Surgery, Sedation
Conditions
Keywords
Ocular surgery, Intravenous sedation, Oral sedation
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.
Interventions
DRUGTriazolam
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
DRUGMidazolam
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
DRUGMicrocrystalline 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
DRUGSodium 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
Sponsors
Boston Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
TRIPLE (Subject, Caregiver, 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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Satisfaction | The patient satisfaction survey was administered up to two days after surgery. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Surgeon Satisfaction | The surgeon satisfaction survey will be administered immediately after the completion of the surgery. . | 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. |
| Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction | The anesthesiologist/CRNA satisfaction survey will be administered immediately after the completion of the surgical case. | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Requiring Additional Anesthesia Intervention | Information regarding additional anesthesia intervention will be collected within 2 days of completion of the subjects surgical procedure. | The number of subjects in each arm that received additional anesthetic agents during the operative procedure after the initial sedation. |
| Surgical Complication Rates | Information regarding surgical complications will be collected within 2 days of completion of the subjects surgical procedure. | The number of subjects in each arm that experienced a complication during the operative procedure after the initial sedation. |
Countries
United States
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.
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.
Participants by arm
| Arm | Count |
|---|---|
| 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
Triazolam or microcrystalline cellulose 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
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 | 85 |
| 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
Triazolam or microcrystalline cellulose 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
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 | 84 |
| Cornea Procedures The following ocular procedures will fall under this arm of the study:
* Descemet Stripping Endothelial Keratoplasty (DSEK)
* Cataracts with DSEK
* Descemet Membrane Endothelial Keratoplasty(DMEK)
* Cataracts with 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
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
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 | 70 |
| 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 (ECP)
* ECP 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% IV placebo
* Microcrystalline cellulose oral placebo with midazolam intravenous sedation
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
Midazolam or placebo: Given 5 minutes prior to surgery Dose for BMI less than 35: 1. | 44 |
| Total | 283 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Ineligible on day of surgery | 7 | 2 | 0 | 3 |
| Overall Study | Re-consented to participate | 0 | 0 | 0 | 1 |
| Overall Study | Study completed before surgical date | 2 | 1 | 8 | 1 |
| Overall Study | Transferred to other arm | 0 | 0 | 1 | 0 |
| Overall Study | Unable to obtain medication timely | 0 | 2 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 2 | 4 | 2 |
Baseline characteristics
| Characteristic | Cataract Procedures | Total | Glaucoma Procedures | Cornea Procedures | Retina Procedures |
|---|---|---|---|---|---|
| Age, Continuous | 64.59 years STANDARD_DEVIATION 9.14 | 59.67 years STANDARD_DEVIATION 13.96 | 66.52 years STANDARD_DEVIATION 11.32 | 49.96 years STANDARD_DEVIATION 14.99 | 57.02 years STANDARD_DEVIATION 12.65 |
| Body Mass Index (BMI) | 31.12 kg/m^2 STANDARD_DEVIATION 6.44 | 29.77 kg/m^2 STANDARD_DEVIATION 5.94 | 29.6 kg/m^2 STANDARD_DEVIATION 5.94 | 29.91 kg/m^2 STANDARD_DEVIATION 5.48 | 29.86 kg/m^2 STANDARD_DEVIATION 6.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 98 Participants | 8 Participants | 42 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 176 Participants | 32 Participants | 26 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 9 Participants | 4 Participants | 2 Participants | 3 Participants |
| Language English | 51 Participants | 158 Participants | 26 Participants | 25 Participants | 56 Participants |
| Language Haitian Creole | 8 Participants | 28 Participants | 9 Participants | 3 Participants | 8 Participants |
| Language Spanish | 26 Participants | 97 Participants | 9 Participants | 42 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants | 109 Participants | 28 Participants | 19 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 29 Participants | 112 Participants | 13 Participants | 41 Participants | 29 Participants |
| Race (NIH/OMB) White | 22 Participants | 58 Participants | 2 Participants | 9 Participants | 25 Participants |
| Sex: Female, Male Female | 43 Participants | 124 Participants | 20 Participants | 23 Participants | 38 Participants |
| Sex: Female, Male Male | 42 Participants | 159 Participants | 24 Participants | 47 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 85 | 0 / 84 | 0 / 70 | 0 / 44 |
| other Total, other adverse events | 8 / 85 | 17 / 84 | 6 / 70 | 6 / 44 |
| serious Total, serious adverse events | 1 / 85 | 0 / 84 | 0 / 70 | 0 / 44 |
Outcome results
Primary
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.
Time frame: The patient satisfaction survey was administered up to two days after surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cataract Procedures | Patient Satisfaction | 5.37 score on a scale | Standard Deviation 0.57 |
| Retina Procedures | Patient Satisfaction | 5.23 score on a scale | Standard Deviation 0.72 |
| Cornea Procedures | Patient Satisfaction | 5.37 score on a scale | Standard Deviation 0.68 |
| Glaucoma Procedures | Patient Satisfaction | 5.05 score on a scale | Standard Deviation 0.87 |
Comparison: 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.~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.p-value: <0.05ANCOVA
Secondary
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.
Time frame: The anesthesiologist/CRNA satisfaction survey will be administered immediately after the completion of the surgical case.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cataract Procedures | Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction | 5.16 score on a scale | Standard Deviation 0.96 |
| Retina Procedures | Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction | 5.14 score on a scale | Standard Deviation 0.94 |
| Cornea Procedures | Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction | 5.33 score on a scale | Standard Deviation 0.81 |
| Glaucoma Procedures | Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction | 4.9 score on a scale | Standard Deviation 0.96 |
Comparison: 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.~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.p-value: <0.05ANCOVA
Secondary
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.
Time frame: The surgeon satisfaction survey will be administered immediately after the completion of the surgery. .
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cataract Procedures | Surgeon Satisfaction | 5.28 score on a scale | Standard Deviation 0.97 |
| Retina Procedures | Surgeon Satisfaction | 5.57 score on a scale | Standard Deviation 0.84 |
| Cornea Procedures | Surgeon Satisfaction | 5.34 score on a scale | Standard Deviation 0.95 |
| Glaucoma Procedures | Surgeon Satisfaction | 4.6 score on a scale | Standard Deviation 1.37 |
Comparison: 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.~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.p-value: <0.05ANCOVA
Other Pre-specified
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.
Time frame: Information regarding additional anesthesia intervention will be collected within 2 days of completion of the subjects surgical procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cataract Procedures | Number of Participants Requiring Additional Anesthesia Intervention | 11 Participants |
| Retina Procedures | Number of Participants Requiring Additional Anesthesia Intervention | 8 Participants |
| Cornea Procedures | Number of Participants Requiring Additional Anesthesia Intervention | 11 Participants |
| Glaucoma Procedures | Number of Participants Requiring Additional Anesthesia Intervention | 16 Participants |
Comparison: 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.~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 proceduresp-value: <0.05t-test, 2 sided
Other Pre-specified
Surgical Complication Rates
The number of subjects in each arm that experienced a complication during the operative procedure after the initial sedation.
Time frame: Information regarding surgical complications will be collected within 2 days of completion of the subjects surgical procedure.
Population: Data was not available for one participant in the cornea arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cataract Procedures | Surgical Complication Rates | 11 Participants |
| Retina Procedures | Surgical Complication Rates | 8 Participants |
| Cornea Procedures | Surgical Complication Rates | 1 Participants |
| Glaucoma Procedures | Surgical Complication Rates | 6 Participants |
Comparison: 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.~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.p-value: <0.05t-test, 2 sided