Molecular Adsorbent Recirculating System (MARS®) in Hypoxic Hepatitis

Acute Liver Failure Clinical Trial

— MARS in HH  

Official title:

Molecular Adsorbent Recirculating System (MARS®) for the Treatment of Patients With Hypoxic Hepatitis - a Prospective Randomized Controlled Clinical Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01690845
• Other study ID #: 10712010
• Status: Recruiting
• Phase: Phase 2
• First received: September 16, 2012
• Last updated: September 21, 2016
• Start date: June 2012

Study information

• Verified date: September 2016
• Source: Medical University of Vienna
• Contact: Valentin Fuhrmann, Prof
• Phone: 0043140400
• Email: valentin.fuhrmann[@]meduniwien.ac.at
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Liver Failure
• Anoxia
• Hepatitis
• Hepatitis A
• Hypoxic Hepatitis
• Hypoxic Liver Injury
• Ischemic Hepatitis
• Liver Failure
• Liver Failure, Acute
• Shock Liver

Intervention

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.

Locations

Country	Name	City	State
Austria	Medical University Vienna, Dpt. of Internal Medicine 3, Div. of Gastroenterology and Hepatology	Vienna
Germany	University Medical Center Hamburg-Eppendorf	Hamburg

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	difference of the indocyanine plasma disappearance rate (ICG-PDR)	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.	Days 1-7	No
Secondary	duration of vasopressor support		1-28	No
Secondary	ICU - length of stay		1-28	No
Secondary	hospital - length of stay		1-90	No
Secondary	7-day mortality		7 days	No
Secondary	28 day mortality		28 days	No
Secondary	number of organ failure on day 7		7 days	No
Secondary	number of organ failure on day 28		28 days	No
Secondary	markers of liver function	especially occurrence of jaundice (defined as total bilirubin levels > 3 mg/dL) will be documented	1-28	No
Secondary	number of vasopressor free days		28 days	No
Secondary	systemic hemodynamics	systemic blood pressure, heart rate, cardiac index, central venous oxygen saturation, systemic vascular resistance 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	7 days	No
Secondary	number of complications of HH	following complications will be encountered: cholestasis, secondary sclerosing cholangitis, hepatic encephalopathy grade 3 & 4, hypoglycemia, intraabdominal hypertension, new onset of infections, renal failure, hepatopulmonary syndrome	1-28	Yes
Secondary	biomarkers	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	0-28	No
Secondary	duration of mechanical ventilation		1-28	No
Secondary	necessity of renal replacement therapy		1-28	No
Secondary	duration of renal replacement therapy		1-28	No
Secondary	90 days mortality		90 days	No