Impact of Preoperative Midazolam on Outcome of Elderly Patients

Overview

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

Full Title of Study: “Impact of Preoperative Midazolam on Outcome of Elderly Patients: a Multicentre Randomised Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: June 24, 2019

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.

Interventions

  • Drug: Midazolam
    • Oral administration preoperatively
  • Drug: Placebo oral capsule
    • Oral administration preoperatively

Arms, Groups and Cohorts

  • Experimental: Midazolam
    • Midazolam, 3.75 mg , oral, once, 30-45 minutes before surgery
  • Placebo Comparator: Placebo
    • Placebo, oral, once, 30-45 minutes before surgery

Clinical Trial Outcome Measures

Primary Measures

  • Global patient satisfaction on the first postoperative day
    • Time Frame: on the first postoperative day (1 day)
    • measured with the EVAN-G questionnaire on the first postoperative day

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 65 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • RWTH Aachen University
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Mark Coburn, Professor, Study Chair, Department of Anesthesiology, University Hospital Aachen, Germany

Citations Reporting on Results

Auquier P, Pernoud N, Bruder N, Simeoni MC, Auffray JP, Colavolpe C, Francois G, Gouin F, Manelli JC, Martin C, Sapin C, Blache JL. Development and validation of a perioperative satisfaction questionnaire. Anesthesiology. 2005 Jun;102(6):1116-23. doi: 10.1097/00000542-200506000-00010.

American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. American Geriatrics Society abstracted clinical practice guideline for postoperative delirium in older adults. J Am Geriatr Soc. 2015 Jan;63(1):142-50. doi: 10.1111/jgs.13281. Epub 2014 Dec 12.

Maurice-Szamburski A, Auquier P, Viarre-Oreal V, Cuvillon P, Carles M, Ripart J, Honore S, Triglia T, Loundou A, Leone M, Bruder N; PremedX Study Investigators. Effect of sedative premedication on patient experience after general anesthesia: a randomized clinical trial. JAMA. 2015 Mar 3;313(9):916-25. doi: 10.1001/jama.2015.1108.

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