Administration of Intranasal Midazolam for Anxiety in Palliative Care
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Placebo Nasal Spray 0 mg/spray, Midazolam Nasal Spray 0.45 mg/spray, Midazolam Nasal Spray 0.9 mg/spray.
- Who it may be relevant to
- Registry conditions: Anxiety, Acute Anxiety, Palliative Care. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Switzerland
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Administration of Intranasal Midazolam for Anxiety in Palliative Care - a Double-blind, Randomized, Placebo-controlled Multicenter Exploratory Pilot Study With a Nested Pharmacokinetic Analysis
Overview
The goal of this double-blind, randomized, placebo-controlled parallel-group multicenter exploratory pilot study (three study arms) is to describe effects and safety of different doses of intranasal midazolam to treat acute anxiety in palliative care patients, while providing pharmacokinetic and pharmacodynamic data.
Detailed description
36 patients (12 per study arm) will be enrolled. All patients hospitalized at the four study sites, which are prescribed intranasal midazolam in their as-needed drug regimen and who meet inclusion criteria, are eligible. Patients will be asked for consent at the time of prescription of midazolam by the attending physician. Patients who have provided consent and have been randomized to one of the arms will be included (block randomization).
In a nested analysis, pharmacokinetic properties of all three doses will be analyzed in participants with available venous access.
The primary outcome is the change in patient-reported levels of anxiety from baseline. Secondary outcomes include time until first requested additional dose, cumulative number of doses including time points of administration after the first application, oxygen saturation, heart rate, cortisol levels in oral fluid, levels of sedation on the Richmond Agitation Sedation Scale Palliative Version (RASS-PAL), and occurrence of (serious) adverse events.
The primary and secondary outcomes will be assessed at baseline, i.e., immediately before the intervention (0 minutes) and 30 minutes after the intervention. The secondary outcomes 'Time to first requested additional dose' and 'Cumulative number of doses over 24 hours' as well as (serious) adverse events will be assessed starting 30 minutes after the intervention up to 24 hours after the intervention.
In patients included in the nested pharmacokinetic analysis, basic pharmacokinetic parameters will additionally be assessed at 10 time points, starting at baseline (0 minutes) up to 240 minutes after the intervention.
Interventions
- Drug Placebo Nasal Spray 0 mg/spray
A unit-dose nasal spray will be used for the intervention. 1 spray (= 0.1 μl = 0 mg midazolam/spray) in each nostril, i.e., no active compound - Drug Midazolam Nasal Spray 0.45 mg/spray
A unit-dose nasal spray will be used for the intervention. 1 spray (= 0.1 μl = 0.45 mg midazolam/spray) in each nostril, i.e., total dose of midazolam 0.9 mg - Drug Midazolam Nasal Spray 0.9 mg/spray
A unit-dose nasal spray will be used for the intervention. 1 spray (= 0.1 μl = 0.9 mg midazolam/spray) in each nostril, i.e., total dose of midazolam 1.8 mg
Primary outcome measures
- Change from baseline in anxiety levels, measured by Visual Analogue Scale (VAS) and quantified by Numerical Rating Scale (NRS) [Time frame: t [0 minutes, 30 minutes]]
Secondary outcome measures (11)
- Sedation [Time frame: t [0 minutes, 30 minutes]]
- Oxygen saturation SaO2 (percent %) [Time frame: t [0 minutes, 30 minutes]]
- Heart rate (bpm) [Time frame: t [0 minutes, 30 minutes]]
- Cortisol levels in oral fluid [Time frame: t [0 minutes, 30 minutes]]
- Time to first requested additional dose [Time frame: t [starting assessment 30 minutes after intervention up to 24 hours after intervention]]
- Cumulative number of doses over 24 hours [Time frame: t [starting assessment 30 minutes after intervention up to 24 hours after intervention]]
- Number of patients with adverse drug events (ADEs) [Time frame: t [starting immediately after intervention up to 24 hours after intervention]]
- Peak plasma concentration (Cmax) [Time frame: t [0 minutes up to 240 minutes after intervention]]
- Time to reach the peak plasma concentration (Tmax) [Time frame: t [0 minutes up to 240 minutes after intervention]]
- Elimination half-life (t1/2) [Time frame: t [0 minutes up to 240 minutes after intervention]]
- Area under the curve (AUC0-Τ, AUC0-∞) [Time frame: t [0 minutes up to 240 minutes after intervention]]
Eligibility criteria
Inclusion criteria
- Adult palliative care patients (≥ 18 years) hospitalized at one of the study sites
- Self-reported acute anxiety with clinical indication for intranasal midazolam administration according to attending physician
- Patient willing and able to provide written informed consent
- Informed consent as documented by signature
- Patient willing and able to complete anxiety assessment
- Additionally for nested pharmacokinetic analysis: Patients with available central or peripheral venous access, i.e., peripheral venous catheter (PVC), central venous catheter (CVC), peripherally inserted central venous catheter (PICC) line, midline catheter, or PORT-A-CATH® (PAC), and patient willing and able to provide blood samples
Exclusion criteria
- Intranasal midazolam prescribed for seizures
- Midazolam (any route of administration) prescribed and administered for continuous sedation
- History of allergy or hypersensitivity to midazolam
- History of benzodiazepine-related paradoxical reaction to midazolam
- Acute narrow-angle glaucoma
- Impaired nasal absorption (e.g., nasogastric tube, nasal obstruction, nasal polyps, etc.)
- Intranasal midazolam within 24 h before study enrollment
- Time between informed general consent for study participation through investigators and planned midazolam administration < 24 h
- Co-medication with strong CYP3A4 inducers or inhibitors according to pre-defined list (FDA)
- Recently initiated therapy with strong opioids (i.e., within past 5 days)
- Co-medication with other CNS depressants causing clinically relevant degree of sedation
- Inability to follow the procedures of the study (i.e., provision of Informed Consent, completion of assessment tool, e.g., due to language problems or dementia)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
Switzerland · 5 centers
- Palliativzentrum Bethesda Spital — Basel
- Inselspital, Universitätsspital Bern — Bern
- Universitäres Zentrum für Palliative Care (UZP) — Bern
- Zentrum für Palliative Care, Stadtspital Zürich — Zurich
- Kompetenzzentrum Palliative Care, Universitätsspital Zürich — Zurich
Identifiers
NCT: NCT06330584 · 2024-00873