Effect of Midodrine and Albumine in the Prevention of Complications in Cirrhotic Patients Awaiting Liver Transplantation

Study Overview
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Brief Summary
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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
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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

Official Title
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Midodrine and Albumin for Cirrhotic Patients in the Waiting List for Liver Transplantation

Conditions
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Renal Failure, Hyponatremia, Sepsis, Hepatic Encephalopathy, Gastrointestinal Bleeding

Intervention / Treatment
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* Drug: albumin
* Drug: Midodrine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with cirrhosis in the waiting list for liver transplant Patients with ascites or diuretic treatment To have written inform consent Exclusion Criteria: Systolic blood pressure ≥150 mmHg and or diastolic blood pressure≥90 mmHg To have been treated with transjugular intrahepatic portosystemic shunt (TIPS) or surgical shunts Antibiotic treatment in the previous week before the inclusion in the study Respiratory or cardiac failure HIV positive

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Albumin plus midodrine<br>Albumin 40 g every 15 days during 1 year or until liver transplantation. Midodrine 5mg/8h. It can be increased according the value of mean arterial pressure. If there is no increase (defined as at least 10mmHGin MAP)midodrine can be increased at a dose of 10mg/8h. This treatment will be given during 1 year or until liver transplantation. | Drug: albumin<br>* albumine 40 g every 15 days<br>* Other names: Albumina Grifols;Drug: Midodrine<br>* 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.<br>* Other names: Gutron;|
| Placebo Comparator: salin solution plus pills<br>Placebo of albumin in the same schedule thats in arm 1; placebo of midodrine in the same schedule thats in arm 1. | Drug: albumin<br>* albumine 40 g every 15 days<br>* Other names: Albumina Grifols;Drug: Placebo<br>* saline solution<br>* Other names: Grifols saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate complications (renal failure, hepatic encephalopathy, hyponatremia, infection and gastrointestinal bleeding) in patients with cirrhosis awaiting for liver transplant. |  | When 97 patients are included (% of the whole population) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cirrhosis, renal failure, midodrine, albumine