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

Sponsor

Rigshospitalet, Denmark (Other)

Overall Status

Completed

CT.gov ID

NCT00655304

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Liver Failure Hepatic Encephalopathy Intracranial Hypertension	Device: Prometheus (R) liver support dialysis Device: CVVHDF (Continuously Veno-Venous Hemodiafiltration)	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Dec 1, 2010

Actual Study Completion Date :

Jun 1, 2011

Arms and Interventions

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).

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).

Outcome Measures

Primary Outcome Measures

treatment effect on cerebral oxidative metabolism (lactate/pyruvate-ratio) [24 hours]

Secondary Outcome Measures

treatment effect on intracranial pressure [24 hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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