Impact of Preoperative Midazolam on Outcome of Elderly Patients

Preanesthetic Medication Clinical Trial

— I-PROMOTE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03052660
• Other study ID #: 16-115
• Status: Completed
• Phase: Phase 4
• Start date: October 12, 2017
• Est. completion date: June 24, 2019

Study information

• Verified date: November 2019
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 782
• Est. completion date: June 24, 2019
• Est. primary completion date: June 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Preanesthetic Medication

Intervention

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

Locations

Country	Name	City	State
Germany	Department of Anesthesiology, University Hospital Aachen	Aachen	NRW
Germany	Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn	Bonn	NRW
Germany	Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf	Dusseldorf	NRW
Germany	Marien-Hospital Herne	Herne
Germany	Universitätsklinikum Magdeburg A.ö.R.	Magdeburg
Germany	LMU München	München
Germany	Department of Anaesthesiology, University Hospital Klinikum rechts der Isar Munich	Munich
Germany	Kreiskliniken Reutlingen, Klinikum am steinenberg	Reutlingen
Germany	Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Tübingen	Tubingen

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

References & Publications (3)

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.13 — View Citation

Auquier P, Pernoud N, Bruder N, Simeoni MC, Auffray JP, Colavolpe C, François 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. — View 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 — View Citation

Outcome

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