The Effect of Prometheus (R) Liver Support Dialysis on Cerebral Metabolism in Acute Liver Failure

The Effect of Prometheus (R) Liver Support Dialysis on Intracranial Pressure, Cerebral Oxidative Metabolism and Hemodynamics in Patients With Acute Liver Failure

The main objective of this study is to investigate the effect of Prometheus liver support dialysis on intracranial pressure, cerebral metabolism and circulation in patients with acute liver failure.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy; Intracranial Hypertension; Acute Liver Failure
• Intervention / Treatment: Device: Prometheus (R) liver support dialysis; Device: CVVHDF (Continuously Veno-Venous Hemodiafiltration)

Detailed Description

Acute liver failure (ALF) is a highly mortal medical condition often complicated by multiorgan failure. Apart from severe coagulopathy ALF is characterized by onset of hepatic encephalopathy and in many cases intracranial hypertension (ICH) with the risk of cerebral incarceration. The pathogenesis behind ICH is incompletely understood and the therapeutic options are limited. Prometheus (R) liver support dialysis offers a system that apart from regular high-flux hemodialysis to a certain extent is able of removing albumin-bound substances from the patient - a feature that theoretically could benefit patients with ALF.

In this study we intend to investigate the effect of 6-8 hours of Prometheus (R) liver support dialysis on cerebral metabolism, ICH and cerebral bloodflow (CBF) in patients with ALF. The study is designed as a open, prospective and randomized study, where a control-group treated with 6-8 hours of continuously veno-venous hemodiafiltration (CVVHDF) and standard medical treatment (SMT) is compared to the intervention group treated with Prometheus (R) liver support dialysis and SMT. The study is designed as a cross-over study so that included patients will be treated in both groups in a randomized order.

The primary end-points are treatment effect on intracranial pressure, CBF and cerebral oxidative metabolism (lactate/pyruvate-ratio). We use a intracranial monitoring system from Integra/Camino (R) (United States) in combination with CMA microdialysis system and bedside analyzer (CMA-600) (Stockholm, Sweden).

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • The liverfailure unit, Department of hepatology, Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• acute liver failure
• and grade II-IV encephalopathy
• and persistent raised arterial ammonia-concentration above 150 micromol/L
• and informed consent from closest relative and general practitioner

Exclusion Criteria:

• withdrawal of informed consent
• severe untreated infection
• active bleeding within 48 hours
• suspicion of malignant liver disease
• severe heart insufficiency or middle artery pressure below 60 mmHg in spite of vasoactive therapy
• pregnant or lactating women
• disseminated intravascular coagulation
• clinical suspicion of cerebral damage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Treatment with 6-8 hours of Prometheus (R) liver support dialysis	Device: Prometheus (R) liver support dialysis; 6-8 hours of dialysis
Active Comparator: 2; Treatment with 6-8 hours of CVVHDF	Device: CVVHDF (Continuously Veno-Venous Hemodiafiltration); 6-8 hours of dialysis with the CVVHDF system PrismaFlex offered by Gambro (Sweden).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
treatment effect on cerebral oxidative metabolism (lactate/pyruvate-ratio)	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
treatment effect on intracranial pressure	24 hours

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Peter N Bjerring, MD, Department of hepatology, Rigshospitalet

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: April 3, 2008
• First Submitted That Met QC Criteria: April 4, 2008
• First Posted (Estimate): April 9, 2008

Study Record Updates

• Last Update Posted (Estimate): July 27, 2011
• Last Update Submitted That Met QC Criteria: July 26, 2011
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Liver Failure; Hepatic Insufficiency; Hepatic Encephalopathy; Brain Diseases; Intracranial Hypertension; Liver Failure, Acute
• Other Study ID Numbers: ALFPROM-001; H-KF-2007-0006