Midodrine versus placebo in patients with acute-on-chronic liver failure with ascites—A randomized trial (MIDAS trial)

BACKGROUND: Ascites is common in patients with acute-on-chronic liver failure (ACLF) and can complicate the course of ACLF due to circulatory dysfunction and hemodynamic compromise. Oral midodrine has been variably reported to improve hemodynamics and reduce complications of ascites in patients with decompensated cirrhosis, but its role in patients with high MELD ACLF remains unknown, which we aimed to assess. METHODS: In this single-center, double-blind, randomized trial, patients with ACLF were assigned 1:1 to receive midodrine (5-7.5 mg tid) or a placebo for 30 days, alongside standard care. Transplant-free survival (TFS) at 1 month was the primary outcome, while secondary outcomes included TFS at 3 months, the proportion of patients achieving ascites control, changes in mean arterial pressure (MAP) and plasma renin activity at 1 month, the incidence of cirrhosis complications, and diuretic-related complications. RESULTS: One hundred thirty patients with ACLF were enrolled. Midodrine use was not associated with improvement in TFS at 1 (HR, 0.99 [95% CI: 0.37-2.65]) and 3 months (HR, 0.93 [95% CI: 0.48-1.8]). Ascites control at day 30 (placebo: 9.2% [95% CI: 3.5-19] vs. midodrine: 20% [95% CI: 12.3-33.5]; p=0.08) and 90 (placebo: 44.6% [95% CI: 32.2-57.5] vs. midodrine: 53.8% [95% CI: 41-66.3]; p=0.29) was comparable. Midodrine increased the MAP (1.9 vs. 6.9 mm Hg; p=0.003) with an insignificant reduction in plasma renin activity levels (delta change: 0.22±1.6 vs. -1.6±2.2; p=0.09). Cirrhosis-related and diuretic-related complications were similar in both groups. CONCLUSIONS: Midodrine increases MAP in patients with ACLF and high MELD scores without TFS benefit and does not reduce the rate of ascites-related complications.