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

Sepsis Clinical Trial

— MACHT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00839358
• Other study ID #: MACHT
• Secondary ID: 07/044307/90077
• Status: Completed
• Phase: Phase 4
• First received: February 6, 2009
• Last updated: August 17, 2016
• Start date: August 2008
• Est. completion date: February 2016

Study information

• Verified date: August 2016
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 199
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Brain Diseases
• Gastrointestinal Bleeding
• Gastrointestinal Hemorrhage
• Hepatic Encephalopathy
• Hyponatremia
• Renal Failure
• Renal Insufficiency
• Sepsis

Intervention

Drug:
• albumin
albumine 40 g every 15 days
• Midodrine
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.
• Placebo
saline solution

Locations

Country	Name	City	State
Spain	Hospital Clinic	Villarroel 170	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona	Hospital Universitari de Bellvitge, Maternal-Infantil Vall d´Hebron Hospital

Country where clinical trial is conducted

Spain, 

References & Publications (5)

Alessandria C, Debernardi-Venon W, Carello M, Ceretto S, Rizzetto M, Marzano A. Midodrine in the prevention of hepatorenal syndrome type 2 recurrence: a case-control study. Dig Liver Dis. 2009 Apr;41(4):298-302. doi: 10.1016/j.dld.2008.09.014. Epub 2009 Jan 20. — View Citation

Guevara M, Ginès P. Hepatorenal syndrome. Dig Dis. 2005;23(1):47-55. Review. — View Citation

Martín-Llahí M, Pépin MN, Guevara M, Díaz F, Torre A, Monescillo A, Soriano G, Terra C, Fábrega E, Arroyo V, Rodés J, Ginès P; TAHRS Investigators. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008 May;134(5):1352-9. doi: 10.1053/j.gastro.2008.02.024. Epub 2008 Feb 14. — View Citation

Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep;56(9):1310-8. Epub 2007 Mar 27. Review. — View Citation

Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2004 Jul;40(1):55-64. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No