Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study)
Abstract Background Intranasal (i.n.) drug application is a widely known and low-invasive route of administration that may be able to achieve rapid symptom control in terminally ill patients. According to the German S3 guideline “Palliative care for patients with incurable cancer”, benzodiazepines,...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Palliative Care |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12904-023-01330-1 |
| _version_ | 1797362764813959168 |
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| author | Hanna Hirschinger Evelyn Jaeger Stefanie Nittka Svetlana Hetjens Christine Lorenz Constanze Remi Susanne Saussele Wolf-K. Hofmann Deniz Gencer Tobias Boch |
| author_facet | Hanna Hirschinger Evelyn Jaeger Stefanie Nittka Svetlana Hetjens Christine Lorenz Constanze Remi Susanne Saussele Wolf-K. Hofmann Deniz Gencer Tobias Boch |
| author_sort | Hanna Hirschinger |
| collection | DOAJ |
| description | Abstract Background Intranasal (i.n.) drug application is a widely known and low-invasive route of administration that may be able to achieve rapid symptom control in terminally ill patients. According to the German S3 guideline “Palliative care for patients with incurable cancer”, benzodiazepines, such as midazolam, are recommended for the treatment of terminal agitation. To the best of our knowledge there is no evidence for i.n. midazolam in terminally ill patients. We aim to assess the use of i.n. midazolam as an alternative to subcutaneous administration of the drug. Methods In this monocentric, randomised, controlled, open-label investigator initiated trial, n = 60 patients treated at the palliative care unit of a University Hospital will be treated with 5 mg midazolam i.n. versus 5 mg subcutaneous (s.c.) midazolam in the control arm when terminal agitation occurs (randomly assigned 1:1). The estimated recruitment period is 18 months. Treatment efficacy is defined as an improvement on the Richmond Agitation Sedation Scale (Palliative Version) (RASS-PAL) and a study specific numeric rating scale (NRS) before and after drug administration. Furthermore, plasma concentration determinations of midazolam will be conducted at t1 = 0 min, t2 = 5 min, and t3 = 20 min using liquid chromatography/mass spectrometry (LC-MS). The primary objective is to demonstrate non-inferiority of midazolam i.n. in comparison to midazolam s.c. for the treatment of agitation in terminally ill patients. Discussion Midazolam i.n. is expected to achieve at least equivalent reduction of terminal agitation compared to s.c. administration. In addition, plasma concentrations of midazolam i.n. are not expected to be lower than those of midazolam s.c. and the dynamics of the plasma concentration with an earlier increase could be beneficial. Trial registration German Clinical Trials Registry DRKS00026775, registered 07.07.2022, Eudra CT No.: 2021-004789-36. |
| first_indexed | 2024-03-08T16:11:11Z |
| format | Article |
| id | doaj.art-3ac82afd2aeb4788b503d915f9d4402b |
| institution | Directory Open Access Journal |
| issn | 1472-684X |
| language | English |
| last_indexed | 2024-03-08T16:11:11Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Palliative Care |
| spelling | doaj.art-3ac82afd2aeb4788b503d915f9d4402b2024-01-07T12:54:00ZengBMCBMC Palliative Care1472-684X2024-01-012311710.1186/s12904-023-01330-1Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study)Hanna Hirschinger0Evelyn Jaeger1Stefanie Nittka2Svetlana Hetjens3Christine Lorenz4Constanze Remi5Susanne Saussele6Wolf-K. Hofmann7Deniz Gencer8Tobias Boch93rd Department of Medicine, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg UniversityInstitute for Clinical Chemistry, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg UniversityInstitute for Clinical Chemistry, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg UniversityDepartment of Medical Statistics, Biomathematics and Information Processing, University Medical Center, Heidelberg UniversityPharmacy, Mannheim University HospitalHospital Pharmacy, Department of Palliative Medicine, LMU University Hospital, LMU Munich3rd Department of Medicine, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg University3rd Department of Medicine, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg UniversityCentre for Integrative Oncology, Pain and Palliative Medicine, Oeschelbronn Clinic3rd Department of Medicine, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg UniversityAbstract Background Intranasal (i.n.) drug application is a widely known and low-invasive route of administration that may be able to achieve rapid symptom control in terminally ill patients. According to the German S3 guideline “Palliative care for patients with incurable cancer”, benzodiazepines, such as midazolam, are recommended for the treatment of terminal agitation. To the best of our knowledge there is no evidence for i.n. midazolam in terminally ill patients. We aim to assess the use of i.n. midazolam as an alternative to subcutaneous administration of the drug. Methods In this monocentric, randomised, controlled, open-label investigator initiated trial, n = 60 patients treated at the palliative care unit of a University Hospital will be treated with 5 mg midazolam i.n. versus 5 mg subcutaneous (s.c.) midazolam in the control arm when terminal agitation occurs (randomly assigned 1:1). The estimated recruitment period is 18 months. Treatment efficacy is defined as an improvement on the Richmond Agitation Sedation Scale (Palliative Version) (RASS-PAL) and a study specific numeric rating scale (NRS) before and after drug administration. Furthermore, plasma concentration determinations of midazolam will be conducted at t1 = 0 min, t2 = 5 min, and t3 = 20 min using liquid chromatography/mass spectrometry (LC-MS). The primary objective is to demonstrate non-inferiority of midazolam i.n. in comparison to midazolam s.c. for the treatment of agitation in terminally ill patients. Discussion Midazolam i.n. is expected to achieve at least equivalent reduction of terminal agitation compared to s.c. administration. In addition, plasma concentrations of midazolam i.n. are not expected to be lower than those of midazolam s.c. and the dynamics of the plasma concentration with an earlier increase could be beneficial. Trial registration German Clinical Trials Registry DRKS00026775, registered 07.07.2022, Eudra CT No.: 2021-004789-36.https://doi.org/10.1186/s12904-023-01330-1Palliative careTerminal agitationMidazolamIntranasalNasal spray |
| spellingShingle | Hanna Hirschinger Evelyn Jaeger Stefanie Nittka Svetlana Hetjens Christine Lorenz Constanze Remi Susanne Saussele Wolf-K. Hofmann Deniz Gencer Tobias Boch Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study) BMC Palliative Care Palliative care Terminal agitation Midazolam Intranasal Nasal spray |
| title | Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study) |
| title_full | Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study) |
| title_fullStr | Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study) |
| title_full_unstemmed | Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study) |
| title_short | Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study) |
| title_sort | treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam study protocol for a randomised controlled open label monocentric trial mintu study |
| topic | Palliative care Terminal agitation Midazolam Intranasal Nasal spray |
| url | https://doi.org/10.1186/s12904-023-01330-1 |
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