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

Phase 4

Completed

• Conditions: Renal Failure; Hepatic Encephalopathy; Hyponatremia; Sepsis; Gastrointestinal Bleeding
• Interventions: Drug: albumin; Drug: Placebo; Drug: Midodrine

• Registration Number: NCT00839358
• Lead Sponsor: Hospital Clinic of Barcelona

Brief 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

Study Timeline

• Study Start: 2008-08
• Study First Submitted: 2009-02-06
• Study First Submitted QC: 2009-02-06
• Study First Posted: 2009-02-09
• Primary Completion: 2016-02
• Study Completion: 2016-02
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-17
• Last Update Posted: 2016-08-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 199

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
salin solution plus pills	Placebo	Placebo of albumin in the same schedule thats in arm 1; placebo of midodrine in the same schedule thats in arm 1.
Albumin plus midodrine	albumin	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.
salin solution plus pills	albumin	Placebo of albumin in the same schedule thats in arm 1; placebo of midodrine in the same schedule thats in arm 1.
Albumin plus midodrine	Midodrine	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.

Primary Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

Hospital Clinic; 🇪🇸 Villarroel 170, Barcelona, Spain