Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial

Abstract

Purpose: ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α₁-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement.

Methods: In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates.

Results: Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02).

Conclusion: Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.

Keywords: ICU discharge; Midodrine; Oral vasopressor; Persistent hypotension.

Fig. 1. Participant flow

ICU indicates intensive care unit, HDU indicates high dependency unit. ^aNumbers of participants not meeting inclusion or exclusion criteria are nonexclusive.

Fig. 2. Post hoc time-to-event analysis for time to vasopressor discontinuation

Kaplan-Meier curves for time to vasopressor discontinuation showed no difference in time to vasopressor discontinuation between the midodrine (navy blue solid line) and placebo (light blue dashed line) groups.