Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial

J Hepatol. 2018 Dec;69(6):1250-1259. doi: 10.1016/j.jhep.2018.08.006. Epub 2018 Aug 21.


Background & aims: Patients with decompensated cirrhosis on the waiting list for liver transplantation (LT) commonly develop complications that may preclude them from reaching LT. Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis. The aim of this study was to investigate whether treatment with midodrine, an alpha-adrenergic vasoconstrictor, together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT.

Methods: A multicenter, randomized, double-blind, placebo-controlled trial (NCT00839358) was conducted, including 196 consecutive patients with cirrhosis and ascites awaiting LT. Patients were randomly assigned to receive midodrine (15-30 mg/day) and albumin (40 g/15 days) or matching placebos for one year, until LT or drop-off from inclusion on the waiting list. The primary endpoint was incidence of any complication (renal failure, hyponatremia, infections, hepatic encephalopathy or gastrointestinal bleeding). Secondary endpoints were mortality, activity of endogenous vasoconstrictor systems and plasma cytokine levels.

Results: There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up (p = 0.402) or one-year mortality (p = 0.527). Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin -4.3 vs. 0.1 ng/ml.h, p < 0.001; aldosterone -38 vs. 6 ng/dl, p = 0.02, at week 48 vs. baseline). Plasma norepinephrine only decreased slightly at week 4. Neither arterial pressure nor plasma cytokine levels changed significantly.

Conclusions: In patients with cirrhosis awaiting LT, treatment with midodrine and albumin, at the doses used in this study, slightly suppressed the activity of vasoconstrictor systems, but did not prevent complications of cirrhosis or improve survival.

Lay summary: Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant. Circulatory dysfunction is a key factor behind a number of complications. This study was aimed at investigating whether treating patients with midodrine (a vasoconstrictor) and albumin would improve circulatory dysfunction and prevent complications. This combined treatment, at least at the doses administered in this study, did not prevent the complications of cirrhosis or improve the survival of these patients.

Keywords: Albumin; Ascites; Cirrhosis; Liver transplantation; Midodrine.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albumins / administration & dosage
  • Albumins / therapeutic use*
  • Aldosterone / blood
  • Ascites
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hyponatremia / etiology
  • Hyponatremia / prevention & control
  • Kaplan-Meier Estimate
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / mortality
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Midodrine / administration & dosage
  • Midodrine / therapeutic use*
  • Norepinephrine / blood
  • Renal Insufficiency / etiology
  • Renal Insufficiency / prevention & control
  • Renin / blood
  • Shock / prevention & control*
  • Treatment Outcome
  • Vasoconstrictor Agents / administration & dosage
  • Vasoconstrictor Agents / therapeutic use*


  • Albumins
  • Vasoconstrictor Agents
  • Aldosterone
  • Midodrine
  • Renin
  • Norepinephrine

Associated data

  • ClinicalTrials.gov/NCT00839358