Midazolam hydrochloride for Terminal illness requiring palliative care

Inclusion criteria

• {"criterion_text":"- Terminally ill patients with a life expectancy of less than one month.\n- Patients receiving palliative care in the palliative care ward at the study site\n- 18 years of age or older, at the time of signing the informed consent\n- Capable of giving signed informed consent as described in Appendix 1 at inclusion, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n- The attending physician finds the patient eligible for 1 mg of midazolam administered either SC or IV if symptoms commonly treated with parenteral midazolam, such as anxiety, restlessness, agitation, or insomnia, occur"}

Exclusion criteria

• {"criterion_text":"- Known hypersensitivity to midazolam other benzodiazepines, or any of the excipients listed in point 6.1 of the SmPC for midazolam 1 mg/ml (B. Braun) (sodium chloride, hydrochloric acid, or water for injections).\n- Strong indication for a dose of midazolam other than 1 mg, as judged by the attending physician\n- Clear indication for administration of either IV or SC injection (by consensus of two senior consultants in palliative medicine).\n- Received midazolam within the past 24 hours before study drug injection.\n- No development of symptoms requiring midazolam within 5 days from inclusion.\n- RASS PAL score of +3 or higher at the time of intervention, or if the next of kin, treating physician, or study personnel determine at that time that conducting serum measurements would pose a burden, even if consent has not been withdrawn.\n- Intake of strong CYP3A4 inducers/inhibitors, as defined by the FDA (U.S. Food and Drug Administration, 2023), within the last 7 days or during the 90-minute intervention period..\n- Hemoglobin < 9.0 g/dL.\n- Acute respiratory depression, defined as a respiratory rate < 8 breaths per minute at the time of intervention\n- Withdrawal of consent between inclusion and intervention, or at any other time\n- Inability to establish venous access for blood sampling and/or IV injection"}

Primary endpoints

• {"endpoint_text":"- AUC0-90 of midazolam based on serum samples collected at 2, 5, 7, 10, 12, 15, 20, 25, 30, 40, 50, 60, 75, and 90 minutes post-administration.","definition_or_measurement_approach":"AUC0-90 calculated from serum concentrations of midazolam measured from samples collected at 2, 5, 7, 10, 12, 15, 20, 25, 30, 40, 50, 60, 75 and 90 minutes post-dose."}

Secondary endpoints

• {"endpoint_text":"- Tmax, Cmax of midazolam and 1-OH-midazolam\n- AUC0-90 for 1-OH-midazolam\n- Metabolic ratio: AUC0-90 (1-OH-midazolam / midazolam).\n- Injection site discomfort (pain, redness, swelling, itching).\n- Change in respiratory rate from baseline at 10, 20, 30, 40, 50, 60, 75, and 90 minutes\n- Change in oxygen saturation from baseline at 10, 20, 30, 40, 50, 60, 75, and 90 minutes\n- Change in RASS-PAL score from baseline at 10, 20, 30, 40, 50, 60, 75, and 90 minutes\n- Time and number of repeated administrations of sedative medication within 90 minutes following study drug injection","definition_or_measurement_approach":"Tmax and Cmax determined from serum concentration–time profiles of midazolam and 1-OH-midazolam. AUC0-90 for 1-OH-midazolam calculated from serum samples collected up to 90 minutes. Metabolic ratio calculated as AUC0-90 (1-OH-midazolam / midazolam). Injection site discomfort assessed by recording pain, redness, swelling, itching. Respiratory rate, oxygen saturation and RASS-PAL score measured and compared to baseline at 10, 20, 30, 40, 50, 60, 75 and 90 minutes. Time and count of any repeated sedative administrations recorded within 90 minutes post-dose."}

Norway

Earliest CTIS Part Ii Submission Date

14-05-2025

Latest Decision Or Authorization Date

13-06-2025

Processing Time Days

30

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Akershus University Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway