Acute Liver FailureNCT00670124
Hypothermia to Prevent High Intracranial Pressure in Patients With Acute Liver Failure
A study testing Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero in people with Acute Liver Failure and Intracranial Hypertension, run by Copenhagen University Hospital, Rigshospitalet at 4 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Liver Failure, Intracranial Hypertension
- What is being tested?
- Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Jan 2005to Jun 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- no or withdrawn informed consent
- pregnant or breast feeding women
- uncontrollable infection
- hemodynamically instable patients
- active bleeding
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United Kingdom2 sites
Dept. of Intensive Care
Birmingham
Institute for Liver Studies, King's College Hospital
London
United States1 site
Division of Hepatology, Feinberg School of Medicine, Northwestern University
Chicago, Illinois, 60610
About this study
Official title: Pilot Trial on the Effect of Mild Hypothermia on Intracranial Pressure in Patients With Hyperacute Liver Failure
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.
Read the 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.
- Conditions
- Acute Liver Failure, Intracranial Hypertension
- Being tested
- Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero
- Medical subject headings
- Liver Failure, Acute, Intracranial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypothermia by the use of Blanketrol II, Cincinnati Sub-ZeroDevice
Also called Cooling device: Blanketrol II, Cincinnati Sub-Zero
The patients are placed on a cooling mattress and body-core temperature is regulated to 33° C.
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | Standard medical treatment |
| 2 | Active comparator | Standard medical treatment plus hypothermia (33°C) maintained for 72 hours Receives: Device: Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effect of hypothermia on preventing development of ICP higher than 25 mmHg
Measured: 72 hours
Secondary outcomes (2)
The effect of hypothermia on preserving normal cerebral oxidative metabolism evaluated by cerebral microdialysis
Measured: 72 hours
The effect of hypothermia on severity of infections
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2008 (estimated)
- Study startJan 2005
- Primary completionJan 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Liver FailureStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Birmingham, Northwestern University
- Responsible party
- Principal investigator, Dr. Fin Stolze Larsen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Fin S Larsen, MD, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00670124
- Sponsor's protocol ID
- ALFHypothermia01
- Status last verified
- Nov 2014
- First submitted
- 29 Apr 2008
- Last updated
- 5 Nov 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Trial on the Effect of Mild Hypothermia on Intracranial Pressure in Patients With Hyperacute Liver Failure
- ClinicalTrials.gov ID
- NCT00670124
- Acronym / sponsor ID
- ALFHypothermia01
- Conditions
- Acute Liver Failure, Intracranial Hypertension
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- University Hospital Birmingham, Northwestern University
- Study start
- Jan 2005
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 1 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | –Standard medical treatment |
| 2 | Active comparator | Device: Hypothermia by the use of Blanketrol II, Cincinnati Sub-ZeroStandard medical treatment plus hypothermia (33°C) maintained for 72 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- no or withdrawn informed consent
- pregnant or breast feeding women
- uncontrollable infection
- hemodynamically instable patients
- active bleeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hypothermia by the use of Blanketrol II, Cincinnati Sub-ZeroAlso: Cooling device: Blanketrol II, Cincinnati Sub-ZeroThe patients are placed on a cooling mattress and body-core temperature is regulated to 33° C. | Device | 2 |
Primary outcome
The effect of hypothermia on preventing development of ICP higher than 25 mmHg
Time frame: 72 hours
2 secondary outcomes
The effect of hypothermia on preserving normal cerebral oxidative metabolism evaluated by cerebral microdialysis
Time frame: 72 hours
The effect of hypothermia on severity of infections
Time frame: 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fin S Larsen, MD principal investigator
Copenhagen University Hospital, Rigshospitalet
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero in people with Acute Liver Failure and Intracranial Hypertension, run by Copenhagen University Hospital, Rigshospitalet at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom, United States, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The effect of hypothermia on preventing development of ICP higher than 25 mmHg (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2014.