Impact of Preoperative Midazolam on Outcome of Elderly Patients (I-PROMOTE)

• ClinicalTrials.gov Identifier: NCT03052660
• Recruitment Status: Completed
• First Posted: February 14, 2017
• Last Update Posted: November 18, 2019
• Sponsor: RWTH Aachen University
• Information provided by (Responsible Party): RWTH Aachen University

Study Description

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

Condition or disease	Intervention/treatment	Phase
Preanesthetic Medication	Drug: Midazolam; Drug: Placebo oral capsule	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 782 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Impact of Preoperative Midazolam on Outcome of Elderly Patients: a Multicentre Randomised Controlled Trial
• Actual Study Start Date: October 12, 2017
• Actual Primary Completion Date: June 24, 2019
• Actual Study Completion Date: June 24, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Midazolam; Midazolam, 3.75 mg , oral, once, 30-45 minutes before surgery	Drug: Midazolam; Oral administration preoperatively; Other Name: Dormicum
Placebo Comparator: Placebo; Placebo, oral, once, 30-45 minutes before surgery	Drug: Placebo oral capsule; Oral administration preoperatively

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. Cognitive testing [ Time Frame: preoperative, day 1 and day 30 after surgery (31 days) ]
   Measured by the short blessed test
2. Delirium testing [ Time Frame: preoperative, day 1 after surgery (2 days) ]
   Measured by Confusion Assessment Method (CAM)
3. Preoperative anxiety [ Time Frame: preoperatively (1 day) ]
   Measured by Amsterdam Preoperative Anxiety and Information Scale (APAIS)
4. 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
5. Activities of daily living [ Time Frame: preoperative and day 30 after surgery (31 days) ]
   Measured by Instrumental Activities of Daily Living scale (IADL)
6. Perception of pain, well-being, and sleeping [ Time Frame: preoperative until first postoperative day (3 days) ]
   Self-reported by visual analogue scale (VAS)
7. 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
8. Patient cooperation [ Time Frame: surgery day (1 day) ]
   Self-reported by visual analogue scale (VAS) by the attending anesthetist
9. Anaesthesia related data [ Time Frame: surgery day (1 day) ]
   Anesthesia drugs, type of anesthesia, duration, extubation-time
10. Surgery related data [ Time Frame: surgery day (1 day) ]
    Duration and kind of surgery
11. Rescue benzodiazepine application [ Time Frame: surgery day (1 day) ]
    assessment of additional requirement of midazolam in the operating area
12. 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
13. Mortality [ Time Frame: 30 days ]
    Patient chart review and telephone interview after discharge
14. 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
15. Hospital length of stay [ Time Frame: on postoperative day 30 (1 day) ]
    Patient chart review
16. Intensive care unit length of stay [ Time Frame: on postoperative day 30 (1 day) ]
    Patient chart review

Eligibility Criteria

• Ages Eligible for Study: 65 Years to 80 Years (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Germany

Department of Anesthesiology, University Hospital Aachen

Aachen, NRW, Germany, 52074

Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn

Bonn, NRW, Germany, 53127

Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf

Dusseldorf, NRW, Germany, 40225

Marien-Hospital Herne

Herne, Germany, 44625

Universitätsklinikum Magdeburg A.ö.R.

Magdeburg, Germany, 39120

Department of Anaesthesiology, University Hospital Klinikum rechts der Isar Munich

Munich, Germany, 81675

LMU München

München, Germany, 81377

Kreiskliniken Reutlingen, Klinikum am steinenberg

Reutlingen, Germany, 72764

Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Tübingen

Tubingen, Germany, 72076

Sponsors and Collaborators

RWTH Aachen University

Investigators

• Study Chair: Mark Coburn, Professor; Department of Anesthesiology, University Hospital Aachen, Germany

More Information

Publications of 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wang ML, Min J, Sands LP, Leung JM; 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.

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.

• Responsible Party: RWTH Aachen University
• ClinicalTrials.gov Identifier: NCT03052660
• Other Study ID Numbers: 16-115
• First Posted: February 14, 2017
• Last Update Posted: November 18, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by RWTH Aachen University:

Midazolam; Anxiety; Clinical trial; Patient Satisfaction

Additional relevant MeSH terms:

Midazolam; Adjuvants, Anesthesia; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action