Oral Versus Intravenous Sedation for Ocular Procedures

A Single-center, Randomized, Double-blind, Double-dummy, Parallel-group Study Comparing Oral Sedation to Intravenous Sedation for Ocular Procedures.

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).

Study Overview

• Status: Completed
• Conditions: Surgery; Sedation
• Intervention / Treatment: Drug: Triazolam; Drug: Midazolam; Drug: Microcrystalline Cellulose; Drug: Sodium chloride 0.9%

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 327
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 years or older
2. Ability to speak and read in English or Spanish or Haitian Creole
3. Subjects able to consent for themselves

4. Outpatient surgical plan for any of the following procedures:

   • Cataract surgery: cataracts
   • Retina: pars plana vitrectomy, pars plana vitrectomy with cataracts, epiretinal membrane peel, pars plana lensectomy, and/or endolaser, silicone oil removal
   • Cornea: descemet stripping endothelial keratopathy, cataracts with descemet stripping endothelial keratopathy, descemet membrane endothelial keratoplasty, cataracts with descemet membrane endothelial keratoplasty, conjunctival and/or corneal lesion excisions, pterygium
   • Glaucoma: ahmed valve, ahmed valve with cataracts,trabeculectomy, trabeculectomy with cataracts, baerveldt, baerveldt with cataracts, endocyclophotocoagulation, endocyclophotocoagulation with cataracts, istent, istent with cataracts, kahook, kahook with cataracts, cypass, cypass with cataracts

Exclusion Criteria:

1. Surgical plan which includes general anesthesia
2. Hypersensitivity or allergy to benzodiazepines
3. Women who are pregnant, have a positive pregnancy test on the day of surgery, refuse a pregnancy test, or are nursing
4. Previous delirium after anesthesia with a benzodiazepine
5. Subjects 70 years of age or older who fail the delirium pre-screening questionnaire as shown in Appendix Section 15.6
6. Currently experiencing the effects of drug/alcohol
7. Current oral/IV regimen of any medication inhibiting cytochrome P450 3A which includes ketoconazole, itraconazole, nefazodone, ritonavir, indinavir, nelavir, saquinavir, and lopinavir
8. Subjects already enrolled in this study for the fellow eye
9. Subjects enrolled in a clinical trial with an investigational drug within the past 3 months
10. Failed anesthesia clearance to receive a benzodiazepine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cataract Procedures; 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	Drug: Triazolam; 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; Other Names: Halcion; Drug: Midazolam; 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; Other Names: Versed; Drug: Microcrystalline Cellulose; 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; Other Names: Avicel; Drug: Sodium chloride 0.9%; 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; Other Names: Normal Saline
Experimental: Retina Procedures; 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	Drug: Triazolam; 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; Other Names: Halcion; Drug: Midazolam; 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; Other Names: Versed; Drug: Microcrystalline Cellulose; 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; Other Names: Avicel; Drug: Sodium chloride 0.9%; 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; Other Names: Normal Saline
Experimental: Cornea Procedures; 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	Drug: Triazolam; 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; Other Names: Halcion; Drug: Midazolam; 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; Other Names: Versed; Drug: Microcrystalline Cellulose; 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; Other Names: Avicel; Drug: Sodium chloride 0.9%; 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; Other Names: Normal Saline
Experimental: Glaucoma Procedures; 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	Drug: Triazolam; 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; Other Names: Halcion; Drug: Midazolam; 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; Other Names: Versed; Drug: Microcrystalline Cellulose; 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; Other Names: Avicel; Drug: Sodium chloride 0.9%; 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; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Satisfaction	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.	The patient satisfaction survey was administered up to two days after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgeon Satisfaction	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.	The surgeon satisfaction survey will be administered immediately after the completion of the surgery. .
Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction	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.	The anesthesiologist/CRNA satisfaction survey will be administered immediately after the completion of the surgical case.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Requiring Additional Anesthesia Intervention	The number of subjects in each arm that received additional anesthetic agents during the operative procedure after the initial sedation.	Information regarding additional anesthesia intervention will be collected within 2 days of completion of the subjects surgical procedure.
Surgical Complication Rates	The number of subjects in each arm that experienced a complication during the operative procedure after the initial sedation.	Information regarding surgical complications will be collected within 2 days of completion of the subjects surgical procedure.

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Investigators: Principal Investigator: Manju Subramanian, MD, Boston Medical Center

Publications and helpful links

General Publications

• 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.
• 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.
• Campbell J. Intravenous cannulation: potential complications. Prof Nurse. 1997 May;12(8 Suppl):S10-3.
• 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.
• 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.
• 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.

Helpful Links

• Midazolam Drug Label Information
• Commercial Insurance Costs Savings in Ambulatory Surgery Center 2016

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2017
• Primary Completion (Actual): November 30, 2019
• Study Completion (Actual): November 30, 2019

Study Registration Dates

• First Submitted: August 2, 2017
• First Submitted That Met QC Criteria: August 8, 2017
• First Posted (Actual): August 11, 2017

Study Record Updates

• Last Update Posted (Actual): August 19, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Intravenous sedation; Ocular surgery; Oral sedation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam; Triazolam
• Other Study ID Numbers: H-36590

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes