PhacoemulsificationPhase 4NCT03054103
Sedation Methods During Cataract Surgery
A Phase 4 study testing Midazolam + Ketamine 10 MG/ML: 0.5 ML, Midazolam + Ketamine 10 MG/ML: 1 ML and Midazolam + Normal saline in people with Phacoemulsification and Cataract, run by Wake Forest University Health Sciences.
Trial summary
Background: Phacoemulsification is the most common surgical procedure performed in the United States and European Union and sedation is commonly used during phacoemulsification to help alleviate patient anxiety and prevent the patient from interfering with the procedure. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Phacoemulsification, Cataract
- What is being tested?
- Midazolam + Ketamine 10 MG/ML: 0.5 ML, Midazolam + Ketamine 10 MG/ML: 1 ML and Midazolam + Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- No sites listed yet
- Study dates
- 3 May 2016to 11 Nov 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients met inclusion criteria if they were between 18- and 80-years-old and undergoing elective cataract surgery performed by a single ophthalmologist (KW).
Who cannot join
- Patients younger than 18, older than 80, those with a serum creatinine >3 mg/dl, advanced liver disease (liver enzymes twice the normal range or higher), and those with an allergy to any of the study medications were excluded from the study.
About this study
Official title: A Comparison of Midazolam vs. Midazolam/Ketamine for Conscious Sedation in Patients Undergoing Phacoemulsification Under Topical Anesthesia
Background: Phacoemulsification is the most common surgical procedure performed in the United States and European Union and sedation is commonly used during phacoemulsification to help alleviate patient anxiety and prevent the patient from interfering with the procedure. The investigators have administered ketamine in addition to midazolam in this regard. To study the effectiveness of this technique, The investigators proposed a study to determine if adding low-dose ketamine to midazolam has any beneficial (or negative) effects on operating conditions, patient satisfaction, and recovery during and after unilateral phacoemulsification procedures performed using topical anesthesia and intravenous (IV) conscious sedation.
Methods: In a free-standing Outpatient Surgery Center, the investigators conducted a randomized, double-masked, 3-arm, prospective comparison of IV midazolam only vs. midazolam with ketamine 5 mg IV vs. midazolam with ketamine 10 mg IV. The investigators then measured a single surgeon's assessment of surgical conditions, self-reported patient satisfaction, postoperative pain score, and duration of postoperative stay. The investigators also analyzed the dose of midazolam required to meet subjective anxiolysis in each group.
Read the detailed description
Phacoemulsification is the most common surgical procedure performed in the United States and European Union. In addition, the number of diagnoses of cataracts is expected to double from 25,000,000 in 2010 to 50,000,000 in 2050 while the incidence of phacoemulsification is also increasing. Therefore, any attempt to optimize outcome and efficiency is significant.
Sedation is commonly used during phacoemulsification to help alleviate patient anxiety and prevent the patient from interfering with the procedure. However, a great deal of variation exists in anesthetic management of these cases. Investigators have published use of a number of agents for sedation in the literature. These include midazolam, clonidine, propofol, fentanyl, dexmedetomidine, remifentanil, and oral diazepam. Intravenous (IV) clonidine has a half-life of 9-13 h and increased risk of postoperative hypotension. Propofol causes disinhibition and it has to be titrated during surgery to prevent oversedation. Opioids carry an increased risk of respiratory depression, prolonged sedation, as well as delirium in the elderly. Finally, oral medications do not allow for quick dose adjustments during surgery.
Intravenous midazolam is commonly used for sedation during phacoemulsification and other minor procedures. It has properties as an anxiolytic, muscle relaxant, and it is effective at reducing intraocular pressure. However, anxious patients administered benzodiazepines may require higher doses during cataract surgery which can lead to oversedation or disinhibition with subsequent patient movement. These responses can reduce the patient's ability to follow simple commands which can affect surgical outcome. Additionally, patients who receive too much sedation may fall asleep and wake up startled, similarly compromising the outcome of the surgery.
In the search for additional medications that can improve surgical conditions and patient comfort during phacoemulsification, the investigators explored the use of a medication that can improve analgesia and reduce patient movement during procedures, namely ketamine. Ketamine is an NMDA antagonist with both sedative and analgesic properties and has minimal effects on respiration. Ketamine has been used to premedicate and sedate patients undergoing day care procedures without adverse effects, and patients, typically, remain cooperative albeit being sedated. These properties along with its relatively short elimination half-life of 2 h (compared with 3-4 h for midazolam) make ketamine an attractive agent for sedation during monitored anesthesia care (MAC) for cataract surgery.
The purpose of this study was to determine if adding low-dose ketamine to midazolam has any beneficial (or negative) effects on operating conditions, patient satisfaction, and recovery during and after unilateral phacoemulsification procedures performed using topical anesthesia and IV conscious sedation.
The investigators measured the surgeon's assessment of the participant's cooperation during surgery according to a predetermined Likert scale. The investigators also recorded the following outcome measures regarding each participant's surgery: 1) total dose of midazolam, 2) average time spent in the procedural room, 3) postoperative length of stay (LOS), and 4) average postoperative pain score. The subjects received a survey inquiring about the subjects' comfort and sedation level during surgery. Finally, the investigators recorded the following demographic data for all participants: gender, age, psychiatric diagnoses, and use of CNS, psychiatric, or opioid medications.
Statistical Analysis The investigators used Fisher's exact test for examining data expressed as percentages, and Students t-test for yes/no data, and repeated measures ANOVA for 3 group analysis (LOS, surgical duration). The investigators judged significance at a P-value of 0.05. The investigators utilized a generalized estimated equations (GEE) to fit a logistic model to assess differences in the responses of patients based on amount of ketamine received. The GEE approach can fit models to correlated outcomes, as in the case where subjects had more than one procedure performed.
- Conditions
- Phacoemulsification, Cataract
- Being tested
- Midazolam + Ketamine 10 MG/ML: 0.5 ML, Midazolam + Ketamine 10 MG/ML: 1 ML, Midazolam + Normal saline
- Keywords
- ketamine, midazolam, sedation
- Medical subject headings
- Cataract
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Midazolam + Ketamine 10 MG/ML: 0.5 MLDrug
Also called Ketalar
5 mg ketamine IV given just prior to onset of case. Then titrated midazolam up to 2 mg IV at beginning and during case.
Midazolam + Ketamine 10 MG/ML: 1 MLDrug
Also called Ketalar
10 mg ketamine IV given just prior to onset of case. Then titrated midazolam up to 2 mg IV at beginning and during case.
Midazolam + Normal salineDrug
Also called NS
Preoperative control: Normal saline placebo given preoperatively. Then protocol followed for titration of midazolam up to 2 mg IV at beginning and during case.
| Study group | Role | What they receive |
|---|---|---|
| Midazolam alone | Placebo comparator | Drug: Midazolam titrated 0.5-2.0 mg + normal saline placebo. Midazolam + Normal saline Receives: Drug: Midazolam + Normal saline |
| Midazolam + Ketamine 5 mg | Active comparator | Drug: Midazolam titrated 0.5-2.0 mg + Ketamine 10 MG/ML: 0.5 ML. Midazolam + Ketamine 10 MG/ML: 0.5 ML Receives: Drug: Midazolam + Ketamine 10 MG/ML: 0.5 ML |
| Midazolam + Ketamine 10 mg | Active comparator | Drug: Midazolam titrated 0.5-2.0 mg + Ketamine 10 MG/ML: 1 ML. Midazolam + Ketamine 10 MG/ML: 1 ML Receives: Drug: Midazolam + Ketamine 10 MG/ML: 1 ML |
What is being measured
The primary outcome is the main question the study is designed to answer.
Eye Mobility During Surgery (See Link to Study Protocol for Scale)
Scale of mobility of eye during surgery rate 0 (no movement) to 3 (movement enough to stop surgery).
Measured: Intraoperative, end of operation reported
Secondary outcomes (3)
Measure of Comfort (See Link to Study Protocol for Scale)
Measure of comfort (0-3; 0=very comfortable to 3=extremely uncomfortable
Measured: Obtained on the first day after surgery during the subject's routine postoperative check in the Ophthalmology Clinic.
PACU Length of Stay
This is obtained from the records as time spent in the PACU (Recovery Room) after surgery.
Measured: This will occur one time only, in a range of 20 to 30 minutes after the surgery is completed.
Nausea
Self-reported incidence of nausea. This will be assessed by asking the subjects once (just prior to discharge from the PACU) whether they experienced any nausea while they were in the PACU (Recovery Room) and will be a measurement of the count of participants that experienced nausea during this period
Measured: This will occur from time of entry into PACU to time of departure after their surgery. (One time only, in a range of 20 to 30 minutes after surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2017
- Study start3 May 2016
- Primary completion5 Nov 2016
- Study completion11 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PhacoemulsificationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, controlled, double-masked, three-armed clinical comparison
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Timothy N Harwood, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03054103
- Sponsor's protocol ID
- IRB00031444
- Status last verified
- Aug 2018
- First submitted
- 2 Feb 2017
- Last updated
- 10 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparison of Midazolam vs. Midazolam/Ketamine for Conscious Sedation in Patients Undergoing Phacoemulsification Under Topical Anesthesia
- ClinicalTrials.gov ID
- NCT03054103
- Acronym / sponsor ID
- IRB00031444
- Conditions
- Phacoemulsification, Cataract
- Keywords
- ketamine, midazolam, sedation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- 3 May 2016 (actual)
- Primary completion
- 5 Nov 2016 (actual)
- Study completion
- 11 Nov 2016 (actual)
- First posted
- 15 Feb 2017 (actual)
- Results
- Posted 19 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Phacoemulsification is the most common surgical procedure performed in the United States and European Union and sedation is commonly used during phacoemulsification to help alleviate patient anxiety and prevent the patient from interfering with the procedure. The investigators have administered ketamine in addition to midazolam in this regard. To study the effectiveness of this technique, The investigators proposed a study to determine if adding low-dose ketamine to midazolam has any beneficial (or negative) effects on operating conditions, patient satisfaction, and recovery during and after unilateral phacoemulsification procedures performed using topical anesthesia and intravenous (IV) conscious sedation.
Methods: In a free-standing Outpatient Surgery Center, the investigators conducted a randomized, double-masked, 3-arm, prospective comparison of IV midazolam only vs. midazolam with ketamine 5 mg IV vs. midazolam with ketamine 10 mg IV. The investigators then measured a single surgeon's assessment of surgical conditions, self-reported patient satisfaction, postoperative pain score, and duration of postoperative stay. The investigators also analyzed the dose of midazolam required to meet subjective anxiolysis in each group.
Detailed description
Phacoemulsification is the most common surgical procedure performed in the United States and European Union. In addition, the number of diagnoses of cataracts is expected to double from 25,000,000 in 2010 to 50,000,000 in 2050 while the incidence of phacoemulsification is also increasing. Therefore, any attempt to optimize outcome and efficiency is significant.
Sedation is commonly used during phacoemulsification to help alleviate patient anxiety and prevent the patient from interfering with the procedure. However, a great deal of variation exists in anesthetic management of these cases. Investigators have published use of a number of agents for sedation in the literature. These include midazolam, clonidine, propofol, fentanyl, dexmedetomidine, remifentanil, and oral diazepam. Intravenous (IV) clonidine has a half-life of 9-13 h and increased risk of postoperative hypotension. Propofol causes disinhibition and it has to be titrated during surgery to prevent oversedation. Opioids carry an increased risk of respiratory depression, prolonged sedation, as well as delirium in the elderly. Finally, oral medications do not allow for quick dose adjustments during surgery.
Intravenous midazolam is commonly used for sedation during phacoemulsification and other minor procedures. It has properties as an anxiolytic, muscle relaxant, and it is effective at reducing intraocular pressure. However, anxious patients administered benzodiazepines may require higher doses during cataract surgery which can lead to oversedation or disinhibition with subsequent patient movement. These responses can reduce the patient's ability to follow simple commands which can affect surgical outcome. Additionally, patients who receive too much sedation may fall asleep and wake up startled, similarly compromising the outcome of the surgery.
In the search for additional medications that can improve surgical conditions and patient comfort during phacoemulsification, the investigators explored the use of a medication that can improve analgesia and reduce patient movement during procedures, namely ketamine. Ketamine is an NMDA antagonist with both sedative and analgesic properties and has minimal effects on respiration. Ketamine has been used to premedicate and sedate patients undergoing day care procedures without adverse effects, and patients, typically, remain cooperative albeit being sedated. These properties along with its relatively short elimination half-life of 2 h (compared with 3-4 h for midazolam) make ketamine an attractive agent for sedation during monitored anesthesia care (MAC) for cataract surgery.
The purpose of this study was to determine if adding low-dose ketamine to midazolam has any beneficial (or negative) effects on operating conditions, patient satisfaction, and recovery during and after unilateral phacoemulsification procedures performed using topical anesthesia and IV conscious sedation.
The investigators measured the surgeon's assessment of the participant's cooperation during surgery according to a predetermined Likert scale. The investigators also recorded the following outcome measures regarding each participant's surgery: 1) total dose of midazolam, 2) average time spent in the procedural room, 3) postoperative length of stay (LOS), and 4) average postoperative pain score. The subjects received a survey inquiring about the subjects' comfort and sedation level during surgery. Finally, the investigators recorded the following demographic data for all participants: gender, age, psychiatric diagnoses, and use of CNS, psychiatric, or opioid medications.
Statistical Analysis The investigators used Fisher's exact test for examining data expressed as percentages, and Students t-test for yes/no data, and repeated measures ANOVA for 3 group analysis (LOS, surgical duration). The investigators judged significance at a P-value of 0.05. The investigators utilized a generalized estimated equations (GEE) to fit a logistic model to assess differences in the responses of patients based on amount of ketamine received. The GEE approach can fit models to correlated outcomes, as in the case where subjects had more than one procedure performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
- Model description
- Randomized, controlled, double-masked, three-armed clinical comparison
| Arm | Type | Receives |
|---|---|---|
| Midazolam alone | Placebo comparator | Drug: Midazolam + Normal salineDrug: Midazolam titrated 0.5-2.0 mg + normal saline placebo. Midazolam + Normal saline |
| Midazolam + Ketamine 5 mg | Active comparator | Drug: Midazolam + Ketamine 10 MG/ML: 0.5 MLDrug: Midazolam titrated 0.5-2.0 mg + Ketamine 10 MG/ML: 0.5 ML. Midazolam + Ketamine 10 MG/ML: 0.5 ML |
| Midazolam + Ketamine 10 mg | Active comparator | Drug: Midazolam + Ketamine 10 MG/ML: 1 MLDrug: Midazolam titrated 0.5-2.0 mg + Ketamine 10 MG/ML: 1 ML. Midazolam + Ketamine 10 MG/ML: 1 ML |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients met inclusion criteria if they were between 18- and 80-years-old and undergoing elective cataract surgery performed by a single ophthalmologist (KW).
Key exclusion criteria (1 listed)
- Patients younger than 18, older than 80, those with a serum creatinine >3 mg/dl, advanced liver disease (liver enzymes twice the normal range or higher), and those with an allergy to any of the study medications were excluded from the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Midazolam + Ketamine 10 MG/ML: 0.5 MLAlso: Ketalar5 mg ketamine IV given just prior to onset of case. Then titrated midazolam up to 2 mg IV at beginning and during case. | Drug | Midazolam + Ketamine 5 mg |
| Midazolam + Ketamine 10 MG/ML: 1 MLAlso: Ketalar10 mg ketamine IV given just prior to onset of case. Then titrated midazolam up to 2 mg IV at beginning and during case. | Drug | Midazolam + Ketamine 10 mg |
| Midazolam + Normal salineAlso: NSPreoperative control: Normal saline placebo given preoperatively. Then protocol followed for titration of midazolam up to 2 mg IV at beginning and during case. | Drug | Midazolam alone |
Primary outcome
Eye Mobility During Surgery (See Link to Study Protocol for Scale)
Time frame: Intraoperative, end of operation reported
Scale of mobility of eye during surgery rate 0 (no movement) to 3 (movement enough to stop surgery).
3 secondary outcomes
Measure of Comfort (See Link to Study Protocol for Scale)
Time frame: Obtained on the first day after surgery during the subject's routine postoperative check in the Ophthalmology Clinic.
PACU Length of Stay
Time frame: This will occur one time only, in a range of 20 to 30 minutes after the surgery is completed.
Nausea
Time frame: This will occur from time of entry into PACU to time of departure after their surgery. (One time only, in a range of 20 to 30 minutes after surgery.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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"Comparative Study of High-frequency Pulsed Vacuum Technology Versus Phacoemulsification for Cataract Surgery
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A Phase 3 Study Evaluating the Safety and Efficacy of TRIESENCE® (Injectable Suspension) for the Treatment of Ocular Inflammation and Pain After Ophthalmic Surgery
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Combined Phacoemulsification-Goniotomy in Primary Open-Angle and Primary Angle-Closure Glaucoma
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy N Harwood, MD principal investigator
Wake Forest University Health Sciences
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Midazolam + Ketamine 10 MG/ML: 0.5 ML, Midazolam + Ketamine 10 MG/ML: 1 ML and Midazolam + Normal saline in people with Phacoemulsification and Cataract, run by Wake Forest University Health Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Eye Mobility During Surgery (See Link to Study Protocol for Scale) (time frame: Intraoperative, end of operation reported). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2018.