Oral Versus Intravenous Sedation for Ocular Procedures

Study Overview
=================
Brief Summary
-----------------
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).

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.

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

Conditions
-----------------
Surgery, Sedation

Intervention / Treatment
-----------------
* Drug: Triazolam
* Drug: Midazolam
* Drug: Microcrystalline Cellulose
* Drug: Sodium chloride 0.9%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years or older Ability to speak and read in English or Spanish or Haitian Creole Subjects able to consent for themselves 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: Surgical plan which includes general anesthesia Hypersensitivity or allergy to benzodiazepines Women who are pregnant, have a positive pregnancy test on the day of surgery, refuse a pregnancy test, or are nursing Previous delirium after anesthesia with a benzodiazepine Subjects 70 years of age or older who fail the delirium pre-screening questionnaire as shown in Appendix Section 15.6 Currently experiencing the effects of drug/alcohol Current oral/IV regimen of any medication inhibiting cytochrome P450 3A which includes ketoconazole, itraconazole, nefazodone, ritonavir, indinavir, nelavir, saquinavir, and lopinavir Subjects already enrolled in this study for the fellow eye Subjects enrolled in a clinical trial with an investigational drug within the past 3 months Failed anesthesia clearance to receive a benzodiazepine

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cataract Procedures<br>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<br>* 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<br>* Other names: Halcion;Drug: Midazolam<br>* 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<br>* Other names: Versed;Drug: Microcrystalline Cellulose<br>* 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<br>* Other names: Avicel;Drug: Sodium chloride 0.9%<br>* 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<br>* Other names: Normal Saline;|
| Experimental: Retina Procedures<br>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<br>* 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<br>* Other names: Halcion;Drug: Midazolam<br>* 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<br>* Other names: Versed;Drug: Microcrystalline Cellulose<br>* 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<br>* Other names: Avicel;Drug: Sodium chloride 0.9%<br>* 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<br>* Other names: Normal Saline;|
| Experimental: Cornea Procedures<br>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<br>* 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<br>* Other names: Halcion;Drug: Midazolam<br>* 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<br>* Other names: Versed;Drug: Microcrystalline Cellulose<br>* 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<br>* Other names: Avicel;Drug: Sodium chloride 0.9%<br>* 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<br>* Other names: Normal Saline;|
| Experimental: Glaucoma Procedures<br>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<br>* 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<br>* Other names: Halcion;Drug: Midazolam<br>* 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<br>* Other names: Versed;Drug: Microcrystalline Cellulose<br>* 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<br>* Other names: Avicel;Drug: Sodium chloride 0.9%<br>* 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<br>* 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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ocular surgery, Intravenous sedation, Oral sedation