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

• DOI: 10.1016/j.jhep.2018.08.006
• Publication Date: 2018-08-21T02:17:55Z
• Authors: Elsa Solà; Cristina Solé; Macarena Simón-Ta...; Marta Martín-Llahí; José Castellote; Rita Garcia-Martínez; Rebeca Moreira; Maria Torrens; Francisca Márquez; Núria Fabrellas; Gloria de Prada; Patrícia Huelin; Eva Lopez Benaiges; Meritxell Ventura; Marcela Manríquez; André Nazar; Xavier Ariza; Pilar Suñé; Isabel Graupera; Elisa Pose; Jordi Colmenero; Marco Pavesi; Mónica Guevara; Miquel Navasa; Xavier Xiol; Joan Córdoba; Victor Vargas; Pere Ginès
• Keywords: Adult; Liver Cirrhosis; Male; 0303 health sciences; Ascites; Shock; Kaplan-Meier Estimate; Middle Aged; Liver Transplantation; 3. Good health; Midodrine; Norepinephrine; 03 medical and health sciences; Double-Blind Method; Albumins; Renin; Humans; Female; Renal Insufficiency; Aldosterone; Aged; Follow-Up Studies; Hyponatremia

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.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.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.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.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.