Administration of Intranasal Midazolam for Anxiety in Palliative Care

NCT ID: NCT06330584

Last Updated: 2025-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-20

Study Completion Date

2025-10-31

Brief Summary

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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

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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

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Anxiety Acute Anxiety Palliative Care

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double-blind, randomized, placebo-controlled parallel-group multicenter exploratory pilot study with three study arms
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
All study personnel except the personnel at the facility preparing the investigational medicinal product (IMP) (Hospital Pharmacy, University Hospital Basel), and all patients will be blinded to the assigned treatment. Allocation will be concealed using sequentially coded drug packs (using consecutive patient identification numbers from 1 to 36) containing the IMP that are otherwise identical. Each drug pack will contain two nasal sprays of identical appearance. Patients and all trial personnel involved in recruitment and care of patients, trial assessment, monitoring, and analyses will be blinded to the assigned trial arm. Blinding will be upheld until the last patient (36 patients, i.e., 12 per study arm) has completed the pilot study and data entry into the trial database has been completed.

To safeguard blinding, placebo formulation will be produced with the same pH as the active study drug formulations to mimic nasal irritation induced by verum sprays.

Study Groups

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Placebo

Total dose of midazolam = 0 mg (no active compound)

Group Type PLACEBO_COMPARATOR

Placebo Nasal Spray 0 mg/spray

Intervention Type DRUG

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

Standard of Care (SOC)

Total dose of midazolam = 0.9 mg

Group Type ACTIVE_COMPARATOR

Midazolam Nasal Spray 0.45 mg/spray

Intervention Type DRUG

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

Double Dose of Standard of Care (2xSOC)

Total dose of midazolam = 1.8 mg

Group Type ACTIVE_COMPARATOR

Midazolam Nasal Spray 0.9 mg/spray

Intervention Type DRUG

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

Interventions

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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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Carla Meyer-Massetti, PhD

Role: STUDY_CHAIR

Inselspital, Universitätsspital Bern

Locations

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Palliativzentrum Bethesda Spital

Basel, Canton of Basel-City, Switzerland

Site Status RECRUITING

Inselspital, Universitätsspital Bern

Bern, , Switzerland

Site Status NOT_YET_RECRUITING

Universitäres Zentrum für Palliative Care (UZP)

Bern, , Switzerland

Site Status RECRUITING

Zentrum für Palliative Care, Stadtspital Zürich

Zurich, , Switzerland

Site Status RECRUITING

Kompetenzzentrum Palliative Care, Universitätsspital Zürich

Zurich, , Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Manuel Haschke, MD

Role: CONTACT

+41 (0)31 632 67 93

Ursina Wernli, MSc

Role: CONTACT

Facility Contacts

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Jan Gärtner, MD

Role: primary

+41 61 315 20 19

Manuel Haschke, MD

Role: primary

+41 (0)31 632 67 93

Steffen Eychmüller, MD

Role: primary

+41 (0)31 632 51 07

Andreas Major, MD

Role: primary

+41 (0)44 417 29 26

Caroline Hertler, MD

Role: primary

+41 (0)44 255 29 34

Other Identifiers

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2024-00873

Identifier Type: -

Identifier Source: org_study_id

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