Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility study

Abstract Background Intravenous (IV) vasopressors are the mainstay of physiological support for hemodynamically unstable patients. However, the role of oral vasopressors remains unclear. The objective of our study was to evaluate the feasibility of evaluating midodrine for critically ill patients wi...

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Main Authors: Sebastian J. Kilcommons, Fadi Hammal, Dawn L. Opgenorth, Kirsten M. Fiest, Constantine J. Karvellas, Vincent I. Lau, Erika MacIntyre, Janek Senaratne, Jocelyn Slemko, Wendy Sligl, Fernando Zampieri, D.’Arcy Duquette, Lily T. Guan, Nadia Baig, Sean M. Bagshaw, Oleksa G. Rewa
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Pilot and Feasibility Studies
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Online Access:https://doi.org/10.1186/s40814-024-01577-2
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author Sebastian J. Kilcommons
Fadi Hammal
Dawn L. Opgenorth
Kirsten M. Fiest
Constantine J. Karvellas
Vincent I. Lau
Erika MacIntyre
Janek Senaratne
Jocelyn Slemko
Wendy Sligl
Fernando Zampieri
D.’Arcy Duquette
Lily T. Guan
Nadia Baig
Sean M. Bagshaw
Oleksa G. Rewa
author_facet Sebastian J. Kilcommons
Fadi Hammal
Dawn L. Opgenorth
Kirsten M. Fiest
Constantine J. Karvellas
Vincent I. Lau
Erika MacIntyre
Janek Senaratne
Jocelyn Slemko
Wendy Sligl
Fernando Zampieri
D.’Arcy Duquette
Lily T. Guan
Nadia Baig
Sean M. Bagshaw
Oleksa G. Rewa
author_sort Sebastian J. Kilcommons
collection DOAJ
description Abstract Background Intravenous (IV) vasopressors are the mainstay of physiological support for hemodynamically unstable patients. However, the role of oral vasopressors remains unclear. The objective of our study was to evaluate the feasibility of evaluating midodrine for critically ill patients with IV vasopressor-dependent shock. Methods We conducted a single-center, concealed-allocation, parallel-group, blinded feasibility randomized controlled trial (RCT) evaluating the effect of oral midodrine versus placebo on IV vasopressor-dependent shock in the intensive care unit (ICU). The study was performed in a medical-surgical ICU at the University of Alberta Hospital from April 2021 to July 2022. We included patients aged 18 years or older admitted to the ICU with ongoing vasopressor support with decreasing vasopressor dose(s). Patients were randomly assigned 1:1 to midodrine or a placebo for the duration of their IV vasopressor therapy. The primary outcome was study feasibility and secondary outcomes included patient-centered outcomes. Feasibility was assessed through rate of recruitment, adherence to study protocol, and patient safety. Results Twenty patients were enrolled in the study and underwent randomization (n = 11 midodrine, n = 9 control). Recruitment was recorded at 1.2 participants per month, protocol adherence was 90%, and allocation remained concealed. No adverse events were reported in either group. Sepsis was the most common cause of shock in both groups. The midodrine group had a shorter length of ICU stay of 9.6 (SD 8.7) vs 10.4 (SD 14.5) days. Hospital mortality was lower for the midodrine group (n = 2, 18.2% vs n = 4, 37.5%). Vasopressor re-initiation after 24 h was more frequent in the midodrine group (n = 4, 36.4% vs n = 2, 25%). There were no readmissions to the ICU following discharge in either group. Conclusions The evaluation of midodrine for patients in the ICU is feasible and safe. This trial will inform future large-scale RCTs regarding the utility of midodrine in critically ill patients with IV vasopressor-dependent shock. Trial registration This pilot RCT was registered at clinicaltrials.gov (NCT04489589). Registered July 27, 2020. https://clinicaltrials.gov/study/NCT04489589
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spelling doaj-art-011f21a98ec14aa78d5df8cb59c14b672025-08-20T02:20:45ZengBMCPilot and Feasibility Studies2055-57842024-12-011011910.1186/s40814-024-01577-2Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility studySebastian J. Kilcommons0Fadi Hammal1Dawn L. Opgenorth2Kirsten M. Fiest3Constantine J. Karvellas4Vincent I. Lau5Erika MacIntyre6Janek Senaratne7Jocelyn Slemko8Wendy Sligl9Fernando Zampieri10D.’Arcy Duquette11Lily T. Guan12Nadia Baig13Sean M. Bagshaw14Oleksa G. Rewa15University of AlbertaUniversity of AlbertaUniversity of AlbertaDepartment of Critical Care Medicine, University of CalgaryUniversity of AlbertaUniversity of AlbertaUniversity of AlbertaUniversity of AlbertaUniversity of AlbertaUniversity of AlbertaUniversity of AlbertaDepartment of Critical Care Medicine, University of CalgaryUniversity of AlbertaUniversity of AlbertaUniversity of AlbertaUniversity of AlbertaAbstract Background Intravenous (IV) vasopressors are the mainstay of physiological support for hemodynamically unstable patients. However, the role of oral vasopressors remains unclear. The objective of our study was to evaluate the feasibility of evaluating midodrine for critically ill patients with IV vasopressor-dependent shock. Methods We conducted a single-center, concealed-allocation, parallel-group, blinded feasibility randomized controlled trial (RCT) evaluating the effect of oral midodrine versus placebo on IV vasopressor-dependent shock in the intensive care unit (ICU). The study was performed in a medical-surgical ICU at the University of Alberta Hospital from April 2021 to July 2022. We included patients aged 18 years or older admitted to the ICU with ongoing vasopressor support with decreasing vasopressor dose(s). Patients were randomly assigned 1:1 to midodrine or a placebo for the duration of their IV vasopressor therapy. The primary outcome was study feasibility and secondary outcomes included patient-centered outcomes. Feasibility was assessed through rate of recruitment, adherence to study protocol, and patient safety. Results Twenty patients were enrolled in the study and underwent randomization (n = 11 midodrine, n = 9 control). Recruitment was recorded at 1.2 participants per month, protocol adherence was 90%, and allocation remained concealed. No adverse events were reported in either group. Sepsis was the most common cause of shock in both groups. The midodrine group had a shorter length of ICU stay of 9.6 (SD 8.7) vs 10.4 (SD 14.5) days. Hospital mortality was lower for the midodrine group (n = 2, 18.2% vs n = 4, 37.5%). Vasopressor re-initiation after 24 h was more frequent in the midodrine group (n = 4, 36.4% vs n = 2, 25%). There were no readmissions to the ICU following discharge in either group. Conclusions The evaluation of midodrine for patients in the ICU is feasible and safe. This trial will inform future large-scale RCTs regarding the utility of midodrine in critically ill patients with IV vasopressor-dependent shock. Trial registration This pilot RCT was registered at clinicaltrials.gov (NCT04489589). Registered July 27, 2020. https://clinicaltrials.gov/study/NCT04489589https://doi.org/10.1186/s40814-024-01577-2Intensive care unitCritical careShockVasopressorsMidodrine
spellingShingle Sebastian J. Kilcommons
Fadi Hammal
Dawn L. Opgenorth
Kirsten M. Fiest
Constantine J. Karvellas
Vincent I. Lau
Erika MacIntyre
Janek Senaratne
Jocelyn Slemko
Wendy Sligl
Fernando Zampieri
D.’Arcy Duquette
Lily T. Guan
Nadia Baig
Sean M. Bagshaw
Oleksa G. Rewa
Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility study
Pilot and Feasibility Studies
Intensive care unit
Critical care
Shock
Vasopressors
Midodrine
title Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility study
title_full Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility study
title_fullStr Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility study
title_full_unstemmed Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility study
title_short Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): a feasibility study
title_sort midodrine for the early liberation from vasopressor support in the icu liberate a feasibility study
topic Intensive care unit
Critical care
Shock
Vasopressors
Midodrine
url https://doi.org/10.1186/s40814-024-01577-2
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