A pilot, feasibility, randomised controlled trial of midodrine as adjunctive vasopressor for low-dose vasopressor-dependent hypotension in intensive care patients: The MAVERIC study

Costa-Pinto, Rahul; Yong, Zhen-Ti; Yanase, Fumitaka; Young, Chelsea; Brown, Alastair; Udy, Andrew; Young, Paul; Eastwood, Glenn M; Bellomo, Rinaldo

doi:10.1016/j.jcrc.2021.11.004

Cited by 17 publications

(36 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 18 Finally, the MAVERIC study, a pilot open-label RCT of 62 patients on low-dose intravenous vasopressor therapy, determined that adjunctive midodrine, while safe to use, was not associated with any physiological or clinical efficacy. 19 While previous systematic reviews have included the MIDAS study, there has been no review or meta-analysis conducted to date that has included the most recently published RCTs. Further, previous studies have not included any a priori subgroup analysis and our review will be evaluating the use of midodrine specifically in patients with known cirrhosis as well as with AKI.…”

Section: Discussionmentioning

confidence: 99%

“…Further, more recently published randomised controlled trials (RCTs) have found results that conflict with the MIDAS trial, further questioning the role of midodrine for vasopressor dependent hypotension. [17][18][19] While a recently published meta-analysis examining the role of midodrine in resolving shock did not find any difference in intravenous vasopressor duration, ICU or hospital lengths of stay or mortality, the review did not provide any subgroup analysis or use Grading of Recommendations, Assessment, Development and Evaluations (GRADE) recommendations or trial sequential analysis (TSA) methods. 20 Further, it was conducted prior to the publication of most recent evidence.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

“…Recently, there have been several RCTs that have evaluated the use of midodrine as an adjunctive therapy to intravenous vasopressor dependent hypotension. [16][17][18][19] The MIDAS trial randomised 136 undifferentiated hypotensive patients to either midodrine or placebo evaluating the median time from study drug initiation until discontinuation of intravenous vasopressors. The study investigators determined that there was no significant difference between groups.…”

Section: Subgroup Analysesmentioning

confidence: 99%

“…16 More recently, there have been smaller published RCTs that have shown conflicting results. [17][18][19] Adly et al evaluated the use of midodrine in 60 patients with septic shock and clinical stability on low-dose intravenous vasopressors for at least 24 hours and determined that midodrine was associated with significantly shortened duration of intravenous vasopressor support and significant decreased mortality. However, this study was not blinded and was small in size, thus limiting its validity.…”

Section: Subgroup Analysesmentioning

confidence: 99%

See 3 more Smart Citations

Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis

et al. 2022

View full text Add to dashboard Cite

IntroductionIntensive care unit (ICU) lengths of stay are modified by ongoing need for haemodynamic support in critically ill patients. This is most commonly provided by intravenous vasopressor therapy. Midodrine has been used as an oral agent for haemodynamic support in patients with orthostatic hypotension or cirrhosis. However, its efficacy in treating shock in the ICU, particularly for patients weaning from intravenous vasopressors, remains uncertain. The objective of this systematic review is to determine the efficacy of midodrine in vasopressor dependent shock.Methods and analysisWe will search Ovid MEDLINE, Ovid Embase, CINAHL and Cochrane Library for observational trials and randomised controlled trials evaluating midodrine in critically ill patients from inception to 21 April 2022. We will also review unpublished data and relevant conference abstracts. Outcomes will include ICU length of stay, duration of intravenous vasopressor support, ICU mortality, hospital mortality, hospital length of stay and rates of ICU readmission. Data will be analysed in aggregate, where appropriate. We will evaluate risk of bias using the modified Cochrane tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations methodology. We will perform trial sequential analysis for the outcome of ICU length of stay.Ethics and disseminationEthics approval is not required as primary data will not be collected. Findings of this review will be disseminated through peer-related publication and will inform future clinical trials.PROSPERO registration numberCRD42021260375.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

Section: Subgroup Analysesmentioning

confidence: 99%

Section: Subgroup Analysesmentioning

confidence: 99%

See 2 more Smart Citations

Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…5–7 Recent meta-analysis and retrospective observational studies, however, have revealed only a limited role of midodrine in the treatment of OH and paltry evidence to reduce intravenous vasopressor requirements. 8–10 These studies collectively therefore highlight a constrained role of midodrine as a direct pharmacological bolster for cardiogenic hypotension at least within the confines of fixed-dose regimens on which most of these conclusions are based. Nonetheless, there is widespread use and thus the potential for applications in difficult situations such as the HFrEF cases described in this series.…”

Section: Introductionmentioning

confidence: 97%

Midodrine to optimize heart failure therapy in patients with concurrent hypotension

Shiu

Grewal

Kozik

2022

SAGE Open Medical Case Reports

View full text Add to dashboard Cite

According to the Centers for Disease Control and Prevention statistics, about 6.2 million adults in the United States have heart failure. Guideline-Directed Medical Therapy (GDMT) involving the use of renin-angiotensin-aldosterone system inhibitors with or without a neprilysin inhibitor, β-blockers, mineralocorticoid-receptor-antagonists, and sodium-glucose cotransporter-2 inhibitors serve as the backbone for heart failure with reduced ejection fraction (HFrEF) therapy. However, in patients with refractory hypotension, the initiation of GDMT may not be possible. We present four cases where the use of midodrine, an alpha adrenergic agonist, serves as bridge therapy for the initiation or continuation of GDMT with marked clinical improvement. These cases illustrate how exacerbations of HFrEF may be ameliorated with outpatient midodrine titration among patients with baseline, persistent hypotension such that GDMT may be better tolerated.

show abstract

The Use of Midodrine as an Adjunctive Therapy to Liberate Patients from Intravenous Vasopressors: A Systematic Review and Meta-analysis of Randomized Controlled Studies

et al. 2023

View full text Add to dashboard Cite

Background Studies evaluating the role of midodrine as an adjunctive therapy to liberate patients with shock from intravenous (IV) vasopressors have yielded mixed results. The aim of our study was to evaluate the efficacy and safety of midodrine as an adjunctive therapy to liberate patients with shock from IV vasopressors. Methods Electronic searches of the MEDLINE, EMBASE, and Cochrane databases through April 2022 for randomized controlled trials (RCTs) that evaluated the use of midodrine versus control in patients with shock and a low dose of IV vasopressors. The primary outcome was total IV vasopressor time, while the secondary outcomes included time-to-IV vasopressor discontinuation, IV vasopressor restart, intensive care unit (ICU) length of stay (LOS), hospital LOS, and incidence of bradycardia. Results The final analysis included four RCTs with a total of 314 patients: 158 in the midodrine group and 156 in the control group, with a weighted mean age of 64 years (54.2% men). There was no significant difference in the total IV vasopressor time between the midodrine and control groups (standardized mean difference [SMD] − 0.53; 95% confidence interval [CI] − 1.38 to 0.32, p = 0.22; I 2 = 92%). Also, there were no significant differences between the two groups in the time-to-IV vasopressor discontinuation (SMD − 0.05; 95% CI − 0.57 to 0.47, p = 0.09), IV vasopressor restart (19.3 vs. 28.3%; risk ratio [RR] 0.74; 95% 0.25–2.20, p = 0.59), ICU LOS (SMD − 0.49; 95% CI − 1.30 to 0.33, p = 0.24), and hospital LOS (SMD 0.01; 95% CI − 0.27 to 0.29, p = 0.92). However, compared with the control group, the midodrine group had a higher risk of bradycardia (15.3 vs. 2.1% RR 5.56; 95% CI 1.54–20.05, p = 0.01). Conclusions Among patients with vasopressor-dependent shock, midodrine was not associated with early liberation of vasopressor support or shorter ICU or hospital length of stay. Adding midodrine increased the risk of bradycardia. Further large RCTs are needed to better evaluate the efficacy and safety of midodrine in liberating patients from IV vasopressors. Supplementary Information The online version contains supplementary material available at 10.1007/s40119-023-00301-0.

show abstract

A pilot, feasibility, randomised controlled trial of midodrine as adjunctive vasopressor for low-dose vasopressor-dependent hypotension in intensive care patients: The MAVERIC study

Cited by 17 publications

References 24 publications

Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis

Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis

Midodrine to optimize heart failure therapy in patients with concurrent hypotension

The Use of Midodrine as an Adjunctive Therapy to Liberate Patients from Intravenous Vasopressors: A Systematic Review and Meta-analysis of Randomized Controlled Studies

Contact Info

Product

Resources

About