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

NCT00839358 | Completed Phase 4 DMC

• 3 other identifiers: MACHT07/044307/90077
• Study Type: interventional
• Target: 199
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Failure; Hyponatremia; Sepsis; Hepatic Encephalopathy; Gastrointestinal Bleeding

Keywords

cirrhosis; renal failure; midodrine; albumine

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (2)

Albumin plus midodrine

ACTIVE COMPARATOR

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; Drug: Midodrine

salin solution plus pills

PLACEBO COMPARATOR

Placebo of albumin in the same schedule thats in arm 1; placebo of midodrine in the same schedule thats in arm 1.

Drug: albumin; Drug: Placebo

Interventions

albumin DRUG

albumine 40 g every 15 days

Also known as: Albumina Grifols

Albumin plus midodrine; salin solution plus pills

Midodrine DRUG

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.

Also known as: Gutron

Albumin plus midodrine

Placebo DRUG

saline solution

Also known as: Grifols saline solution

salin solution plus pills

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with cirrhosis in the waiting list for liver transplant
• Patients with ascites or diuretic treatment
• To have written inform consent

You may not qualify if:

• 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
• Respiratory or cardiac failure
• HIV positive

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead
• Maternal-Infantil Vall d´Hebron Hospital: collaborator
• Hospital Universitari de Bellvitge: collaborator

Study Sites (1)

Hospital Clinic

Villarroel 170, Barcelona, 08870, Spain

Location

Related Publications (6)

• 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.

  PMID: 19158001 BACKGROUND

• Martin-Llahi M, Pepin MN, Guevara M, Diaz F, Torre A, Monescillo A, Soriano G, Terra C, Fabrega E, Arroyo V, Rodes J, Gines 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.

  PMID: 18471512 BACKGROUND

• 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. doi: 10.1002/hep.20262.

  PMID: 15239086 BACKGROUND

• Salerno F, Gerbes A, Gines P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep;56(9):1310-8. doi: 10.1136/gut.2006.107789. Epub 2007 Mar 27. No abstract available.

  PMID: 17389705 BACKGROUND

• Guevara M, Gines P. Hepatorenal syndrome. Dig Dis. 2005;23(1):47-55. doi: 10.1159/000084725.

  PMID: 15920325 BACKGROUND

• Sola E, Sole C, Simon-Talero M, Martin-Llahi M, Castellote J, Garcia-Martinez R, Moreira R, Torrens M, Marquez F, Fabrellas N, de Prada G, Huelin P, Lopez Benaiges E, Ventura M, Manriquez M, Nazar A, Ariza X, Sune P, Graupera I, Pose E, Colmenero J, Pavesi M, Guevara M, Navasa M, Xiol X, Cordoba J, Vargas V, Gines P. Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial. J Hepatol. 2018 Dec;69(6):1250-1259. doi: 10.1016/j.jhep.2018.08.006. Epub 2018 Aug 21.

  PMID: 30138685 DERIVED

MeSH Terms

Conditions

Renal Insufficiency; Hyponatremia; Sepsis; Hepatic Encephalopathy; Gastrointestinal Hemorrhage; Fibrosis

Interventions

Albumins; Midodrine

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Gastrointestinal Diseases; Hemorrhage

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Pere Ginès

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Hepatology Unit

Study Record Dates

• First Submitted: February 6, 2009
• First Posted: February 9, 2009
• Study Start: August 1, 2008
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: August 18, 2016

Record last verified: 2016-08

Locations

ES (1)