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Hypothermia to Prevent High Intracranial Pressure in Patients With Acute Liver Failure

Primary Purpose

Acute Liver Failure, Intracranial Hypertension

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero
Sponsored by
Rigshospitalet, Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Liver Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • acute liver failure
  • and hepatic encephalopathy stage 3 or 4
  • and informed and written consent by closest relative(s)
  • and arterial ammonia concentration above 150 micromol/L or clinical suspicion of cerebral edema
  • and an ICP-measuring device

Exclusion Criteria:

  • no or withdrawn informed consent
  • pregnant or breast feeding women
  • uncontrollable infection
  • hemodynamically instable patients
  • active bleeding

Sites / Locations

  • Division of Hepatology, Feinberg School of Medicine, Northwestern University
  • Department of hepatology, Rigshospitalet
  • Dept. of Intensive Care
  • Institute for Liver Studies, King's College Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

1

2

Arm Description

Standard medical treatment

Standard medical treatment plus hypothermia (33°C) maintained for 72 hours

Outcomes

Primary Outcome Measures

The effect of hypothermia on preventing development of ICP higher than 25 mmHg

Secondary Outcome Measures

The effect of hypothermia on preserving normal cerebral oxidative metabolism evaluated by cerebral microdialysis
The effect of hypothermia on severity of infections

Full Information

First Posted
April 29, 2008
Last Updated
November 4, 2014
Sponsor
Rigshospitalet, Denmark
Collaborators
University Hospital Birmingham, Northwestern University Feinberg School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00670124
Brief Title
Hypothermia to Prevent High Intracranial Pressure in Patients With Acute Liver Failure
Official Title
Pilot Trial on the Effect of Mild Hypothermia on Intracranial Pressure in Patients With Hyperacute Liver Failure
Study Type
Interventional

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rigshospitalet, Denmark
Collaborators
University Hospital Birmingham, Northwestern University Feinberg School of Medicine

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Treatment options in patients with high intracranial pressure due to acute liver failure are limited. This study intends to evaluate the effect of prophylactic hypothermia on preventing high intracranial pressure and compromised cerebral oxidative metabolism.
Detailed Description
Acute liver failure (ALF) is associated with a high mortality. With severe hepatic encephalopathy and elevated arterial ammonia concentration (< 200 micromol/L) more than 50% of the patients will develop high intracranial pressure (ICP) and risk cerebral incarceration and death. The therapeutic options are limited in treating and preventing this condition and new interventions are much sought after. As in hypothermia used for patients after cardiac resuscitation it could be speculated that hypothermia and the reduced cerebral metabolic rate would contribute to neuroprotection and reduce the risk of cerebral hypertension in patients with ALF. We have designed this open, randomized and unblinded study in order to evaluate the effect of prophylactic hypothermia on ICP, cerebral hemodynamics and oxidative metabolism. Patients are randomized to standard medical treatment (SMT) or SMT and hypothermia 33° C for 72 hours using a cooling mattress (Blanketrol II, Cincinnati Sub-Zero). All patients will receive mechanical ventilation, antibiotics, inotropic support and monitored with invasive and non-invasive equipment in accordance to local guidelines. In Copenhagen monitoring cerebral hemodynamics includes: Placement of a intracranial pressure measuring catheter (Camino (R), Integra) for monitoring ICP. Furthermore, a microdialysis catheter (CMA-70) placed in brain cortex is used for monitoring brain metabolism. Finally, cerebral perfusion can be monitored by measuring mean flow velocity using transcranial doppler and/or oxygen saturation in blood from the jugular vein. Ethical considerations: The Helsinki II declaration will be followed and informed consent is mandatory for enrollment. In any patient where hypothermia is believed or suspected to be harmful the study should be stopped and the primary investigator should be notified immediately. All adverse effects will be recorded and published together with the full paper.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Liver Failure, Intracranial Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
No Intervention
Arm Description
Standard medical treatment
Arm Title
2
Arm Type
Active Comparator
Arm Description
Standard medical treatment plus hypothermia (33°C) maintained for 72 hours
Intervention Type
Device
Intervention Name(s)
Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero
Other Intervention Name(s)
Cooling device: Blanketrol II, Cincinnati Sub-Zero
Intervention Description
The patients are placed on a cooling mattress and body-core temperature is regulated to 33° C.
Primary Outcome Measure Information:
Title
The effect of hypothermia on preventing development of ICP higher than 25 mmHg
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
The effect of hypothermia on preserving normal cerebral oxidative metabolism evaluated by cerebral microdialysis
Time Frame
72 hours
Title
The effect of hypothermia on severity of infections
Time Frame
1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: acute liver failure and hepatic encephalopathy stage 3 or 4 and informed and written consent by closest relative(s) and arterial ammonia concentration above 150 micromol/L or clinical suspicion of cerebral edema and an ICP-measuring device Exclusion Criteria: no or withdrawn informed consent pregnant or breast feeding women uncontrollable infection hemodynamically instable patients active bleeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fin S Larsen, MD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Division of Hepatology, Feinberg School of Medicine, Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60610
Country
United States
Facility Name
Department of hepatology, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Dept. of Intensive Care
City
Birmingham
Country
United Kingdom
Facility Name
Institute for Liver Studies, King's College Hospital
City
London
Country
United Kingdom

12. IPD Sharing Statement

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Hypothermia to Prevent High Intracranial Pressure in Patients With Acute Liver Failure

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