Impact of Preoperative Midazolam on Outcome of Elderly Patients

NCT ID: NCT03052660

Last Updated: 2019-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 782 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-12
• Study Completion Date: 2019-06-24

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.

Conditions

Preanesthetic Medication

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Midazolam

Midazolam, 3.75 mg , oral, once, 30-45 minutes before surgery

Group Type: EXPERIMENTAL

Midazolam

Intervention Type: DRUG

Oral administration preoperatively

Placebo

Placebo, oral, once, 30-45 minutes before surgery

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Oral administration preoperatively

Interventions

Midazolam

Oral administration preoperatively

Intervention Type: DRUG

Placebo oral capsule

Oral administration preoperatively

Intervention Type: DRUG

Other Intervention Names

Dormicum

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

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RWTH Aachen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Coburn, Professor

Role: STUDY_CHAIR

Department of Anesthesiology, University Hospital Aachen, Germany

Locations

Department of Anesthesiology, University Hospital Aachen

Aachen, North Rhine-Westphalia, Germany

Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia, Germany

Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf

Düsseldorf, North Rhine-Westphalia, Germany

Marien-Hospital Herne

Herne, , 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

Tübingen, , Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 15915023 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25495432 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25734733 (View on PubMed)

Kowark A, Keszei AP, Schneider G, Pilge S, Schneider F, Obert DP, Georgii MT, Heim M, Rossaint R, Ziemann S, van Waesberghe J, Czaplik M, Puhringer FK, Minarski C, May V, Malisi T, Drexler B, Ring CM, Engler P, Tilly R, Bischoff P, Frey U, Wittmann M, Soehle M, Saller T, Kienbaum P, Kretzschmar M, Coburn M; I-PROMOTE Study Group. Preoperative Midazolam and Patient-Centered Outcomes of Older Patients: The I-PROMOTE Randomized Clinical Trial. JAMA Surg. 2024 Feb 1;159(2):129-138. doi: 10.1001/jamasurg.2023.6479.

Reference Type: DERIVED

PMID: 38117527 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33721875 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31307505 (View on PubMed)

Other Identifiers

16-115

Identifier Type: -

Identifier Source: org_study_id