Efficacy and Safety of Oral Midazolam for Providing Care to Patients Who Refuse Treatment and Have Moderately Severe to Severe Neurocognitive Disorders

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Grenoble Alpes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

21 Apr 2026 → ongoing

Decision date (initial)

2024-05-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-510277-33-00

ClinicalTrials.gov

NCT06638710

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluation of the efficacy of oral midazolam in facilitating care delivery for elderly patients with moderate-to-severe neurocognitive disorders who resist care.

Secondary objectives 4

1. The effectiveness of oral midazolam on compliance with treatment
2. The efficacy of oral midazolam on agitation and refusal of care
3. The safety of oral midazolam
4. Satisfaction among healthcare staff

Conditions and MedDRA coding

Neurocognitive Disorders and Agitation in Older Adults

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Men and women aged 60 and older
2. A patient hospitalized (for an estimated minimum of 21 days) in the Geriatric Department of Medical and Rehabilitation Care (SMR), Cognitive-Behavioral Unit (UCC), or residing in an Enhanced Care Unit (UHR), a Long-Term Care Unit (USLD), or a Psychogeriatric Unit (5UPG)
3. Moderate to severe cognitive impairment, defined by an MMSE (Mini-Mental State Examination) score <15. If this cannot be assessed at enrollment, an MMSE score <15 obtained within the past year
4. A patient who resists treatment, having experienced at least two episodes of resistance to treatment (excluding meals) for which other non-pharmacological alternatives have failed. These instances of resistance to treatment are defined by a “resistance to treatment” score of ≥3 on the Pittsburgh Scale over the past week
5. A person enrolled in Social Security or a similar program
6. Informed consent, in writing and signed by the patient or their legal representative (for adults subject to legal guardianship and unable to give consent, pursuant to Article L 1121-8 of the Public Health Code)

Exclusion criteria 17

1. Patients who received midazolam (regardless of the route of administration) within one week prior to enrollment
2. Patient with contraindications to midazolam: Myasthenia gravis
3. Patient with contraindications to midazolam: Severe respiratory failure requiring continuous oxygen therapy
4. Patients with contraindications to midazolam: Severe hepatic impairment: PT < 50%
5. Patient with contraindications to midazolam: Severe, untreated sleep apnea syndrome (based on available medical data: AHI [Apnea-Hypopnea Index] >30/h if polysomnography was performed)
6. Patients with contraindications to midazolam: Severe renal impairment: Cockcroft < 20 mL/min
7. Patients with contraindications to midazolam: Severe heart failure in a state of decompensation (NYHA clinical severity class 4 and/or in a state of acute decompensation)
8. Patient with contraindications to midazolam: History of alcoholism or substance abuse
9. Known hypersensitivity to the active ingredient, benzodiazepines, or any of the excipients
10. Patients also being treated with: CYP3A4 enzyme inhibitors or CYP3A4 enzyme inducers
11. Weight < 50 kg and > 100 kg
12. Gastrointestinal conditions that may limit or even prevent the absorption of midazolam (repeated vomiting, pancreatic insufficiency with steatorrhea, etc.; this list is not exhaustive: at the investigator’s discretion)
13. Identification of anxiety, as defined by Item E of the NPI (Neuropsychiatric Inventory), based on a score of >2 for both frequency and severity, in accordance with HAS recommendations
14. Identification of pain, defined by the Algoplus scale as a score of ≥ 2
15. Identification of delusional symptoms, as defined by item E of the Cornell Scale: E > 0 (if score = a: at the physician’s discretion, this will be documented in the patient’s medical record)
16. Subject currently excluded from another clinical trial
17. A person deprived of liberty by an administrative or judicial decision; Article L 1121-6 of the Code of Public Security

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A decrease of at least two points on the “resistance to treatment” subscale of the Pittsburgh Scale

Secondary endpoints 4

1. Care Acceptance Scale according to Rignell et al. (2007), measured at the end of care
2. Overall score on the Pittsburgh Agitation Scale, measured 30 to 45 minutes after administration of oral midazolam gel. This scale assesses four dimensions, rated on a scale of 0 to 4. Subscore for resistance to care
3. Measurement of oxygen saturation, respiratory rate, and heart rate, and recording of serious and non-serious adverse events occurring following administration of midazolam gel
4. Satisfaction survey on healthcare providers’ perception of patient well-being (unvalidated questionnaire developed specifically for the clinical trial), completed at the end of care

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Grenoble Alpes

Sponsor organisation

Centre Hospitalier Universitaire Grenoble Alpes

Address

Boulevard De La Chantourne, Cs 10217, La Tronche Cs 10217 La Tronche

City

Grenoble Cedex 9

Postcode

38043

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Grenoble Alpes

Contact name

GARNIER Virginie

Public contact point

Organisation

Centre Hospitalier Universitaire Grenoble Alpes

Contact name

GARNIER Virginie

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications