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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Hospital Clinic of Barcelona
Sponsor:
Collaborators:
Maternal-Infantil Vall d´Hebron Hospital
Hospital Universitari de Bellvitge
Information provided by (Responsible Party):
Pere Gines, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:
NCT00839358
First received: February 6, 2009
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Renal Failure
Hyponatremia
Sepsis
Hepatic Encephalopathy
Gastrointestinal Bleeding
Drug: albumin
Drug: Midodrine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Midodrine and Albumin for Cirrhotic Patients in the Waiting List for Liver Transplantation

Resource links provided by NLM:


Further study details as provided by Hospital Clinic of Barcelona:

Primary Outcome Measures:
  • To evaluate complications (renal failure, hepatic encephalopathy, hyponatremia, infection and gastrointestinal bleeding) in patients with cirrhosis awaiting for liver transplant. [ Time Frame: When 97 patients are included (% of the whole population) ] [ Designated as safety issue: No ]

Estimated Enrollment: 194
Study Start Date: August 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Albumin plus 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.
Drug: albumin
albumine 40 g every 15 days
Other Name: Albumina Grifols
Drug: 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.
Other Name: Gutron
Placebo Comparator: salin solution plus pills
Placebo of albumin in the same schedule thats in arm 1; placebo of midodrine in the same schedule thats in arm 1.
Drug: albumin
albumine 40 g every 15 days
Other Name: Albumina Grifols
Drug: Placebo
saline solution
Other Name: Grifols saline solution

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
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00839358

Contacts
Contact: Pere Gines, MD 0034932275753 pgines@clinic.ub.es
Contact: Monica Guevara, MD 0034932275753 mguevara@clinic.ub.es

Locations
Spain
Hospital Clinic Recruiting
Villarroel 170, Barcelona, Spain, 08870
Contact: Pere Gines    0034972275753    pgines@clinic.ub.es   
Sub-Investigator: Juan Cordoba         
Sub-Investigator: Xavier Xiol         
Sub-Investigator: Monica Guevara         
Sponsors and Collaborators
Hospital Clinic of Barcelona
Maternal-Infantil Vall d´Hebron Hospital
Hospital Universitari de Bellvitge
Investigators
Principal Investigator: Pere Ginès Hospital Clinic of Barcelona
  More Information

Publications:
Responsible Party: Pere Gines, Chief of Hepatology Unit, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier: NCT00839358     History of Changes
Other Study ID Numbers: MACHT, 07/0443, 07/90077
Study First Received: February 6, 2009
Last Updated: March 3, 2014
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Hospital Clinic of Barcelona:
cirrhosis
renal failure
midodrine
albumine

Additional relevant MeSH terms:
Gastrointestinal Hemorrhage
Hemorrhage
Hepatic Encephalopathy
Hyponatremia
Renal Insufficiency
Sepsis
Gastrointestinal Diseases
Digestive System Diseases
Pathologic Processes
Liver Failure
Hepatic Insufficiency
Liver Diseases
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolic Diseases
Water-Electrolyte Imbalance
Kidney Diseases
Urologic Diseases
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Midodrine
Pharmaceutical Solutions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014