Impact of Preoperative Midazolam on Outcome of Elderly Patients

Phase 4

Completed

• Conditions: Preanesthetic Medication
• Interventions: Drug: Placebo oral capsule; Drug: Midazolam

• Registration Number: NCT03052660
• Lead Sponsor: RWTH Aachen University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-02-07
• Study First Submitted QC: 2017-02-09
• Study First Posted: 2017-02-14
• Study Start: 2017-10-12
• Primary Completion: 2019-06-24
• Study Completion: 2019-06-24
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-14
• Last Update Posted: 2019-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 782

Inclusion Criteria

1. 1. Only legally competent patients
2. Written informed consent prior to study participation
3. 65-80 years
4. Elective surgery
5. Expected surgery duration ≥ 30 minutes
6. Planned general or combined regional and general anaesthesia
7. Planned extubation at the end of surgery

Exclusion Criteria

1. Age > 80 years
2. Age < 65 years
3. Non-fluency in German language
4. Alcohol and/ or drugs abuse
5. Chronic benzodiazepine treatment
6. Intracranial surgery
7. Local and stand by anaesthesia or solely regional anaesthesia
8. Monitored anaesthesia care
9. Cardiac surgery
10. Ambulatory surgery
11. Repeated surgery
12. Contraindications for benzodiazepine application (e.g. sleep apnoea syndrome, severe chronic obstructive pulmonary disease, allergy)
13. 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).
14. Expected benzodiazepine requirement after surgery
15. Expected continuous mandatory ventilation after surgery
16. Patients who explicitly request anxiolytic premedication
17. Patients with severe neurological or psychiatric disorders
18. Refusal of study participation by the patient
19. Parallel participation in interventional clinical studies within the last 30 days

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo oral capsule	Placebo, oral, once, 30-45 minutes before surgery
Midazolam	Midazolam	Midazolam, 3.75 mg , oral, once, 30-45 minutes before surgery

Primary Outcome Measures

Name	Time	Method
Global patient satisfaction on the first postoperative day	on the first postoperative day (1 day)	measured with the EVAN-G questionnaire on the first postoperative day

Secondary Outcome Measures

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

Trial Locations

Locations (9)

Department of Anesthesiology, University Hospital Aachen; 🇩🇪 Aachen, NRW, Germany

Marien-Hospital Herne; 🇩🇪 Herne, Germany

Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn; 🇩🇪 Bonn, NRW, Germany

Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf; 🇩🇪 Dusseldorf, NRW, Germany

Universitätsklinikum Magdeburg A.ö.R.; 🇩🇪 Magdeburg, Germany

Department of Anaesthesiology, University Hospital Klinikum rechts der Isar Munich; 🇩🇪 Munich, Germany

LMU München; 🇩🇪 München, Germany

Kreiskliniken Reutlingen, Klinikum am steinenberg; 🇩🇪 Reutlingen, Germany

Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Tübingen; 🇩🇪 Tubingen, Germany