A Randomized, Double-Masked, Controlled, Single Site Investigator Initiated, Exploratory Study of the Midazolam/Ketamine Melt vs Ketamine Melt Alone vs Midazolam Melt Alone in Subjects Undergoing Intraocular Surgery.

Study Overview
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Brief Summary
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This study is designed to explore the sedative and analgesic effectiveness of the Midazolam/Ketamine melt compared to Midazolam melt alone or Ketamine melt alone in subjects undergoing intraocular surgery.

Detailed Description
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Cataract surgery today is a highly effective and efficient procedure, with average times for completion ranging around 15 minutes in duration. Patients undergoing cataract surgery are typically given sedatives and often times pain medication (e.g. opioids) just prior to and during the procedure. The overwhelming majority of patients are given these medications via intravenous administration. The insertion of an IV line has been associated with patient complaints of pain and bruising, and can increase the administrative burden on the clinical staff. In addition to the national crisis surrounding opioid abuse, opioids have many negative side effects during cataract surgery such as respiratory depression, dizziness, nausea, and post- operative vomiting. To reduce the side effects, improve patient satisfaction, and help surgical center flow the Midazolam/Ketamine melt (MK Melt) has been suggested as an alternative to provide sedation and analgesia in subjects undergoing minor outpatient surgery, such as cataract surgery. The addition of ketamine should provide enough analgesia for the mild discomfort reported during cataract surgery. This study is intended to evaluate the MK Melt and its ability to provide an adequate level of both sedation and intraoperative pain control vs an active control.

Official Title
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A Randomized, Double-Masked, Controlled, Single Site Investigator Initiated, Exploratory Study of the Midazolam/Ketamine Melt vs Ketamine Melt Alone vs Midazolam Melt Alone in Subjects Undergoing Intraocular Surgery.

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: Midazolam/Ketamine HCl 3mg-50mg sublingual
* Drug: Midazolam 3mg Sublingual
* Drug: Ketamine 50mg Sublingual


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be male or female, and between the ages of 55-80 years old. Subjects willing and able to sign the informed consent and capable of committing to the duration of the study. Subjects undergoing uncomplicated stand-alone cataract surgery without planned use of Omidria or intra-operative lidocaine. Subjects that are willing to have an IV placed prior to intraocular surgery Subjects undergoing first eye cataract surgery Subjects that in the opinion of the investigator can tolerate 1 dose of MK 3/50 Melt. Exclusion Criteria: Subjects who have undergone sedation in the past 90 days. Women who are pregnant or lactating at the time of the study. Subjects who do not wish to or cannot comply with study procedures. Subject with any cognitive impairment (i.e: Alzheimer's, dementia, etc.) that in the opinion of the investigator may confound the study results. Subjects with history of substance abuse. Subjects that are currently taking a prescription pain medication. Subjects that are not willing to abstain from all over-the-counter pain medication with the exception of 500-1000mg acetaminophen for 24 hours prior to surgery. Subjects that are not willing to abstain from NSAID or steroid eye drops prior to surgery. Subjects with planned use of femtosecond laser, zepto, iris hooks or a malyugin ring during cataract surgery. Subjects with chronic pain rated moderate to severe within the past week. Subjects that have a psychiatric disorder that is currently uncontrolled. Subjects scheduled for same day bilateral or second eye cataract surgery.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1:1 treatment arms. Arm 1 Ketamine/Midazolam melt. Arm 2 Ketamine melt. Arm 3 Midazolam melt.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midazolam/Ketamine Melt<br>One Midazolam/Ketamine 3mg/50mg melt administered sublingually | Drug: Midazolam/Ketamine HCl 3mg-50mg sublingual<br>* Single sublingual administration of Midazolam/Ketamine HCl 3mg-50mg sublingually prior to surgery<br>|
| Active Comparator: Midazolam Melt<br>Midazolam 3mg melt administered sublingually | Drug: Midazolam 3mg Sublingual<br>* Single sublingual administration of Midazolam 3mg sublingually prior to surgery<br>|
| Active Comparator: Ketamine Melt<br>Ketamine 50mg melt administered sublingually | Drug: Ketamine 50mg Sublingual<br>* Single sublingual administration of Ketamine HCl 50mg sublingually prior to surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Sedation | The Doctor/Nurse Anesthetist will evaluate the subject's level of sedation on the Ramsey Sedation Scale. Adequate sedation demonstrated by a score of 2 or higher on the Ramsey Scale: Upon entering operative room (before being prepped and draped) Immediately post-op upon entering the PACU The Ramsey scale is: Patient is anxious and agitated or restless, or both Patient is co-operative, oriented, and tranquil Patient responds to commands only Patient exhibits brisk response to light glabellar tap or loud auditory stimulus Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus Patient exhibits no response Source: Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxolone-alphadalone. BMJ. 1974;2:656-659. | Duration of surgery | 
| Level of Pain | Adequate pain control demonstrated by a score of 3 or below on the Numeric Pain Rating Scale (NPRS) by asking the following questions at the following times: How painful was that on a scale of 0=no pain to 10=extreme pain? will be asked: Upon insertion of the speculum Upon first incision Upon insertion of phacoemulsification probe Upon Lens insertion Upon removal of sterile drape How would you rate your worst pain during surgery on a scale of 0=no pain to 10=extreme pain? will be asked: Immediately after surgery in the OR 10-15 mins after the subject reaches the PACU On a scale of 0=no pain to 10=extreme pain what number best describes your overall pain during the surgery? Will be asked: Immediately after surgery in the OR 10-15 mins after the subject reaches the PACU | Duration of surgery | 
| Need for Rescue Medication | Percentage of patients requiring rescue medication (IV Fentanyl) for pain. Rescue medication will only be giving if a subject reports a pain level of 4 or higher on the NPRS. | Duration of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eye Movement During Surgery | Eye movement during surgery (evaluated by a masked evaluator by reviewing operative recording). | Duration of surgery | 
| Clinician's Global Impression | Clinician's impression of patient's sedation during surgery | Duration of surgery | 
| Patient Satisfaction | Patient satisfactions, determined by asking the patient How satisfied were you with your overall experience? at the one-day post-op or via phone call one-day post-op. | 1 day post operatively |