label Information
url: http://www.advancingsurgicalcare.com/reducinghealthcarecosts/costsavings/healthcarebluebookstudy
description: Commercial Insurance Costs Savings in Ambulatory Surgery Center 2016
citation: Ianchulev T, Litoff D, Ellinger D, Stiverson K, Packer M. Office-Based Cataract Surgery: Population Health Outcomes Study of More than 21 000 Cases in the United States. Ophthalmology. 2016 Apr;123(4):723-8. doi: 10.1016/j.ophtha.2015.12.020. Epub 2016 Jan 22.
PMID: 26804760
citation: American Society of Anesthesiologists Committee. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures: an updated report by the American Society of Anesthesiologists Committee on Standards and Practice Parameters. Anesthesiology. 2011 Mar;114(3):495-511. doi: 10.1097/ALN.0b013e3181fcbfd9. No abstract available.
PMID: 21307770
citation: Campbell J. Intravenous cannulation: potential complications. Prof Nurse. 1997 May;12(8 Suppl):S10-3.
PMID: 9180592
citation: Committee on Standards and Practice Parameters; Apfelbaum JL, Connis RT, Nickinovich DG; American Society of Anesthesiologists Task Force on Preanesthesia Evaluation; Pasternak LR, Arens JF, Caplan RA, Connis RT, Fleisher LA, Flowerdew R, Gold BS, Mayhew JF, Nickinovich DG, Rice LJ, Roizen MF, Twersky RS. Practice advisory for preanesthesia evaluation: an updated report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. Anesthesiology. 2012 Mar;116(3):522-38. doi: 10.1097/ALN.0b013e31823c1067. No abstract available.
PMID: 22273990
citation: Fung D, Cohen M, Stewart S, Davies A. Can the Iowa Satisfaction with Anesthesia Scale be used to measure patient satisfaction with cataract care under topical local anesthesia and monitored sedation at a community hospital? Anesth Analg. 2005 Jun;100(6):1637-1643. doi: 10.1213/01.ANE.0000154203.00434.23.
PMID: 15920188
citation: Erdurmus M, Aydin B, Usta B, Yagci R, Gozdemir M, Totan Y. Patient comfort and surgeon satisfaction during cataract surgery using topical anesthesia with or without dexmedetomidine sedation. Eur J Ophthalmol. 2008 May-Jun;18(3):361-7. doi: 10.1177/112067210801800308.
PMID: 18465717
responsible party type: Sponsor
mesh term: Midazolam
mesh term: Triazolam
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 