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

This study has been completed.
Sponsor:
Collaborators:
University Hospital Birmingham
King's College London
Feinberg School of Medicine, Northwestern University
Information provided by:
Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT00670124
First received: April 29, 2008
Last updated: July 20, 2011
Last verified: July 2010
  Purpose

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.


Condition Intervention
Acute Liver Failure
Intracranial Hypertension
Device: Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Trial on the Effect of Mild Hypothermia on Intracranial Pressure in Patients With Hyperacute Liver Failure

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • The effect of hypothermia on preventing development of ICP higher than 25 mmHg [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The effect of hypothermia on preserving normal cerebral oxidative metabolism evaluated by cerebral microdialysis [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • The effect of hypothermia on severity of infections [ Time Frame: 1 week ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: January 2005
Study Completion Date: June 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 1
Standard medical treatment
Active Comparator: 2
Standard medical treatment plus hypothermia (33°C) maintained for 72 hours
Device: Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero
The patients are placed on a cooling mattress and body-core temperature is regulated to 33° C.
Other Name: Cooling device: Blanketrol II, Cincinnati Sub-Zero

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 SvjO2.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00670124

Locations
United States, Illinois
Division of Hepatology, Feinberg School of Medicine, Northwestern University
Chicago, Illinois, United States, 60610
Denmark
Department of hepatology, Rigshospitalet
Copenhagen, Denmark, 2100
United Kingdom
Dept. of Intensive Care
Birmingham, United Kingdom
Institute for Liver Studies, King`s College Hospital
London, United Kingdom
Sponsors and Collaborators
Rigshospitalet, Denmark
University Hospital Birmingham
King's College London
Feinberg School of Medicine, Northwestern University
Investigators
Principal Investigator: Fin S Larsen, MD Rigshospitalet, Denmark
  More Information

No publications provided

Responsible Party: Fin Stolze Larsen, MD, PhD, DSC, Department of Hepatology, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT00670124     History of Changes
Other Study ID Numbers: ALFHypothermia01
Study First Received: April 29, 2008
Last Updated: July 20, 2011
Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics

Additional relevant MeSH terms:
Hypertension
Hypothermia
Intracranial Hypertension
Liver Failure
Liver Failure, Acute
Body Temperature Changes
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Digestive System Diseases
Hepatic Insufficiency
Liver Diseases
Nervous System Diseases
Signs and Symptoms
Vascular Diseases

ClinicalTrials.gov processed this record on October 29, 2014