Administration of Intranasal Midazolam for Anxiety in Palliative Care

NCT06330584 | Recruiting Phase 2

• 1 other identifier: 2024-00873
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Anxiety; Acute Anxiety; Palliative Care

Keywords

Anxiety; Acute anxiety; Palliative Care; Midazolam; Nasal Spray

Outcome Measures

Primary Outcomes (1)

• 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.

  t [0 minutes, 30 minutes]

Secondary Outcomes (11)

• Sedation

  t [0 minutes, 30 minutes]

• Oxygen saturation SaO2 (percent %)

  t [0 minutes, 30 minutes]

• Heart rate (bpm)

  t [0 minutes, 30 minutes]

• Cortisol levels in oral fluid

  t [0 minutes, 30 minutes]

• Time to first requested additional dose

  t [starting assessment 30 minutes after intervention up to 24 hours after intervention]

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo Nasal Spray 0 mg/spray

Standard of Care (SOC)

ACTIVE COMPARATOR

Total dose of midazolam = 0.9 mg

Drug: Midazolam Nasal Spray 0.45 mg/spray

Double Dose of Standard of Care (2xSOC)

ACTIVE COMPARATOR

Total dose of midazolam = 1.8 mg

Drug: Midazolam Nasal Spray 0.9 mg/spray

Interventions

Placebo Nasal Spray 0 mg/spray 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

Placebo

Midazolam Nasal Spray 0.45 mg/spray 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

Standard of Care (SOC)

Midazolam Nasal Spray 0.9 mg/spray 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

Double Dose of Standard of Care (2xSOC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (5)

Palliativzentrum Bethesda Spital

Basel, Canton of Basel-City, 4052, Switzerland

RECRUITING

Inselspital, Universitätsspital Bern

Bern, 3010, Switzerland

NOT YET RECRUITING

Universitäres Zentrum für Palliative Care (UZP)

Bern, Switzerland

RECRUITING

Zentrum für Palliative Care, Stadtspital Zürich

Zurich, 8037, Switzerland

RECRUITING

Kompetenzzentrum Palliative Care, Universitätsspital Zürich

Zurich, 8091, Switzerland

RECRUITING

MeSH Terms

Conditions

Anxiety Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Study Officials

• Carla Meyer-Massetti, PhD

  Inselspital, Universitätsspital Bern

  STUDY CHAIR

Central Study Contacts

Manuel Haschke, MD

CONTACT

+41 (0)31 632 67 93; manuel.haschke@insel.ch

Ursina Wernli, MSc

CONTACT

ursina.wernli@students.unibe.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, randomized, placebo-controlled parallel-group multicenter exploratory pilot study with three study arms

Study Record Dates

• First Submitted: March 6, 2024
• First Posted: March 26, 2024
• Study Start: December 20, 2024
• Primary Completion: September 1, 2025
• Study Completion: October 1, 2025
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (5)