Preanesthetic MedicationPhase 4I-PROMOTENCT03052660
Impact of Preoperative Midazolam on Outcome of Elderly Patients
A Phase 4 study testing Midazolam in people with Preanesthetic Medication, run by RWTH Aachen University at 9 sites in Germany.
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 Read more about this study
- Who is it for?
- Ages 65 to 80 years
- Conditions the study is for
- Preanesthetic Medication
- What is being tested?
- Midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 782 participants
- Where
- 9 sitesGermany
- Study dates
- 12 Oct 2017to 24 Jun 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 80 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 1. Only legally competent patients
- Written informed consent prior to study participation
- 65-80 years
- Elective surgery
- Expected surgery duration ≥ 30 minutes
- Planned general or combined regional and general anaesthesia
- Planned extubation at the end of surgery
Who cannot join
- Age > 80 years
- Age < 65 years
- Non-fluency in German language
- Alcohol and/ or drugs abuse
- Chronic benzodiazepine treatment
- Intracranial surgery
Show all 19Show fewer
- Local and stand by anaesthesia or solely regional anaesthesia
- Monitored anaesthesia care
- Cardiac surgery
- Ambulatory surgery
- Repeated surgery
- Contraindications for benzodiazepine application (e.g. sleep apnoea syndrome, severe chronic obstructive pulmonary disease, allergy)
- 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).
- Expected benzodiazepine requirement after surgery
- Expected continuous mandatory ventilation after surgery
- Patients who explicitly request anxiolytic premedication
- Patients with severe neurological or psychiatric disorders
- Refusal of study participation by the patient
- Parallel participation in interventional clinical studies within the last 30 days
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Germany9 sites
Department of Anesthesiology, University Hospital Aachen
Aachen, North Rhine-Westphalia, 52074
Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn
Bonn, North Rhine-Westphalia, 53127
Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf
Düsseldorf, North Rhine-Westphalia, 40225
Marien-Hospital Herne
Herne, 44625
Universitätsklinikum Magdeburg A.ö.R.
Magdeburg, 39120
LMU München
München, 81377
Department of Anaesthesiology, University Hospital Klinikum rechts der Isar Munich
Munich, 81675
Kreiskliniken Reutlingen, Klinikum am steinenberg
Reutlingen, 72764
Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Tübingen
Tübingen, 72076
About this study
Official title: Impact of Preoperative Midazolam on Outcome of Elderly Patients: a Multicentre Randomised Controlled Trial
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
Read the 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
- Being tested
- Midazolam, Placebo oral capsule
- Keywords
- Midazolam, Anxiety, Clinical trial, Patient Satisfaction
- Medical subject headings
- Anxiety Disorders, Patient Satisfaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidazolamDrug
Also called Dormicum
Oral administration preoperatively
Placebo oral capsuleDrug
Oral administration preoperatively
| Study group | Role | What they receive |
|---|---|---|
| Midazolam | Experimental | Midazolam, 3.75 mg , oral, once, 30-45 minutes before surgery Receives: Drug: Midazolam |
| Placebo | Placebo comparator | Placebo, oral, once, 30-45 minutes before surgery Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Global patient satisfaction on the first postoperative day
measured with the EVAN-G questionnaire on the first postoperative day
Measured: on the first postoperative day (1 day)
Secondary outcomes (16)
Cognitive testing
Measured by the short blessed test
Measured: preoperative, day 1 and day 30 after surgery (31 days)
Delirium testing
Measured by Confusion Assessment Method (CAM)
Measured: preoperative, day 1 after surgery (2 days)
Preoperative anxiety
Measured by Amsterdam Preoperative Anxiety and Information Scale (APAIS)
Measured: preoperatively (1 day)
Change of health-related quality of life
Measured by the individual health-related quality of life assessment EQ-5D-5L
Measured: preoperative and day 30 after surgery (31 days)
Activities of daily living
Measured by Instrumental Activities of Daily Living scale (IADL)
Measured: preoperative and day 30 after surgery (31 days)
Perception of pain, well-being, and sleeping
Self-reported by visual analogue scale (VAS)
Measured: preoperative until first postoperative day (3 days)
Number of participants with adverse events and serious adverse events
Review of medical charts and patient interview
Measured: surgery and first postoperative day (2 days)
Patient cooperation
Self-reported by visual analogue scale (VAS) by the attending anesthetist
Measured: surgery day (1 day)
Anaesthesia related data
Anesthesia drugs, type of anesthesia, duration, extubation-time
Measured: surgery day (1 day)
Surgery related data
Duration and kind of surgery
Measured: surgery day (1 day)
Rescue benzodiazepine application
assessment of additional requirement of midazolam in the operating area
Measured: surgery day (1 day)
Patients vital data
Measurement of SpO2, RRsys, HR on arrival in the operating room and at the end of surgery
Measured: surgery day (1 day)
Mortality
Patient chart review and telephone interview after discharge
Measured: 30 days
Major adverse events
Assessment of postoperative major adverse cardiovascular and cerebral events by patient chart review and telephone interview after discharge
Measured: 30 days
Hospital length of stay
Patient chart review
Measured: on postoperative day 30 (1 day)
Intensive care unit length of stay
Patient chart review
Measured: on postoperative day 30 (1 day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2017
- Study start12 Oct 2017
- Primary completion24 Jun 2019
- Study completion24 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Preanesthetic MedicationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 782 participants (actual)
Sponsor and investigators
- Lead sponsor
- RWTH Aachen University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Coburn, Professor, Study chair, Department of Anesthesiology, University Hospital Aachen, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03052660
- Sponsor's protocol ID
- 16-115
- Acronym
- I-PROMOTE
- Status last verified
- Nov 2019
- First submitted
- 7 Feb 2017
- Last updated
- 18 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 15915023American 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.
PubMed 25495432Maurice-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.
PubMed 25734733Kowark 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.
PubMed 38117527Wang 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.
PubMed 33721875Kowark 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.
PubMed 31307505
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Preoperative Midazolam on Outcome of Elderly Patients: a Multicentre Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT03052660
- Acronym / sponsor ID
- I-PROMOTE / 16-115
- Conditions
- Preanesthetic Medication
- Keywords
- Midazolam, Anxiety, Clinical trial, Patient Satisfaction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 782 participants (actual)
- Lead sponsor
- RWTH Aachen UniversityUniversity, hospital or other
- Study start
- 12 Oct 2017 (actual)
- Primary completion
- 24 Jun 2019 (actual)
- Study completion
- 24 Jun 2019 (actual)
- First posted
- 14 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Midazolam | Experimental | Drug: MidazolamMidazolam, 3.75 mg , oral, once, 30-45 minutes before surgery |
| Placebo | Placebo comparator | Drug: Placebo oral capsulePlacebo, oral, once, 30-45 minutes before surgery |
Who may qualify
- Ages
- 65 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (7 listed)
- 1. Only legally competent patients
- Written informed consent prior to study participation
- 65-80 years
- Elective surgery
- Expected surgery duration ≥ 30 minutes
Key exclusion criteria (19 listed)
- Age > 80 years
- Age < 65 years
- Non-fluency in German language
- Alcohol and/ or drugs abuse
- Chronic benzodiazepine treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MidazolamAlso: DormicumOral administration preoperatively | Drug | Midazolam |
| Placebo oral capsuleOral administration preoperatively | Drug | Placebo |
Primary outcome
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
16 secondary outcomes
Cognitive testing
Time frame: preoperative, day 1 and day 30 after surgery (31 days)
Delirium testing
Time frame: preoperative, day 1 after surgery (2 days)
Preoperative anxiety
Time frame: preoperatively (1 day)
Change of health-related quality of life
Time frame: preoperative and day 30 after surgery (31 days)
Activities of daily living
Time frame: preoperative and day 30 after surgery (31 days)
Perception of pain, well-being, and sleeping
Time frame: preoperative until first postoperative day (3 days)
Number of participants with adverse events and serious adverse events
Time frame: surgery and first postoperative day (2 days)
Patient cooperation
Time frame: surgery day (1 day)
Anaesthesia related data
Time frame: surgery day (1 day)
Surgery related data
Time frame: surgery day (1 day)
Rescue benzodiazepine application
Time frame: surgery day (1 day)
Patients vital data
Time frame: surgery day (1 day)
Mortality
Time frame: 30 days
Major adverse events
Time frame: 30 days
Hospital length of stay
Time frame: on postoperative day 30 (1 day)
Intensive care unit length of stay
Time frame: on postoperative day 30 (1 day)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2019.
- Results publication: PubMed 15915023Auquier 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.
- Results publication: PubMed 25495432American 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.
- Results publication: PubMed 25734733Maurice-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.
- Derived from this study: PubMed 38117527Kowark 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.
- Derived from this study: PubMed 33721875Wang 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.
- Derived from this study: PubMed 31307505Kowark 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Coburn, Professor study chair
Department of Anesthesiology, University Hospital Aachen, Germany
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Midazolam in people with Preanesthetic Medication, run by RWTH Aachen University at 9 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Global patient satisfaction on the first postoperative day (time frame: on the first postoperative day (1 day)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03052660, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2019.