Midazolam Nasal Spray for Anxiety/Tension in Palliative Care – A Pilot Study
Zusammenfassung der Studie
Anxiety is a common and highly distressing symptom in patients receiving palliative care, affecting quality of life. Midazolam is an active substance commonly used to treat acute anxiety/tension. However, oral administration in palliative care patients is often limited. Therefore, alternative routes of administration are used, which are not officially approved in Switzerland and are poorly studied, including Midazolam Nasal Spray (MNS). The dose of MNS for treating acute anxiety states/tension in palliative care is much lower compared to doses administered for other symptoms (e.g., seizures), but there is a lack of data on safety and efficacy. This study aims to fill an important knowledge gap and investigate how different doses of MNS can help with anxiety and whether they are safe. The Inselspital Bern, the University Hospital Zurich, and the City Hospital Zurich will participate in the study and enroll 36 patients over a period of 6 months. The study is expected to run from July to December 2024.
(BASEC)
Untersuchte Intervention
One patient group receives a standard dose of the medication, another receives a higher dose, and the third group receives a placebo (no active substance). The study will be conducted double-blind, meaning that neither patients nor doctors know who receives which dose. Before and 30 minutes after the administration of MNS, encrypted data on the extent of patients' anxiety/tension, blood oxygen levels, heart rate, and drowsiness will be collected.
To better understand how midazolam is absorbed, metabolized, and excreted by the body, the study will also examine the blood levels of the study medication in some patients who already have a venous access.
(BASEC)
Untersuchte Krankheit(en)
Acute Anxiety/Tension in Palliative Care
(BASEC)
- Adult patients from the participating palliative care units - Acute anxiety (reported by patients) with medical justification for midazolam nasal spray for symptom relief - Ability and willingness to provide written consent/presence of written consent - Ability and willingness to conduct anxiety assessment - Additionally, for patients included in the blood analysis: presence of any type of venous access to facilitate blood sample collection and avoid a puncture/placement of a venous access (BASEC)
Ausschlusskriterien
- Midazolam nasal spray prescribed for epileptic seizures or for continuous pharmacological sedation - Allergy/hypersensitivity to midazolam or paradoxical reaction in medical history - Impaired absorption of active substances at the nasal septum - Receipt of midazolam nasal spray within 24 hours prior to study inclusion - Time between informed consent and study inclusion less than 24 hours - Concomitant medication with strong CYP3A4-influencing substances (CYP3A4 is an enzyme that is significantly involved in the metabolism of midazolam and other substances) or with substances that have a depressant effect on the central nervous system - Recently started therapy with strong opioids in the last 5 days - Acute angle-closure glaucoma - Inability to follow study procedures or to provide informed consent (BASEC)
Studienstandort
Basel, Bern, Zürich
(BASEC)
Sponsor
Prof. Dr. med. Manuel Haschke representing Inselspital Universitättspital Bern
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Prof. Dr. med. Manuel Haschke
+41 31 63 2 67 93
manuel.haschke@clutterinsel.chKlinische Pharmakologie & Toxikologie Inselspital Universitätsspital Bern
(BASEC)
Allgemeine Auskünfte
Inselspital, Universit?tsspital Bern,
+41 (0)31 632 67 93
manuel.haschke@clutterinsel.ch(ICTRP)
Wissenschaftliche Auskünfte
Inselspital, Universit?tsspital Bern,
+41 (0)31 632 67 93
manuel.haschke@clutterinsel.ch(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Bern
(BASEC)
Datum der Bewilligung durch die Ethikkommission
13.09.2024
(BASEC)
ICTRP Studien-ID
NCT06330584 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
Administration of intranasal midazolam for anxiety in palliative care – a double-blind, randomized, placebo- controlled multicenter exploratory pilot study with a nested pharmacokinetic analysis (AIM Care) (BASEC)
Wissenschaftlicher Titel
Administration of Intranasal Midazolam for Anxiety in Palliative Care - a Double-blind, Randomized, Placebo-controlled Multicenter Exploratory Pilot Study With a Nested Pharmacokinetic Analysis (ICTRP)
Öffentlicher Titel
Administration of Intranasal Midazolam for Anxiety in Palliative Care (ICTRP)
Untersuchte Krankheit(en)
Anxiety;Acute Anxiety;Palliative Care (ICTRP)
Untersuchte Intervention
Drug: Placebo Nasal Spray 0 mg/spray;Drug: Midazolam Nasal Spray 0.45 mg/spray;Drug: Midazolam Nasal Spray 0.9 mg/spray (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
Gender: All
Maximum age: N/A
Minimum age: 18 Years
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) (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Change from baseline in anxiety levels, measured by Visual Analogue Scale (VAS) and quantified by Numerical Rating Scale (NRS) (ICTRP)
Sedation;Oxygen saturation SaO2 (percent %);Heart rate (bpm);Cortisol levels in oral fluid;Time to first requested additional dose;Cumulative number of doses over 24 hours;Number of patients with adverse drug events (ADEs);Peak plasma concentration (Cmax);Time to reach the peak plasma concentration (Tmax);Elimination half-life (t1/2);Area under the curve (AUC0-?, AUC0-8) (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
University Hospital, Basel, Switzerland;University Hospital, Z?rich;Stadtspital Z?rich (ICTRP)
Weitere Kontakte
Carla Meyer-Massetti, PhD;Manuel Haschke, MD, manuel.haschke@insel.ch, +41 (0)31 632 67 93, Inselspital, Universit?tsspital Bern, (ICTRP)
Sekundäre IDs
2024-00873 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT06330584 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar