Clinical trial NCT00578214: Safety and Efficacy of Oral Midazolam for Perioperative Anxiety Relief of Patients Undergoing Mohs Micrographic Surgery
Official title: Randomized Controlled and Prospective Studies of Safety and Efficacy of Oral Midazolam for Perioperative Anxiolysis of Patients Undergoing Mohs Micrographic Surgery.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Basal Cell Carcinoma
Squamous Cell Carcinoma
Skin Cancer
Anxiety
Keywords: mohs micrographic surgery
skin cancer
anxiety
basal cell carcinoma
squamous cell carcinoma
midazolam
versed
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2007-12-21
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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)

Primary outcomes:
measure: Patient Anxiety at Baseline
timeFrame: Baseline (prior to drug administration)
measure: Patient Anxiety at 60 and 120 Minutes
timeFrame: 60 and 120 minutes after drug administration
Secondary outcomes:
measure: Patient Alertness at Baseline
timeFrame: Baseline (prior to drug administration)
measure: Patient Alertness at 60 and 120 Minutes
timeFrame: 60 and 120 minutes after drug administration
measure: Patient Cognitive Function at Baseline and 60 Minutes
timeFrame: baseline (prior to drug administration) and 60 minutes after drug administration
measure: Patient Cognitive Function at 120 Minutes
timeFrame: 120 minutes after drug administration
measure: Blood Pressure at 30 Minutes
timeFrame: 30 minutes after drug administration
measure: Heart Rate at 30 Minutes
timeFrame: 30 minutes after drug administration
measure: Respiratory Rate at 30 Minutes
timeFrame: 30 minutes after drug administration
measure: Pulse Oximetry at 30 Minutes
timeFrame: 30 minutes after drug administration
measure: Blood Pressure at 60 Minutes
timeFrame: 60 minutes after drug administration
measure: Heart Rate at 60 Minutes
timeFrame: 60 minutes after drug administration
measure: Respiratory Rate at 60 Minutes
timeFrame: 60 minutes after drug administration
measure: Pulse Oximetry at 60 Minutes
timeFrame: 60 minutes after drug administration
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Clark C Otley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Larisa Ravitskiy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ravitskiy L, Phillips PK, Roenigk RK, Weaver AL, Killian JM, Hoverson Schott A, Otley CC. The use of oral midazolam for perioperative anxiolysis of healthy patients undergoing Mohs surgery: conclusions from randomized controlled and prospective studies. J Am Acad Dermatol. 2011 Feb;64(2):310-22. doi: 10.1016/j.jaad.2010.02.038.