Midazolam Nasal Spray for Anxiety/Tension in Palliative Care – A Pilot Study
Résumé de l'étude
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)
Intervention étudiée
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)
Maladie en cours d'investigation
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)
Critères d'exclusion
- 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)
Lieu de l’étude
Bâle, Berne, Zurich
(BASEC)
Sponsor
Prof. Dr. med. Manuel Haschke representing Inselspital Universitättspital Bern
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Prof. Dr. med. Manuel Haschke
+41 31 63 2 67 93
manuel.haschke@clutterinsel.chKlinische Pharmakologie & Toxikologie Inselspital Universitätsspital Bern
(BASEC)
Informations générales
Inselspital, Universit?tsspital Bern,
+41 (0)31 632 67 93
manuel.haschke@clutterinsel.ch(ICTRP)
Informations scientifiques
Inselspital, Universit?tsspital Bern,
+41 (0)31 632 67 93
manuel.haschke@clutterinsel.ch(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale d'éthique de Berne
(BASEC)
Date d'approbation du comité d'éthique
13.09.2024
(BASEC)
Identifiant de l'essai ICTRP
NCT06330584 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
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)
Titre académique
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)
Titre public
Administration of Intranasal Midazolam for Anxiety in Palliative Care (ICTRP)
Maladie en cours d'investigation
Anxiety;Acute Anxiety;Palliative Care (ICTRP)
Intervention étudiée
Drug: Placebo Nasal Spray 0 mg/spray;Drug: Midazolam Nasal Spray 0.45 mg/spray;Drug: Midazolam Nasal Spray 0.9 mg/spray (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Critères d'inclusion/exclusion
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)
non disponible
Critères d'évaluation principaux et secondaires
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)
Date d'enregistrement
non disponible
Inclusion du premier participant
non disponible
Sponsors secondaires
University Hospital, Basel, Switzerland;University Hospital, Z?rich;Stadtspital Z?rich (ICTRP)
Contacts supplémentaires
Carla Meyer-Massetti, PhD;Manuel Haschke, MD, manuel.haschke@insel.ch, +41 (0)31 632 67 93, Inselspital, Universit?tsspital Bern, (ICTRP)
ID secondaires
2024-00873 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT06330584 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible