Molecular Adsorbent Recirculating System (MARS®) in Hypoxic Hepatitis (MARS in HH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Medical University of Vienna
Sponsor:
Information provided by (Responsible Party):
Valentin Fuhrmann, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01690845
First received: September 16, 2012
Last updated: September 19, 2012
Last verified: September 2012
  Purpose

Hypoxic hepatitis (HH) is reported to be the most frequent cause of elevated aminotransferase levels in hospital. Up to 10 % of critically ill patients develop HH during the course of their intensive care unit (ICU) stay. Occurrence of HH is a life threatening event and ICU-mortality is reported to be up to 60%. Early therapeutic intervention is of central prognostic importance in patients with HH to improve the hemodynamic impairment as early as possible, to reduce hyperammonemia and hepatic encephalopathy, to avoid progression of organ failure and to improve outcome. Studies reported that Molecular Adsorbent Recirculating System (MARS®) therapy improved the hemodynamic situation in patients with acute and acute on chronic liver failure. The study hypothesis is that MARS® therapy in critically ill patients with severe HH improves hepatic hemodynamics and function and consecutively the course of the disease. 40 patients with suffering of severe HH with aminotransferase levels > 40 times the upper limit of normal of more than 12 hours will be randomized 1:1 to MARS® therapy (n=20) or conventional therapy (n=20). 4 MARS®-sessions will be performed on three consecutive days, each for at least 12 hours. Treatment will be continued under special circumstances. The maximum duration of the treatment phase is 7 days. The primary endpoint is the difference of the indocyanine plasma disappearance rate at day 7. The expected duration of the study is 2 years.


Condition Intervention Phase
Hypoxic Hepatitis
Ischemic Hepatitis
Shock Liver
Hypoxic Liver Injury
Acute Liver Failure
Device: MARS
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Molecular Adsorbent Recirculating System (MARS®) for the Treatment of Patients With Hypoxic Hepatitis - a Prospective Randomized Controlled Clinical Study

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • difference of the indocyanine plasma disappearance rate (ICG-PDR) [ Time Frame: Days 1-7 ] [ Designated as safety issue: No ]
    The primary endpoint will be the difference of the indocyanine plasma disappearance rate (ICG-PDR) at day 7. Only in case of major differences in baseline values of ICG-PDR we will use the change from baseline to day 7 of ICG-PDR (delta ICG-PDR) as outcome. Assuming normal distribution of ICG-PDR, we will formally test the null-hypothesis of no difference between intervention group and control using an independent sample t-test. The assumption of a normal distribution will be founded on visually inspecting a histogram and using the Shapiro Wilks test for normal distribution. If the assumption of normality does not hold data will be compared using the Mann-Whitney U-test. A p-level of < 0.05 will be considered statistically significant. Furthermore a linear random coefficient model will be used to incorporate daily measurements of ICG-PDR during the course of the study in terms of a repeated measures design.


Secondary Outcome Measures:
  • duration of vasopressor support [ Time Frame: 1-28 ] [ Designated as safety issue: No ]
  • ICU - length of stay [ Time Frame: 1-28 ] [ Designated as safety issue: No ]
  • hospital - length of stay [ Time Frame: 1-90 ] [ Designated as safety issue: No ]
  • 7-day mortality [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • 28 day mortality [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • number of organ failure on day 7 [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • number of organ failure on day 28 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • markers of liver function [ Time Frame: 1-28 ] [ Designated as safety issue: No ]
    especially occurrence of jaundice (defined as total bilirubin levels > 3 mg/dL) will be documented

  • number of vasopressor free days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • systemic hemodynamics [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    systemic blood pressure, heart rate, cardiac index, central venous oxygen saturation, systemic vascular resistence index, global enddiastolic volume index, stroke volume variation, extravascular lung water index, pulse pressure variation, intrathoracic blood volume index, cardiac function index, central venous pressure

  • number of complications of HH [ Time Frame: 1-28 ] [ Designated as safety issue: Yes ]
    following complications will be encoutered: cholestasis, secondary sclerosing cholangitis, hepatic encephalopathy grade 3 & 4, hypoglycemia, intraabdominal hypertension, new onset of infections, renal failure, hepatopulmonary syndrome

  • biomarkers [ Time Frame: 0-28 ] [ Designated as safety issue: No ]
    blood samples will be collected the assess markers of inflammation, markers of endothelial function, markers of cardiac function, markers of cholestasis, markers of liver cell necrosis etc

  • duration of mechanical ventilation [ Time Frame: 1-28 ] [ Designated as safety issue: No ]
  • necessity of renal replacement therapy [ Time Frame: 1-28 ] [ Designated as safety issue: No ]
  • duration of renal replacement therapy [ Time Frame: 1-28 ] [ Designated as safety issue: No ]
  • 90 days mortality [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: June 2012
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Controll
Patients with severe HH will be treated with standard medical therapy (i.e. vasopressor support with norepinephrine in refractory hypotension = RR mean < 65 mmHg, positive inotropic support with dobutamine if the central venous oxygen saturation < 70%, renal replacement therapy in case of severe metabolic acidosis and/or renal failure, antibiotic treatment in case of suspected or proven infection, mechanical ventilation in case of severe hypoxemia or hypercapnia and/or GCS <= 8.
Experimental: MARS-Group
20 patients will be allocated by randomization to the MARS arm. Additionally to standard medical therapy they will receive 4 MARS sessions on three consecutive days, MARS® therapy will be applied for at least 12 hours per session. Thereafter, MARS® treatment will be continued if the patient still has increasing aminotransferase levels, requires vasopressor support or suffers from cholestasis (defined as serum bilirubin levels > 5 mg/dL) for 3 sessions again. There will be a maximum of 7 MARS ® sessions per patient.
Device: MARS
Molecular adsorbent recirculating system (MARS®) can be used in patients with acute liver failure for bridging to liver transplantation. Studies reported that MARS® therapy improved the hemodynamic situation in patients with acute and acute on chronic liver failure. Several groups observed an increase in arterial pressure, systemic vascular resistance index, a decrease in portal pressure and improvement of renal blood flow. Furthermore, studies demonstrated that MARS therapy reduces ammonia levels and improves hepatic encephalopathy.
Other Name: Molecular adsorbent recirculating system (MARS®)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • presence of severe hypoxic hepatitis with aminotransferase levels > 40 times the upper limit of normal
  • duration of hypoxic hepatitis more than 12 hours
  • age >/= 18 years

Exclusion Criteria:

  • age < 18 years
  • pregnancy
  • DNR - order
  • liver cirrhosis
  • Cardiopulmonary resuscitation with unknown neurological outcome and/or hypoxic brain damage
  • Expected survival of less than 24 hours
  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: NCT01690845

Contacts
Contact: Valentin Fuhrmann, Prof 0043140400 ext 4741 valentin.fuhrmann@meduniwien.ac.at
Contact: Thomas Horvatits, MD 0043140400 ext 4741 thomas.horvatits@meduniwien.ac.at

Locations
Austria
Medical University Vienna, Dpt. of Internal Medicine 3, Div. of Gastroenterology and Hepatology Recruiting
Vienna, Austria, 1090
Contact: Valentin Fuhrmann, Prof    0043140400 ext 4741    valentin.fuhrmann@meduniwien.ac.at   
Contact: Thomas Horvatitis, MD    0043140400 ext 4741    thomas.horvatitis@meduniwien.ac.at   
Principal Investigator: Valentin Fuhrmann, Prof         
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Valentin Fuhrmann, Prof Medical University Vienna
  More Information

No publications provided

Responsible Party: Valentin Fuhrmann, Associate Professor, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01690845     History of Changes
Other Study ID Numbers: 10712010
Study First Received: September 16, 2012
Last Updated: September 19, 2012
Health Authority: Austria: Ethikkommission

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Viral, Human
Liver Failure
Liver Failure, Acute
Wounds and Injuries
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepatic Insufficiency

ClinicalTrials.gov processed this record on August 19, 2014