Effect of Midodrine and Albumine in the Prevention of Complications in Cirrhotic Patients Awaiting Liver Transplantation
Condition: Renal Failure; Hyponatremia; Sepsis; Hepatic Encephalopathy; Gastrointestinal Bleeding
MeSH terms: Hepatic Encephalopathy; Gastrointestinal Hemorrhage; Brain Diseases; Renal Insufficiency; Hyponatremia
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of this study is to evaluate the effect of prolonged administration of albumin and
      midodrine on the prevention of complications (renal failure, sepsis, hemorrhage, hepatic
      encephalopathy and hyponatremia) in patients with cirrhosis in the waiting list for liver
      transplantation. One hundred and ninety four patients with cirrhosis and awaiting a liver
      transplantation will include in the study. Patients will be randomized to receive albumin and
      midodrine (treatment group) or administration of placebo (saline for albumine) and tablets
      with excipients without midodrine (control group). Patients will be followed-up during 12th
      months. In the treatment group albumin will be given at a dose of 40g every 15 days and
      midodrine 5mg tid, in addition with lactitol (conventional doses) and the specific treatment
      that patients require by cirrhosis. The group control will receive placebo in the same way
      than the treatment group in addition with lactitol and the specific treatment that they
      require by their disease. In all the patients liver and renal function test, hormones
      determination (renin, aldosterone, noradrenaline), and cytokines will be determined in basal
      conditions. All these determinations will be repeated at month 1st,3rd, 6th and 12th months.
      Before the inclusion in the study neuropsychological test and critical flicker test will be
      performed to diagnose minimum EH. These tests will be repeated at 3rd, 6th and 12th months.
      All the determinations will be repeated at any time that the patients develop any
      complication considered as an end point. In baseline conditions and at 3rd and 6th months a
      questionnaire of quality of life (SF36) will be performed. During a year of follow-up the
      number of paracentesis that patients require, the incidence of renal failure and EH and their
      relationship with hormonal activity and cytokine levels, free transplant survival and quality
      of life will be recorded.
    

Detailed description: 
      End point: To evaluate the effect of long term administration of albumin and midodrine on the
      prevention of complications associated with cirrhosis in patients with cirrhosis awaiting for
      liver transplantation.

      Secondary end points:

        -  To evaluate improvement in the ascites control

        -  To evaluate survival at 6 and 12 months.

        -  To evaluate the relationship between the development of complications and the activity
           of vasoconstrictor systems( renin, aldosterone and norepinephrine) as well as the levels
           of cytokines (TNF, IL6 and IL10)

        -  To evaluate quality of life

        -  To evaluate the presence and outcome of MHE
    

Intervention name(s): albumin; Midodrine; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): albumine 40 g every 15 days; Midodrine 5mg/8 hs, can be increase up to 8mg/8hs if there is a lack of increase in at least 10mmHg in mean arterial pressure after 15 days of treatment.; saline solution
Other intervention name(s): Albumina Grifols; Gutron; Grifols saline solution
Intervention MeSH terms: Midodrine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: cirrhosis; renal failure; midodrine; albumine