Work

A randomized controlled clinical trial of intranasal versus subcutaneous midazolam for agitation in terminal illness (MinTU study)

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Background: Terminally ill patients often have difficulty taking medications. Suitable, minimally invasive, fast-acting administration routes are particularly important. Trials on alternative drug administration routes in palliative care are essential to base therapy decisions on evidence rather than experience. Aim: To evaluate the effectiveness of intranasal compared with subcutaneous midazolam for the initial management of terminal agitation in palliative care patients. Design: Randomized, investigator-initiated open-label phase-II trial, August 2022–July 2024. Setting/Participants: Monocentric trial at the palliative care ward of a German University Hospital. 180 patients were assessed for suitability, 60 patients (median age, 68 years (SD 12.3), 26 female) were randomized 1:1 and analyzed. Patients with terminal agitation fulfilling all eligibility criteria were randomized to midazolam 5 mg administered either intranasal ( n = 30) or subcutaneous ( n = 30). Primary outcome: Improvement of terminal agitation by midazolam administration assessed by RASS-PAL-score. Secondary outcome: Midazolam plasma concentrations after administration. Results: Median RASS-PAL-scores decreased significantly in both groups. Intranasal group: 2 at baseline, to –1 at 5 min and –2 at 20 min. Subcutaneous group: 1,–0 and –1. Within-group reductions exceeded the clinically relevant threshold of ⩾ 1 point at 5 and 20 min (all p < 0.0001). Median midazolam plasma concentrations were significantly higher intranasal (5 min: 90 ng/ml, 20 min: 83 ng/ml) than subcutaneous (5 min: 15 ng/ml, 20 min: 24 ng/ml). No patients withdrawn due to adverse effects. Conclusion: Midazolam intranasal administration was effective in reducing terminal agitation and achieves higher plasma concentrations compared to subcutaneous administration. It is an alternative route of application to improve end-of-life care for terminally ill patients. Trial Registration: MinTU Study 173-01, Eudra CT No.: 2021-004789-36, DRKS ID: 00026775 (07.07.2022, https://drks.de/search/de/trial/DRKS00026775 ).

Source: Palliative Medicine

DOI: 10.1177/02692163261428947