Clinical trial NCT03052660: Impact of Preoperative Midazolam on Outcome of Elderly Patients
Official title: Impact of Preoperative Midazolam on Outcome of Elderly Patients: a Multicentre Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Preanesthetic Medication
Keywords: Midazolam
Anxiety
Clinical trial
Patient Satisfaction
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2017-02-14
Enrollment: 782
Sex: ALL
Minimum age (years): 65
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Global patient satisfaction on the first postoperative day
timeFrame: on the first postoperative day (1 day)
Secondary outcomes:
measure: Cognitive testing
timeFrame: preoperative, day 1 and day 30 after surgery (31 days)
measure: Delirium testing
timeFrame: preoperative, day 1 after surgery (2 days)
measure: Preoperative anxiety
timeFrame: preoperatively (1 day)
measure: Change of health-related quality of life
timeFrame: preoperative and day 30 after surgery (31 days)
measure: Activities of daily living
timeFrame: preoperative and day 30 after surgery (31 days)
measure: Perception of pain, well-being, and sleeping
timeFrame: preoperative until first postoperative day (3 days)
measure: Number of participants with adverse events and serious adverse events
timeFrame: surgery and first postoperative day (2 days)
measure: Patient cooperation
timeFrame: surgery day (1 day)
measure: Anaesthesia related data
timeFrame: surgery day (1 day)
measure: Surgery related data
timeFrame: surgery day (1 day)
measure: Rescue benzodiazepine application
timeFrame: surgery day (1 day)
measure: Patients vital data
timeFrame: surgery day (1 day)
measure: Mortality
timeFrame: 30 days
measure: Major adverse events
timeFrame: 30 days
measure: Hospital length of stay
timeFrame: on postoperative day 30 (1 day)
measure: Intensive care unit length of stay
timeFrame: on postoperative day 30 (1 day)
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Department of Anesthesiology, University Hospital Aachen
state: NRW
city: Bonn
country: Germany
facility: Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn
state: NRW
city: Dusseldorf
country: Germany
facility: Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf
state: NRW
city: Herne
country: Germany
facility: Marien-Hospital Herne
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg A.ö.R.
city: Munich
country: Germany
facility: Department of Anaesthesiology, University Hospital Klinikum rechts der Isar Munich
city: München
country: Germany
facility: LMU München
city: Reutlingen
country: Germany
facility: Kreiskliniken Reutlingen, Klinikum am steinenberg
city: Tubingen
country: Germany
facility: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Tübingen
Study officials:
affiliation: Department of Anesthesiology, University Hospital Aachen, Germany
name: Mark Coburn, Professor
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: Wang ML, Min J, Sands LP, Leung JM; the Perioperative Medicine Research Group. Midazolam Premedication Immediately Before Surgery Is Not Associated With Early Postoperative Delirium. Anesth Analg. 2021 Sep 1;133(3):765-771. doi: 10.1213/ANE.0000000000005482.
citation: Kowark A, Rossaint R, Keszei AP, Bischoff P, Czaplik M, Drexler B, Kienbaum P, Kretzschmar M, Rex C, Saller T, Schneider G, Soehle M, Coburn M; I-PROMOTE study group. Impact of PReOperative Midazolam on OuTcome of Elderly patients (I-PROMOTE): study protocol for a multicentre randomised controlled trial. Trials. 2019 Jul 15;20(1):430. doi: 10.1186/s13063-019-3512-3.