AnxietyPhase 2AIM CareNCT06330584
Administration of Intranasal Midazolam for Anxiety in Palliative Care
A Phase 2 study testing Midazolam Nasal Spray 0.45 mg/spray and Midazolam Nasal Spray 0.9 mg/spray in people with Anxiety and Acute Anxiety, run by Insel Gruppe AG, University Hospital Bern at 5 sites in Switzerland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anxiety, Acute Anxiety, Palliative Care
- What is being tested?
- Midazolam Nasal Spray 0.45 mg/spray and Midazolam Nasal Spray 0.9 mg/spray
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 5 sitesSwitzerland
- Study dates
- 20 Dec 2024to Oct 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.)
Show all 12Show fewer
- 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)
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Ursina Wernli, MSc contact
5 sites in 1 country
Switzerland5 sites, 5 recruiting
- Recruiting
Palliativzentrum Bethesda Spital
Basel, Canton of Basel-City, 4052
Jan Gärtner, MD, +41 61 315 20 19, jan.gaerter@bethesda-spital.ch
- Not yet recruiting
Inselspital, Universitätsspital Bern
Bern, 3010
Manuel Haschke, MD, +41 (0)31 632 67 93, manuel.haschke@insel.ch
Manuel Haschke
- Recruiting
Universitäres Zentrum für Palliative Care (UZP)
Bern
Steffen Eychmüller, MD, +41 (0)31 632 51 07, steffen.eychmueller@insel.ch
- Recruiting
Zentrum für Palliative Care, Stadtspital Zürich
Zurich, 8037
Andreas Major, MD, +41 (0)44 417 29 26, andreas.major@stadtspital.ch
- Recruiting
Kompetenzzentrum Palliative Care, Universitätsspital Zürich
Zurich, 8091
Caroline Hertler, MD, +41 (0)44 255 29 34, caroline.hertler@usz.ch
About this study
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
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.
Read the 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.
- Conditions
- Anxiety, Acute Anxiety, Palliative Care
- Being tested
- Placebo Nasal Spray 0 mg/spray, Midazolam Nasal Spray 0.45 mg/spray, Midazolam Nasal Spray 0.9 mg/spray
- Keywords
- Anxiety, Acute anxiety, Palliative Care, Midazolam, Nasal Spray
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo Nasal Spray 0 mg/sprayDrug
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
Midazolam Nasal Spray 0.45 mg/sprayDrug
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
Midazolam Nasal Spray 0.9 mg/sprayDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Total dose of midazolam = 0 mg (no active compound) Receives: Drug: Placebo Nasal Spray 0 mg/spray |
| Standard of Care (SOC) | Active comparator | Total dose of midazolam = 0.9 mg Receives: Drug: Midazolam Nasal Spray 0.45 mg/spray |
| Double Dose of Standard of Care (2xSOC) | Active comparator | Total dose of midazolam = 1.8 mg Receives: Drug: Midazolam Nasal Spray 0.9 mg/spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in anxiety levels, measured by Visual Analogue Scale (VAS) and quantified by Numerical Rating Scale (NRS)
Patient-reported levels of anxiety, measured by VAS (0-100 mm, from left 'no anxiety at all' to right 'worst possible anxiety') at baseline (0 minutes) and 30 minutes after study drug or placebo administration. The VAS response will be quantified measuring the distance in mm from zero to the position of the VAS response on a ruler (=100 mm, separated by 1 mm intervals), with 0 mm representing absence of anxiety, and 100 mm representing maximal possible anxiety.
Measured: t [0 minutes, 30 minutes]
Secondary outcomes (11)
Sedation
Richmond Agitation Sedation Scale Palliative Version (RASS-PAL)
The RASS-PAL ranges from +4 (combative) to -5 (not rousable), where a higher score (below 0) is associated with agitation and a lower score (below 0) is associated with sedation. A score of 0 (alert and calm) is considered the most balanced state.
Measured: t [0 minutes, 30 minutes]
Oxygen saturation SaO2 (percent %)
Oxygen saturation
Measured: t [0 minutes, 30 minutes]
Heart rate (bpm)
Measured: t [0 minutes, 30 minutes]
Cortisol levels in oral fluid
Measured: t [0 minutes, 30 minutes]
Time to first requested additional dose
30 minutes after the intervention, additional doses may be administered as-needed. The time point until the first additional dose starting 30 minutes after the intervention is assessed. The time point can occur anywhere between 30 minutes and 24 hours after the intervention.
Measured: t [starting assessment 30 minutes after intervention up to 24 hours after intervention]
Cumulative number of doses over 24 hours
As additional doses may be administered after 30 minutes after the intervention, every additional requested dose is assessed and the total number of doses over 24 hours after the intervention is calculated.
Measured: t [starting assessment 30 minutes after intervention up to 24 hours after intervention]
Number of patients with adverse drug events (ADEs)
The adverse drug reactions (ADRs, i.e. reactions to be expected from the intervention based on clinical experience and the SmPC of Nayzilam), and (serious) adverse events ((S)AEs) will be assessed at three different time windows: between study drug administration and 30 minutes after the intervention, 30 minutes after study drug administration, and up to 24 hours after the intervention.
Measured: t [starting immediately after intervention up to 24 hours after intervention]
Peak plasma concentration (Cmax)
Pharmacokinetic parameter obtained by non-compartmental analysis (NCA) or compartmental analysis (CA) in a pre-defined eligible subset of patients (i.e., patients with a central or peripheral venous access).
There will be 10 measurement points: at baseline (0 minutes, i.e., before intervention) and at t [2.5, 5, 10, 15, 30, 60, 120, 180, 240 minutes].
Measured: t [0 minutes up to 240 minutes after intervention]
Time to reach the peak plasma concentration (Tmax)
Pharmacokinetic parameter obtained by non-compartmental analysis (NCA) or compartmental analysis (CA) in a pre-defined eligible subset of patients (i.e., patients with a central or peripheral venous access).
There will be 10 measurement points: at baseline (0 minutes, i.e., before intervention) and at t [2.5, 5, 10, 15, 30, 60, 120, 180, 240 minutes].
Measured: t [0 minutes up to 240 minutes after intervention]
Elimination half-life (t1/2)
Pharmacokinetic parameter obtained by non-compartmental analysis (NCA) or compartmental analysis (CA) in a pre-defined eligible subset of patients (i.e., patients with a central or peripheral venous access).
There will be 10 measurement points: at baseline (0 minutes, i.e., before intervention) and at t [2.5, 5, 10, 15, 30, 60, 120, 180, 240 minutes].
Measured: t [0 minutes up to 240 minutes after intervention]
Area under the curve (AUC0-Τ, AUC0-∞)
Pharmacokinetic parameter obtained by non-compartmental analysis (NCA) or compartmental analysis (CA) in a pre-defined eligible subset of patients (i.e., patients with a central or peripheral venous access).
There will be 10 measurement points: at baseline (0 minutes, i.e., before intervention) and at t [2.5, 5, 10, 15, 30, 60, 120, 180, 240 minutes].
Measured: t [0 minutes up to 240 minutes after intervention]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2024
- Study start20 Dec 2024
- Primary completionSep 2025 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnxietyStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, randomized, placebo-controlled parallel-group multicenter exploratory pilot study with three study arms
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carla Meyer-Massetti, PhD, Study chair, Inselspital, Universitätsspital Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06330584
- Sponsor's protocol ID
- 2024-00873
- Acronym
- AIM Care
- Status last verified
- Sep 2025
- First submitted
- 6 Mar 2024
- Last updated
- 10 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06330584
- Acronym / sponsor ID
- AIM Care / 2024-00873
- Conditions
- Anxiety, Acute Anxiety, Palliative Care
- Keywords
- Anxiety, Acute anxiety, Palliative Care, Midazolam, Nasal Spray
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 20 Dec 2024 (actual)
- Primary completion
- Sep 2025 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 26 Mar 2024 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Double-blind, randomized, placebo-controlled parallel-group multicenter exploratory pilot study with three study arms
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo Nasal Spray 0 mg/sprayTotal dose of midazolam = 0 mg (no active compound) |
| Standard of Care (SOC) | Active comparator | Drug: Midazolam Nasal Spray 0.45 mg/sprayTotal dose of midazolam = 0.9 mg |
| Double Dose of Standard of Care (2xSOC) | Active comparator | Drug: Midazolam Nasal Spray 0.9 mg/sprayTotal dose of midazolam = 1.8 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| Placebo Nasal Spray 0 mg/sprayA 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 | Placebo |
| Midazolam Nasal Spray 0.45 mg/sprayA 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 | Standard of Care (SOC) |
| Midazolam Nasal Spray 0.9 mg/sprayA 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 | Drug | Double Dose of Standard of Care (2xSOC) |
Primary outcome
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]
Patient-reported levels of anxiety, measured by VAS (0-100 mm, from left 'no anxiety at all' to right 'worst possible anxiety') at baseline (0 minutes) and 30 minutes after study drug or placebo administration. The VAS response will be quantified measuring the distance in mm from zero to the position of the VAS response on a ruler (=100 mm, separated by 1 mm intervals), with 0 mm representing absence of anxiety, and 100 mm representing maximal possible anxiety.
11 secondary outcomes
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]
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2025.
- 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.
Ursina Wernli, MSc contact
Carla Meyer-Massetti, PhD study chair
Inselspital, Universitätsspital Bern
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Midazolam Nasal Spray 0.45 mg/spray and Midazolam Nasal Spray 0.9 mg/spray in people with Anxiety and Acute Anxiety, run by Insel Gruppe AG, University Hospital Bern at 5 sites in Switzerland.
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 6 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 10 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Switzerland. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Manuel Haschke, MD (+41 (0)31 632 67 93, manuel.haschke@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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]). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Sep 2025.