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

NCT ID: NCT00578214

Last Updated: 2012-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2008-06-30

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.

Conditions

Basal Cell Carcinoma; Squamous Cell Carcinoma; Skin Cancer; Anxiety

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Randomized Midazolam

Single-dose midazolam

Group Type: ACTIVE_COMPARATOR

Randomized Midazolam

Intervention Type: DRUG

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.

Local Anesthesia

Intervention Type: DRUG

Lidocaine 1% with 1:100,000 epinephrine

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

The placebo was prepared as a color- and texture-matched cherry flavored syrup without midazolam.

Local Anesthesia

Intervention Type: DRUG

Lidocaine 1% with 1:100,000 epinephrine

Prospective Midazolam

Group Type: EXPERIMENTAL

Local Anesthesia

Intervention Type: DRUG

Lidocaine 1% with 1:100,000 epinephrine

Prospective Midazolam

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Placebo

The placebo was prepared as a color- and texture-matched cherry flavored syrup without midazolam.

Intervention Type: OTHER

Local Anesthesia

Lidocaine 1% with 1:100,000 epinephrine

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Versed; Versed

Eligibility Criteria

Inclusion Criteria

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

• 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

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mayo Clinic

Principal Investigators

Clark C Otley, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Larisa Ravitskiy, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21238825 (View on PubMed)

Other Identifiers

07-000848

Identifier Type: -

Identifier Source: org_study_id