Hypoxic HepatitisPhase 2MARS in HHNCT01690845
Molecular Adsorbent Recirculating System (MARS®) in Hypoxic Hepatitis
A Phase 2 study testing MARS in people with Hypoxic Hepatitis and Ischemic Hepatitis, run by Medical University of Vienna at 2 sites in 2 countries.
Trial summary
Hypoxic hepatitis (HH) is reported to be the most frequent cause of elevated aminotransferase levels in hospital. Up to 10 % of critically ill patients develop HH during the course of their intensive care unit (ICU) stay. Occurrence of HH is a life threatening event and ICU-mortality is reported to be up to 60%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypoxic Hepatitis, Ischemic Hepatitis, Shock Liver
- What is being tested?
- MARS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jun 2012to Jun 2017
- Phase
- Phase 2
- 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
- presence of severe hypoxic hepatitis with aminotransferase levels > 40 times the upper limit of normal
- duration of hypoxic hepatitis more than 12 hours
- age >/= 18 years
Who cannot join
- age < 18 years
- pregnancy
- DNR - order
- liver cirrhosis
- Cardiopulmonary resuscitation with unknown neurological outcome and/or hypoxic brain damage
- Expected survival of less than 24 hours
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Austria1 site, 1 recruiting
- Recruiting
Medical University Vienna, Dpt. of Internal Medicine 3, Div. of Gastroenterology and Hepatology
Vienna, State of Vienna, 1090
Valentin Fuhrmann, Prof, 0043140400 ext. 4741, valentin.fuhrmann@meduniwien.ac.at
Thomas Horvatitis, MD, 0043140400 ext. 4741, thomas.horvatitis@meduniwien.ac.at
Germany1 site, 1 recruiting
- Recruiting
University Medical Center Hamburg-Eppendorf
Hamburg, Free and Hanseatic City of Hamburg, 20246
Stefan Kluge, Prof
About this study
Official title: Molecular Adsorbent Recirculating System (MARS®) for the Treatment of Patients With Hypoxic Hepatitis - a Prospective Randomized Controlled Clinical Study
Hypoxic hepatitis (HH) is reported to be the most frequent cause of elevated aminotransferase levels in hospital. Up to 10 % of critically ill patients develop HH during the course of their intensive care unit (ICU) stay. Occurrence of HH is a life threatening event and ICU-mortality is reported to be up to 60%. Early therapeutic intervention is of central prognostic importance in patients with HH to improve the hemodynamic impairment as early as possible, to reduce hyperammonemia and hepatic encephalopathy, to avoid progression of organ failure and to improve outcome. Studies reported that Molecular Adsorbent Recirculating System (MARS®) therapy improved the hemodynamic situation in patients with acute and acute on chronic liver failure. The study hypothesis is that MARS® therapy in critically ill patients with severe HH improves hepatic hemodynamics and function and consecutively the course of the disease. 40 patients with suffering of severe HH with aminotransferase levels > 40 times the upper limit of normal of more than 12 hours will be randomized 1:1 to MARS® therapy (n=20) or conventional therapy (n=20). 4 MARS®-sessions will be performed on three consecutive days, each for at least 12 hours. Treatment will be continued under special circumstances. The maximum duration of the treatment phase is 7 days. The primary endpoint is the difference of the indocyanine plasma disappearance rate at day 7. The expected duration of the study is 2 years.
- Conditions
- Hypoxic Hepatitis, Ischemic Hepatitis, Shock Liver, Hypoxic Liver Injury, Acute Liver Failure
- Being tested
- MARS
- Medical subject headings
- Liver Failure, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MARSDevice
Also called Molecular adsorbent recirculating system (MARS®)
Molecular adsorbent recirculating system (MARS®) can be used in patients with acute liver failure for bridging to liver transplantation. Studies reported that MARS® therapy improved the hemodynamic situation in patients with acute and acute on chronic liver failure. Several groups observed an increase in arterial pressure, systemic vascular resistance index, a decrease in portal pressure and improvement of renal blood flow. Furthermore, studies demonstrated that MARS therapy reduces ammonia levels and improves hepatic encephalopathy.
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | Patients with severe HH will be treated with standard medical therapy (i.e. vasopressor support with norepinephrine in refractory hypotension = RR mean < 65 mmHg, positive inotropic support with dobutamine if the central venous oxygen saturation < 70%, renal replacement therapy in case of severe metabolic acidosis and/or renal failure, antibiotic treatment in case of suspected or proven infection, mechanical ventilation in case of severe hypoxemia or hypercapnia and/or GCS <= 8. |
| MARS-Group | Experimental | 20 patients will be allocated by randomization to the MARS arm. Additionally to standard medical therapy they will receive 4 MARS sessions on three consecutive days, MARS® therapy will be applied for at least 12 hours per session. Thereafter, MARS® treatment will be continued if the patient still has increasing aminotransferase levels, requires vasopressor support or suffers from cholestasis (defined as serum bilirubin levels > 5 mg/dL) for 3 sessions again. There will be a maximum of 7 MARS ® sessions per patient. Receives: Device: MARS |
What is being measured
The primary outcome is the main question the study is designed to answer.
difference of the indocyanine plasma disappearance rate (ICG-PDR)
The primary endpoint will be the difference of the indocyanine plasma disappearance rate (ICG-PDR) at day 7. Only in case of major differences in baseline values of ICG-PDR we will use the change from baseline to day 7 of ICG-PDR (delta ICG-PDR) as outcome. Assuming normal distribution of ICG-PDR, we will formally test the null-hypothesis of no difference between intervention group and control using an independent sample t-test. The assumption of a normal distribution will be founded on visually inspecting a histogram and using the Shapiro Wilks test for normal distribution. If the assumption of normality does not hold data will be compared using the Mann-Whitney U-test. A p-level of < 0.05 will be considered statistically significant. Furthermore a linear random coefficient model will be used to incorporate daily measurements of ICG-PDR during the course of the study in terms of a repeated measures design.
Measured: Days 1-7
Secondary outcomes (16)
duration of vasopressor support
Measured: 1-28
ICU - length of stay
Measured: 1-28
hospital - length of stay
Measured: 1-90
7-day mortality
Measured: 7 days
28 day mortality
Measured: 28 days
number of organ failure on day 7
Measured: 7 days
number of organ failure on day 28
Measured: 28 days
markers of liver function
especially occurrence of jaundice (defined as total bilirubin levels > 3 mg/dL) will be documented
Measured: 1-28
number of vasopressor free days
Measured: 28 days
systemic hemodynamics
systemic blood pressure, heart rate, cardiac index, central venous oxygen saturation, systemic vascular resistance index, global enddiastolic volume index, stroke volume variation, extravascular lung water index, pulse pressure variation, intrathoracic blood volume index, cardiac function index, central venous pressure
Measured: 7 days
number of complications of HH
following complications will be encountered: cholestasis, secondary sclerosing cholangitis, hepatic encephalopathy grade 3 \& 4, hypoglycemia, intraabdominal hypertension, new onset of infections, renal failure, hepatopulmonary syndrome
Measured: 1-28
biomarkers
blood samples will be collected the assess markers of inflammation, markers of endothelial function, markers of cardiac function, markers of cholestasis, markers of liver cell necrosis etc
Measured: 0-28
duration of mechanical ventilation
Measured: 1-28
necessity of renal replacement therapy
Measured: 1-28
duration of renal replacement therapy
Measured: 1-28
90 days mortality
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2012 (estimated)
- Study startJun 2012
- Primary completionJun 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypoxic HepatitisStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Valentin Fuhrmann, Medical University of Vienna
- Investigators
- Valentin Fuhrmann, Prof, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01690845
- Sponsor's protocol ID
- 10712010
- Acronym
- MARS in HH
- Status last verified
- Sep 2016
- First submitted
- 16 Sep 2012
- Last updated
- 22 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Adsorbent Recirculating System (MARS®) for the Treatment of Patients With Hypoxic Hepatitis - a Prospective Randomized Controlled Clinical Study
- ClinicalTrials.gov ID
- NCT01690845
- Acronym / sponsor ID
- MARS in HH / 10712010
- Conditions
- Hypoxic Hepatitis, Ischemic Hepatitis, Shock Liver, Hypoxic Liver Injury, Acute Liver Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Jun 2017 (estimated)
- First posted
- 24 Sep 2012 (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.
Hypoxic hepatitis (HH) is reported to be the most frequent cause of elevated aminotransferase levels in hospital. Up to 10 % of critically ill patients develop HH during the course of their intensive care unit (ICU) stay. Occurrence of HH is a life threatening event and ICU-mortality is reported to be up to 60%. Early therapeutic intervention is of central prognostic importance in patients with HH to improve the hemodynamic impairment as early as possible, to reduce hyperammonemia and hepatic encephalopathy, to avoid progression of organ failure and to improve outcome. Studies reported that Molecular Adsorbent Recirculating System (MARS®) therapy improved the hemodynamic situation in patients with acute and acute on chronic liver failure. The study hypothesis is that MARS® therapy in critically ill patients with severe HH improves hepatic hemodynamics and function and consecutively the course of the disease. 40 patients with suffering of severe HH with aminotransferase levels > 40 times the upper limit of normal of more than 12 hours will be randomized 1:1 to MARS® therapy (n=20) or conventional therapy (n=20). 4 MARS®-sessions will be performed on three consecutive days, each for at least 12 hours. Treatment will be continued under special circumstances. The maximum duration of the treatment phase is 7 days. The primary endpoint is the difference of the indocyanine plasma disappearance rate at day 7. The expected duration of the study is 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –Patients with severe HH will be treated with standard medical therapy (i.e. vasopressor support with norepinephrine in refractory hypotension = RR mean < 65 mmHg, positive inotropic support with dobutamine if the central venous oxygen saturation < 70%, renal replacement therapy in case of severe metabolic acidosis and/or renal failure, antibiotic treatment in case of suspected or proven infection, mechanical ventilation in case of severe hypoxemia or hypercapnia and/or GCS <= 8. |
| MARS-Group | Experimental | Device: MARS20 patients will be allocated by randomization to the MARS arm. Additionally to standard medical therapy they will receive 4 MARS sessions on three consecutive days, MARS® therapy will be applied for at least 12 hours per session. Thereafter, MARS® treatment will be continued if the patient still has increasing aminotransferase levels, requires vasopressor support or suffers from cholestasis (defined as serum bilirubin levels > 5 mg/dL) for 3 sessions again. There will be a maximum of 7 MARS ® sessions per patient. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- presence of severe hypoxic hepatitis with aminotransferase levels > 40 times the upper limit of normal
- duration of hypoxic hepatitis more than 12 hours
- age >/= 18 years
Key exclusion criteria (6 listed)
- age < 18 years
- pregnancy
- DNR - order
- liver cirrhosis
- Cardiopulmonary resuscitation with unknown neurological outcome and/or hypoxic brain damage
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 |
|---|---|---|
| MARSAlso: Molecular adsorbent recirculating system (MARS®)Molecular adsorbent recirculating system (MARS®) can be used in patients with acute liver failure for bridging to liver transplantation. Studies reported that MARS® therapy improved the hemodynamic situation in patients with acute and acute on chronic liver failure. Several groups observed an increase in arterial pressure, systemic vascular resistance index, a decrease in portal pressure and improvement of renal blood flow. Furthermore, studies demonstrated that MARS therapy reduces ammonia levels and improves hepatic encephalopathy. | Device | MARS-Group |
Primary outcome
difference of the indocyanine plasma disappearance rate (ICG-PDR)
Time frame: Days 1-7
The primary endpoint will be the difference of the indocyanine plasma disappearance rate (ICG-PDR) at day 7. Only in case of major differences in baseline values of ICG-PDR we will use the change from baseline to day 7 of ICG-PDR (delta ICG-PDR) as outcome. Assuming normal distribution of ICG-PDR, we will formally test the null-hypothesis of no difference between intervention group and control using an independent sample t-test. The assumption of a normal distribution will be founded on visually inspecting a histogram and using the Shapiro Wilks test for normal distribution. If the assumption of normality does not hold data will be compared using the Mann-Whitney U-test. A p-level of < 0.05 will be considered statistically significant. Furthermore a linear random coefficient model will be used to incorporate daily measurements of ICG-PDR during the course of the study in terms of a repeated measures design.
16 secondary outcomes
duration of vasopressor support
Time frame: 1-28
ICU - length of stay
Time frame: 1-28
hospital - length of stay
Time frame: 1-90
7-day mortality
Time frame: 7 days
28 day mortality
Time frame: 28 days
number of organ failure on day 7
Time frame: 7 days
number of organ failure on day 28
Time frame: 28 days
markers of liver function
Time frame: 1-28
number of vasopressor free days
Time frame: 28 days
systemic hemodynamics
Time frame: 7 days
number of complications of HH
Time frame: 1-28
biomarkers
Time frame: 0-28
duration of mechanical ventilation
Time frame: 1-28
necessity of renal replacement therapy
Time frame: 1-28
duration of renal replacement therapy
Time frame: 1-28
90 days mortality
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2016.
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.
Valentin Fuhrmann, Prof principal investigator
Medical University of Vienna
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MARS in people with Hypoxic Hepatitis and Ischemic Hepatitis, run by Medical University of Vienna at 2 sites in 2 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 3 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 22 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Austria, Germany. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Valentin Fuhrmann, Prof (0043140400 ext. 4741, valentin.fuhrmann@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
difference of the indocyanine plasma disappearance rate (ICG-PDR) (time frame: Days 1-7). 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 22 Sep 2016.