Efficacy of Propofol or Midazolam Compare to Placebo for Preoperative Medication

February 17, 2016 updated by: Ronald Wender, Cedars-Sinai Medical Center

Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Propofol or Midazolam Versus Placebo for Preoperative Medication in Patients Undergoing Elective Orthopedic Surgery

The purpose of this research is:

To evaluate the sedative (reduces irritability or agitation), anxiolytic (reduces anxiety), and amnesic (produces temporary lack of recall) effects of propofol or midazolam when administered for preoperative medication (before administration of drugs that will put patient to sleep) in comparison to placebo. This study is to test whether the use of the pre-anesthesia medication measurably reduces anxiety in comparison to receiving no pre-anesthesia medication prior to orthopedic procedures.

To assess the effect of propofol in comparison to placebo and midazolam on the ability to recall (memory of):

  • when the doctor places the mask on patient's face prior to going to sleep
  • recall of 2 pictures
  • on your satisfaction with the anesthesia as well as postoperative side effects in post-anesthesia care unit (PACU) e.g., nausea ,vomiting and sedation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The role of anxiolytic premedication in the ambulatory surgical population is frequently debated. Anesthesiologists may consider the administration of anxiety-reducing drugs unnecessary when anxiety levels are low in outpatients presenting for minor surgery. However, the previous study reports that up to 80% of outpatients expressed a preference for a combination of anxiety-reducing and hypnotic premedication before surgery (1-4). In addition to anxiolysis, goals of anxiolytic premedication include sedation, amnesia, improved patient cooperation, and/or improved patient satisfaction. Intravenous (IV) midazolam is the most commonly used premedicant in the ambulatory setting due to its rapid onset, and short half-life (2,3,5), but its residual effects in the immediate postoperative period may contribute to postoperative sedation, as well as to delayed recovery and discharge-readiness after brief outpatient surgery. Furthermore, White et al. (6) noted that the slope of the dose-response curve for sedation was much steeper with midazolam compared with diazepam, which suggests that midazolam may possess a smaller margin of safety and greater need for careful titration to achieve the desired clinical end-point without untoward side effects.

Propofol has become the IV (intravenous) anesthetic of choice for ambulatory anesthesia because of its excellent recovery profile (7). Clinical experience with propofol in the ambulatory setting suggests that its use is associated with less residual sedation and lower incidence of postoperative nausea and vomiting (PONV) (8). However, there are some undesirable side effects associated with propofol including pain on injection, cardiovascular and respiratory depression, and occasional excitement on emergence from anesthesia (9). Practically, small doses of propofol (10-20 mg IV) have been used as an anxiolytic/sedative medication.

To date, there is only one study that has evaluated propofol versus midazolam versus placebo as premedication (10). In this study, the authors stated that propofol (0.4 mg/kg IV) had anxiolytic effects comparable in magnitude and duration to midazolam (0.04 mg/kg IV) with less memory impairment, respiratory depression and dizziness. However, they did not assess the efficacy of propofol and midazolam as a premedication on the recovery profiles and patient's satisfaction in their study. Compared to placebo and propofol, midazolam was associated with more frequent respiratory depression and significant impairment of anterograde explicit memory. Both propofol and midazolam helped relieve anxiety and lowered blood pressure (compared to baseline) but both were associated with greater dizziness scores (P<0.001, compared to placebo).

They concluded that Propofol had an anxiolytic effect comparable in magnitude and duration to that of midazolam with less memory impairment, respiratory depression and dizziness.

Propofol appears to be an economical, effective and safe alternative to midazolam for treating pre-anesthesia anxiety, and especially to be used for induction of anesthesia (10). (This sentence is not clear).

Therefore, we designed this randomized, double-blind, and placebo-controlled study to evaluate propofol as a premedication and to see if it:

  • produces comparable anxiolytic effects to midazolam when compared to placebo, but with less memory impairment
  • facilitates early recovery profile
  • improves patient's satisfaction with the induction and early recovery from anesthesia.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
139

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Willingness and ability to sign an informed consent document
  • No allergies to midazolam or propofol
  • 18 - 70 years of age
  • American Society of Anesthesiologists (ASA) Class I-III adults of either sex

Exclusion Criteria:

  • Patients with known allergy, hypersensitivity or contraindications to midazolam, propofol, anesthetic or analgesic medications
  • Patients with clinically-significant medical conditions, such as brain, heart, kidney, endocrine, or liver diseases
  • Pregnant or lactating women
  • Subjects with a history of alcohol or drug abuse within the past 3 months
  • Patients chronically using sedative, anxiolytic drugs prior to the surgery
  • Morbid obesity (BMI >40 kg/m2)
  • Patients who are agitated or confused prior to receiving the drug ( verbal rating scale [VRS] greater then 6)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Propofol
Propofol 20 mg IV (2 ml)
Drug: Propofol
Propofol (20mg) 2 ml IV, in the pre-op area as a premedication
Other Names:
  • Diprivan
Active Comparator: Midazolam
Midazolam 2 mg IV (2 ml)
Drug: Midazolam
Midazolam (20mg) 2 ml IV, in the pre-op area as a premedication
Other Names:
  • VERSED
Placebo Comparator: Saline
Saline 2 ml
Drug: Saline
Saline 2 ml IV, in the pre-op area as a premedication
Other Names:
  • Saline solution

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Scores on the Verbal Rating Scale For Anxiety
Time Frame: one day
Using the verbal rating scale (VRS) for anxiety (0= none to 10 = extremely nervous)
one day

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Scores on the Verbal Rating Scale For Sleepiness (Sedation)
Time Frame: one day
Using the verbal rating scale (VRS) for anxiety (0= none to 10 = extremely sleepiness)
one day
Produces Amnesia(Memory Recall)
Time Frame: one day

Ability to recall (memory of):

•recall of 2 pictures
one day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cedars-Sinai Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 30, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 6, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 14, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 17, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Pro00025204

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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