Safety and Efficacy of Oral Midazolam for Perioperative Anxiety Relief of Patients Undergoing Mohs Micrographic Surgery

This study has been completed.
Sponsor:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00578214
First received: December 20, 2007
Last updated: February 8, 2012
Last verified: February 2012
  Purpose

Midazolam is an approved sedative medication used for medical procedures. This study was being done to document the safety and efficacy of midazolam in improving anxiety, heart rate, and blood pressure in patients prior to undergoing Mohs micrographic surgery for the treatment of skin cancer (basal cell carcinoma or squamous cell carcinoma). Midazolam may make a patient relaxed and sleepy, and lower blood pressure. These effects last for about 2 hours.

This study had two parts. In the first part, eligible patients were randomized to either receiving one standard dose of midazolam syrup or placebo syrup before their surgery, with neither the patient nor the study team knowing which patient received the study drug. In the second part, patients who were not eligible to participate in the randomized study or who refused to participate in the randomized study were enrolled in a prospective arm where they knew they were receiving midazolam syrup. In the prospective arm, the doses were based on the patient's weight, and patients were given additional doses of midazolam syrup as necessary to control their anxiety.

The primary hypothesis of this study was that a single dose of oral midazolam syrup to patients prior undergoing outpatient Mohs micrographic surgery for skin cancer would result in lower anxiety scores at 60 minutes compared to placebo. In addition, the second hypothesis of this study was that patients given oral midazolam would have the rate of adverse events that was not worse than 25% higher than in the placebo group.


Condition Intervention
Basal Cell Carcinoma
Squamous Cell Carcinoma
Skin Cancer
Anxiety
Drug: Randomized Midazolam
Other: Placebo
Drug: Local Anesthesia
Drug: Prospective Midazolam

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Controlled and Prospective Studies of Safety and Efficacy of Oral Midazolam for Perioperative Anxiolysis of Patients Undergoing Mohs Micrographic Surgery.

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Patient Anxiety at Baseline [ Time Frame: Baseline (prior to drug administration) ] [ Designated as safety issue: No ]
    A 10-point visual analog scale (VAS) was used to measure anxiety. The patients marked on the scale their feeling of anxiety. The lowest value possible was 0 (no anxiety) and the highest value possible was 10 (highest possible anxiety).

  • Patient Anxiety at 60 and 120 Minutes [ Time Frame: 60 and 120 minutes after drug administration ] [ Designated as safety issue: No ]
    A 10-point visual analog scale (VAS) was used to measure anxiety. The patients marked on the scale their feeling of anxiety. The lowest value possible was 0 (no anxiety) and the highest value possible was 10 (highest possible anxiety).


Secondary Outcome Measures:
  • Patient Alertness at Baseline [ Time Frame: Baseline (prior to drug administration) ] [ Designated as safety issue: No ]
    A 10-point visual analog scale (VAS) was used to measure alertness. The patients marked on the scale their feeling of alertness. The lowest value possible was 0 (awake) and the highest value possible was 10 (barely awake).

  • Patient Alertness at 60 and 120 Minutes [ Time Frame: 60 and 120 minutes after drug administration ] [ Designated as safety issue: No ]
    A 10-point visual analog scale (VAS) was used to measure alertness. The patients marked on the scale their feeling of alertness. The lowest value possible was 0 (awake) and the highest value possible was 10 (barely awake).

  • Patient Cognitive Function at Baseline and 60 Minutes [ Time Frame: baseline (prior to drug administration) and 60 minutes after drug administration ] [ Designated as safety issue: No ]
    Cognitive function was measured by the Mini-Mental State Examination (MMSE), a brief 30 point questionnaire test. The scores can range from 0 (low cognitive function) to 30 (high cognitive function).

  • Patient Cognitive Function at 120 Minutes [ Time Frame: 120 minutes after drug administration ] [ Designated as safety issue: No ]
    Cognitive function was measured by the Mini-Mental State Examination (MMSE), a brief 30 point questionnaire test. The scores can range from 0 (low cognitive function) to 30 (high cognitive function).

  • Blood Pressure at 30 Minutes [ Time Frame: 30 minutes after drug administration ] [ Designated as safety issue: Yes ]
  • Heart Rate at 30 Minutes [ Time Frame: 30 minutes after drug administration ] [ Designated as safety issue: Yes ]
  • Respiratory Rate at 30 Minutes [ Time Frame: 30 minutes after drug administration ] [ Designated as safety issue: Yes ]
  • Pulse Oximetry at 30 Minutes [ Time Frame: 30 minutes after drug administration ] [ Designated as safety issue: Yes ]
    Pulse oximetry measures the oxygenation of a patient's hemoglobin. A sensor is placed on the patient's finger. Light at red and infrared wavelengths is passed sequentially through the patient to a photodetector. The changing absorbance at each of the two wavelengths is measured, allowing determination of the absorbance. The color of the blood provides a measure of oxygenation (the percentage of hemoglobin molecules bound with oxygen molecules). A healthy young person will probably have an oxygen saturation of 95-99%.

  • Blood Pressure at 60 Minutes [ Time Frame: 60 minutes after drug administration ] [ Designated as safety issue: Yes ]
  • Heart Rate at 60 Minutes [ Time Frame: 60 minutes after drug administration ] [ Designated as safety issue: Yes ]
  • Respiratory Rate at 60 Minutes [ Time Frame: 60 minutes after drug administration ] [ Designated as safety issue: Yes ]
  • Pulse Oximetry at 60 Minutes [ Time Frame: 60 minutes after drug administration ] [ Designated as safety issue: Yes ]
    Pulse oximetry measures the oxygenation of a patient's hemoglobin. A sensor is placed on the patient's finger. Light at red and infrared wavelengths is passed sequentially through the patient to a photodetector. The changing absorbance at each of the two wavelengths is measured, allowing determination of the absorbance. The color of the blood provides a measure of oxygenation (the percentage of hemoglobin molecules bound with oxygen molecules). A healthy young person will probably have an oxygen saturation of 95-99%.


Enrollment: 75
Study Start Date: March 2007
Study Completion Date: June 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Randomized Midazolam
Single-dose midazolam
Drug: Randomized Midazolam
Midazolam was prepared in a 2 mg/ml cherry flavored syrup. In the randomized arm, patients received a single-dose administration of 5 ml (10 mg) of the midazolam syrup.
Other Name: Versed
Drug: Local Anesthesia
Lidocaine 1% with 1:100,000 epinephrine
Placebo Comparator: Placebo Other: Placebo
The placebo was prepared as a color- and texture-matched cherry flavored syrup without midazolam.
Drug: Local Anesthesia
Lidocaine 1% with 1:100,000 epinephrine
Experimental: Prospective Midazolam Drug: Local Anesthesia
Lidocaine 1% with 1:100,000 epinephrine
Drug: Prospective Midazolam
Midazolam was prepared in a 2 mg/ml cherry flavored syrup. Dosing in the prospective arm was based on weight (>45 to 77 kg, 10 mg; >77 to 100 kg, 15 mg; greater than or equal to 100 kg, 20 mg). In the prospective arm patients were given additional doses of midazolam as necessary (in 5 mg increments) to achieve and maintain the desired level of anxiolysis.
Other Name: Versed

Detailed Description:

The main objective of this study was to establish the safety and efficacy of midazolam in patients with skin cancer undergoing outpatient Mohs micrographic surgery. Patients were randomized in a double-blind placebo-controlled study of a single-dose midazolam syrup for efficacy in producing safe anxiolysis of short duration. A parallel prospective arm of the study involved administration of midazolam in an unblinded fashion. Based on available studies of orally administered midazolam, the expectation was that the only observed adverse events will be minor and the major adverse event rate for midazolam would be similar to placebo. Data was collected on vital signs, anxiety, adverse events, and overall satisfaction with the anxiolytic agent.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- 1 or 2 sites of biopsy-confirmed squamous cell or basal cell carcinomas limited to head and neck regions

Inclusion Criteria for Prospective Arm:

  • Patients wishing to receive oral midazolam in a non-blinded fashion will not be excluded based on the size of an individual tumor, total number of tumors, or prior history of oral midazolam
  • No upper weight limitation

Exclusion Criteria:

  • Prior history of allergy to midazolam or any of the syrup components
  • History of hypersensitivity to other benzodiazepines
  • Congestive heart failure (AHA Class III and IV)
  • Renal failure requiring hemodialysis
  • End-stage liver failure
  • Chronic alcoholism or alcohol intoxication within 24 hours of surgery
  • Untreated or uncontrolled open angle glaucoma
  • Uncontrolled hypertension
  • History of psychoses or affective disorders
  • Neuromuscular disorders such as myasthenia gravis
  • Chronic obstructive pulmonary disease
  • Patients on medications interfering with renal excretion or microsomal metabolism unless the last dose was taken greater than or equal to 5 half-lives prior to surgery
  • Patients weighing less than 100 lb (45 kg)
  • Pregnant women; women of childbearing potential will be required to take an in-office urine pregnancy test.
  • Breast-feeding mothers must stop breast-feeding for 7 days after taking midazolam to take part in this study

Additional Exclusion Criteria for Randomized Arms:

  • Patients with a single cancer > 5 cm in the greatest dimension or with more than 2 cancers
  • Patients who were previously premedicated with oral midazolam during prior Mohs micrographic surgery episodes
  • Patients weighing more than 220 lb (100 kg)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00578214

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Clark C Otley, MD Mayo Clinic
Principal Investigator: Larisa Ravitskiy, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Larisa Ravitskiy, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00578214     History of Changes
Other Study ID Numbers: 07-000848
Study First Received: December 20, 2007
Results First Received: January 13, 2012
Last Updated: February 8, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
mohs micrographic surgery
skin cancer
anxiety
basal cell carcinoma
squamous cell carcinoma
midazolam
versed

Additional relevant MeSH terms:
Anxiety Disorders
Carcinoma
Skin Neoplasms
Carcinoma, Basal Cell
Carcinoma, Squamous Cell
Mental Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Skin Diseases
Neoplasms, Basal Cell
Neoplasms, Squamous Cell
Anesthetics
Midazolam
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
GABA Modulators
GABA Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on August 26, 2014