Impact of Preoperative Midazolam on Outcome of Elderly Patients

Study Overview
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Brief Summary
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We aim to assess, if placebo compared to preoperative administration of midazolam in elderly patients is equal in regard to the global postoperative patient satisfaction

Detailed Description
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Generalised premedication with benzodiazepines in all surgical patients has become questionable, regarding the risk-benefit assessment and the lack of evidence for this practice. Particularly, in elderly patients (≥65 years), a higher risk for adverse events is described. Patients will be randomly assigned to one of the following two study groups. Preoperatively, group 1 will receive midazolam and group 2 will receive placebo. Anaesthesia will be performed according to the clinical routine. All possible side effects are described in the SmPC for midazolam. For the placebo-group, we do not expect any harm, as in the case of strong preoperative anxiety or agitation, additional midazolam application may occur on behalf of the attending anaesthesist at any time. The sample size was calculated based on detecting a minimum of 5 unit difference in the primary outcome variable overall patient satisfaction measured with the EVAN-G. Setting a type 1 error of 0.05, a power of 0.8 and assuming the standard deviation of EVAN-G to be 14 units, 248 patients per group are needed to detect a 5 unit difference. Considering a drop-out of 10% and a screening failure of 10%, we decided to include 614 patients in total. The hypothesis of the study is that global patient satisfaction after surgery in elderly patients is similar after preoperative placebo application compared to midazolam application.

Official Title
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Impact of Preoperative Midazolam on Outcome of Elderly Patients: a Multicentre Randomised Controlled Trial

Conditions
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Preanesthetic Medication

Intervention / Treatment
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* Drug: Midazolam
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Only legally competent patients Written informed consent prior to study participation 65-80 years Elective surgery Expected surgery duration ≥ 30 minutes Planned general or combined regional and general anaesthesia Planned extubation at the end of surgery Exclusion Criteria: Age > 80 years Age < 65 years Non-fluency in German language Alcohol and/ or drugs abuse Chronic benzodiazepine treatment Intracranial surgery Local and stand by anaesthesia or solely regional anaesthesia Monitored anaesthesia care Cardiac surgery Ambulatory surgery Repeated surgery Contraindications for benzodiazepine application (e.g. sleep apnoea syndrome, severe chronic obstructive pulmonary disease, allergy) Allergy against any component of the Placebo (lactose monohydrate, cellulose powder, magnesium stearate, microcrystalline cellulose) or investigational drug (midazolam, lactose) or the capsules (gelatine, E171 titanium dioxide, E132 indigotine). Expected benzodiazepine requirement after surgery Expected continuous mandatory ventilation after surgery Patients who explicitly request anxiolytic premedication Patients with severe neurological or psychiatric disorders Refusal of study participation by the patient Parallel participation in interventional clinical studies within the last 30 days

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midazolam<br>Midazolam, 3.75 mg , oral, once, 30-45 minutes before surgery | Drug: Midazolam<br>* Oral administration preoperatively<br>* Other names: Dormicum;|
| Placebo Comparator: Placebo<br>Placebo, oral, once, 30-45 minutes before surgery | Drug: Placebo oral capsule<br>* Oral administration preoperatively<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global patient satisfaction on the first postoperative day | measured with the EVAN-G questionnaire on the first postoperative day | on the first postoperative day (1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive testing | Measured by the short blessed test | preoperative, day 1 and day 30 after surgery (31 days) | 
| Delirium testing | Measured by Confusion Assessment Method (CAM) | preoperative, day 1 after surgery (2 days) | 
| Preoperative anxiety | Measured by Amsterdam Preoperative Anxiety and Information Scale (APAIS) | preoperatively (1 day) | 
| Change of health-related quality of life | Measured by the individual health-related quality of life assessment EQ-5D-5L | preoperative and day 30 after surgery (31 days) | 
| Activities of daily living | Measured by Instrumental Activities of Daily Living scale (IADL) | preoperative and day 30 after surgery (31 days) | 
| Perception of pain, well-being, and sleeping | Self-reported by visual analogue scale (VAS) | preoperative until first postoperative day (3 days) | 
| Number of participants with adverse events and serious adverse events | Review of medical charts and patient interview | surgery and first postoperative day (2 days) | 
| Patient cooperation | Self-reported by visual analogue scale (VAS) by the attending anesthetist | surgery day (1 day) | 
| Anaesthesia related data | Anesthesia drugs, type of anesthesia, duration, extubation-time | surgery day (1 day) | 
| Surgery related data | Duration and kind of surgery | surgery day (1 day) | 
| Rescue benzodiazepine application | assessment of additional requirement of midazolam in the operating area | surgery day (1 day) | 
| Patients vital data | Measurement of SpO2, RRsys, HR on arrival in the operating room and at the end of surgery | surgery day (1 day) | 
| Mortality | Patient chart review and telephone interview after discharge | 30 days | 
| Major adverse events | Assessment of postoperative major adverse cardiovascular and cerebral events by patient chart review and telephone interview after discharge | 30 days | 
| Hospital length of stay | Patient chart review | on postoperative day 30 (1 day) | 
| Intensive care unit length of stay | Patient chart review | on postoperative day 30 (1 day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Midazolam, Anxiety, Clinical trial, Patient Satisfaction