Acute-On-Chronic Liver FailureCYTOHEPNCT05019352
Cytokine Adsorption in Acute-on-chronic Liver Failure
A study testing CytoSorb cytokine adsorber and CRRT in people with Acute-On-Chronic Liver Failure and Renal Failure, run by Dr. Alexander Supady at 1 site in Germany.
Trial summary
The CYTOHEP study is a prospective, randomized, single center, open-label, controlled intervention trial to assess the benefit of extracorporeal hemoadsorption using the CytoSorb device in patients with acute-on-chronic liver failure. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Acute-On-Chronic Liver Failure, Renal Failure
- What is being tested?
- CytoSorb cytokine adsorber and CRRT
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteGermany
- Study dates
- 25 Oct 2021to 30 Jan 2023
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult patients (≥ 18 years) admitted to the University Medical Center Freiburg, Germany
- acute-on-chronic liver failure (ACLF) WITH acute kidney injury according to Kidney Disease: Improving Global Outcome (KDIGO) criteria stage 3 (≥ 3-fold increase of serum creatinine OR increase of serum creatinine to ≥ 4 mg/dl OR urine output ≤ 0.3 ml/kg/h for ≥ 24 hours OR anuria for ≥ 12 hours) AND serum bilirubin ≥ 5 mg/dl
Who cannot join
- known patient will against participation in the study or against the measures applied in the study
- a decision made prior to inclusion to stop further treatment of the patient within the next 24 hours
- no complete remission of malignancy including hepatocellular carcinoma within the past 12 months
- patients on the waiting list for liver transplant or the potential option for being listed for liver transplant within the next 6 months
- liver cirrhosis in patients after liver transplantation
- ongoing intermittent or continuous renal replacement therapy before study inclusion
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Clinic Freiburg
Freiburg im Breisgau, 79108
Alexander Supady, Dr., MPH
About this study
Official title: Cytokine Adsorption in Patients With Acute-on-chronic Liver Failure (CYTOHEP) - a Single Center, Open-label, Randomized, Controlled Intervention Trial
The CYTOHEP study is a prospective, randomized, single center, open-label, controlled intervention trial to assess the benefit of extracorporeal hemoadsorption using the CytoSorb device in patients with acute-on-chronic liver failure. The primary goal for this trial is to assess whether the CytoSorb device used in addition to continuous renal replacement therapy (CRRT) will be able to significantly reduce bilirubin in the patient blood as compared to the control group treated with CRRT alone (i.e., without extracorporeal hemoadsorption).
The rationale for this study is based on considerations about the role of systemic inflammation in acute decompensation of liver cirrhosis and ACLF, in-vitro data of the effectiveness CytoSorb for the removal of molecules with a pathophysiological role in acute-on-chronic liver failure, and recent reports on the successful use of extracorporeal hemoadsorption in combination with CRRT in critically ill patients with acute liver dysfunction.
Read the detailed description
Liver cirrhosis is a major healthcare problem. The clinical course of cirrhosis can be separated in compensated and decompensated cirrhosis. Patients with compensated cirrhosis are largely asymptomatic and the development of decompensating events is a major hallmark in the course of the disease as median survival decreases from 12 years to less than 2 years. The development of extrahepatic organ complications in decompensated cirrhosis has been identified as a major prognostic milestone and has been described as acute-on-chronic liver failure (ACLF). ACLF is understood as a dynamic process and may evolve within days leading to multi-organ failure with renal failure being the most common organ involvement (56%), followed by liver and coagulation failure (44% and 28%, respectively). ACLF is associated with a high 28-day mortality.
During recent years, systemic inflammation has been recognized as a major driver of hepatic decompensation and progression of liver cirrhosis to ACLF. Importantly, systemic inflammation was described as an important trigger for development of extrahepatic organ failures, such as renal failure, development of hepatopulmonary syndrome, cirrhotic cardiomyopathy and hepatic encephalopathy. Systemic inflammation is particularly relevant in the pathogenesis of acute hepatic decompensation and is also associated with reduced survival. Therefore, elimination of drivers of inflammatory response and inflammatory cytokines in addition to established therapeutic approaches aiming at a reduction of bacterial translocation and mitigation of portal hypertension may help control excessive inflammatory activity and thus support hepatic recompensation. Previous in-vitro examinations and studies in non-cirrhotic inflammatory disorders have shown that proinflammatory cytokines and other factors can effectively be removed by extracorporeal hemoadsorption in the CytoSorb adsorber.
The CYTOHEP study is designed as a prospective, randomized, single center, open-label, controlled intervention trial to assess the benefit of extracorporeal hemoadsorption using the CytoSorb device in patients with acute-on-chronic liver failure. The primary goal for this pilot trial is to assess whether the CytoSorb device used in addition to CRRT will be able to significantly reduce bilirubin in the patient blood as compared to the control group treated with CRRT alone (i.e., without extracorporeal hemoadsorption).
Within this trial, CRRT will be initiated early, i.e., in patients with acute kidney injury (AKI) Kidney Disease: Improving Global Outcome (KDIGO) stage 3. For safety assessment, a third group will be assessed without early initiation of CRRT and extracorporeal hemoadsorption. After trial inclusion, all patients will be randomized in a 1:1:1 fashion in one of the study groups.
- Conditions
- Acute-On-Chronic Liver Failure, Renal Failure
- Being tested
- CytoSorb cytokine adsorber, CRRT
- Keywords
- cytokine adsorption, renal replacement therapy, interleukins, cytokines
- Medical subject headings
- Acute-On-Chronic Liver Failure, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytoSorb cytokine adsorberDevice
device for extracorporeal hemoadsorption
CRRTDevice
continuous renal replacement therapy
| Study group | Role | What they receive |
|---|---|---|
| CRRT with cytokine adsorption | Experimental | Patients will be treated with CRRT and extracorporeal hemoadsorption for 72 hours Receives: Device: CytoSorb cytokine adsorber; Device: CRRT |
| CRRT without cytokine adsorption | Experimental | Patients will be treated with CRRT without extracorporeal hemoadsorption for 72 hours Receives: Device: CRRT |
| no CRRT, no cytokine adsorption | No intervention | Patients will not receive CRRT, nor extracorporeal hemoadsorption. CRRT will only be initiated in case of severe electrolyte disorders or unmanageable fluid overload |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum bilirubin
Serum bilirubin after 72 hours
Measured: 72 hours
Secondary outcomes (14)
Survival time
Survival time from baseline
Measured: 30 days
Interleukin-6
Interleukin-6 after 72 hours
Measured: 72 hours
Liver function parameters
Quick/INR, AST, ALT, AP, g-GT
Measured: 72 hours
Blood lactate
Lactate concentration after 72 hours
Measured: 72 hours
CLIF-SOFA-score
CLIF-SOFA-score
Measured: 72 hours
MELD score
MELD score
Measured: 72 hours
SOFA score
SOFA score
Measured: 72 hours
SAPS II
SAPS II
Measured: 72 hours
FIPS score
FIPS score
Measured: 72 hours
Ventilator free days
Ventilator free days (VeFD) in the first 30 days after randomization, where each day on invasive mechanical ventilation (IMV), non-invasive ventilation (NIV), or ECMO is defined as ventilator day. VeFD=0, if the patient dies in the first 30 days after randomization
Measured: 30 days
vasopressor dosage
dosage of epinephrine, norepinephrine, dobutamine, argipressin and terlipressin
Measured: 72 hours
Vasopressor free days
Vasopressor free days (VaFD) in the first 30 days after randomization, where each day with any dose of epinephrine, norepinephrine, dobutamine, argipressin or terlipressin is defined as vasopressor day. VaFD=0, if the patient dies in the first 30 days after randomization
Measured: 30 days
Dialysis free days
Dialysis free days (DFD) in the first 30 days after randomization, where each day on renal replacement therapy (RRT) is defined as dialysis day. DFD=0, if the patient dies in the first 30 days after randomization
Measured: 30 days
Inflammatory biomarkers
A biomarker panel of pro- and anti-inflammatory cytokines (blood samples will be frozen and stored for later analyses, panel will be determined at the time of analysis)
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2021
- Study start25 Oct 2021
- Primary completion31 Dec 2022 (estimated)
- Study completion30 Jan 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute-On-Chronic Liver FailureStudies of the same condition, open and under way.
- 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
- Model description
- In a prallel design participants will be randomly assigned to three different trial groups
- Masking
- None (open label)
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr. Alexander Supady
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Alexander Supady, University Hospital Freiburg
- Investigators
- Alexander Supady, MD, MPH, Principal investigator, University Hospital Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05019352
- Sponsor's protocol ID
- CYTOHEP
- Acronym
- CYTOHEP
- Status last verified
- Oct 2021
- First submitted
- 17 Aug 2021
- Last updated
- 2 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sekandarzad A, Weber E, Prager EP, Graf E, Bettinger D, Wengenmayer T, Supady A. Cytokine adsorption in patients with acute-on-chronic liver failure (CYTOHEP)-a single center, open-label, three-arm, randomized, controlled intervention trial. Trials. 2022 Mar 18;23(1):222. doi: 10.1186/s13063-022-06139-6.
PubMed 35303938
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cytokine Adsorption in Patients With Acute-on-chronic Liver Failure (CYTOHEP) - a Single Center, Open-label, Randomized, Controlled Intervention Trial
- ClinicalTrials.gov ID
- NCT05019352
- Acronym / sponsor ID
- CYTOHEP / CYTOHEP
- Conditions
- Acute-On-Chronic Liver Failure, Renal Failure
- Keywords
- cytokine adsorption, renal replacement therapy, interleukins, cytokines
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Dr. Alexander SupadyUniversity, hospital or other
- Study start
- 25 Oct 2021 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 30 Jan 2023 (estimated)
- First posted
- 24 Aug 2021 (actual)
- 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.
The CYTOHEP study is a prospective, randomized, single center, open-label, controlled intervention trial to assess the benefit of extracorporeal hemoadsorption using the CytoSorb device in patients with acute-on-chronic liver failure. The primary goal for this trial is to assess whether the CytoSorb device used in addition to continuous renal replacement therapy (CRRT) will be able to significantly reduce bilirubin in the patient blood as compared to the control group treated with CRRT alone (i.e., without extracorporeal hemoadsorption).
The rationale for this study is based on considerations about the role of systemic inflammation in acute decompensation of liver cirrhosis and ACLF, in-vitro data of the effectiveness CytoSorb for the removal of molecules with a pathophysiological role in acute-on-chronic liver failure, and recent reports on the successful use of extracorporeal hemoadsorption in combination with CRRT in critically ill patients with acute liver dysfunction.
Detailed description
Liver cirrhosis is a major healthcare problem. The clinical course of cirrhosis can be separated in compensated and decompensated cirrhosis. Patients with compensated cirrhosis are largely asymptomatic and the development of decompensating events is a major hallmark in the course of the disease as median survival decreases from 12 years to less than 2 years. The development of extrahepatic organ complications in decompensated cirrhosis has been identified as a major prognostic milestone and has been described as acute-on-chronic liver failure (ACLF). ACLF is understood as a dynamic process and may evolve within days leading to multi-organ failure with renal failure being the most common organ involvement (56%), followed by liver and coagulation failure (44% and 28%, respectively). ACLF is associated with a high 28-day mortality.
During recent years, systemic inflammation has been recognized as a major driver of hepatic decompensation and progression of liver cirrhosis to ACLF. Importantly, systemic inflammation was described as an important trigger for development of extrahepatic organ failures, such as renal failure, development of hepatopulmonary syndrome, cirrhotic cardiomyopathy and hepatic encephalopathy. Systemic inflammation is particularly relevant in the pathogenesis of acute hepatic decompensation and is also associated with reduced survival. Therefore, elimination of drivers of inflammatory response and inflammatory cytokines in addition to established therapeutic approaches aiming at a reduction of bacterial translocation and mitigation of portal hypertension may help control excessive inflammatory activity and thus support hepatic recompensation. Previous in-vitro examinations and studies in non-cirrhotic inflammatory disorders have shown that proinflammatory cytokines and other factors can effectively be removed by extracorporeal hemoadsorption in the CytoSorb adsorber.
The CYTOHEP study is designed as a prospective, randomized, single center, open-label, controlled intervention trial to assess the benefit of extracorporeal hemoadsorption using the CytoSorb device in patients with acute-on-chronic liver failure. The primary goal for this pilot trial is to assess whether the CytoSorb device used in addition to CRRT will be able to significantly reduce bilirubin in the patient blood as compared to the control group treated with CRRT alone (i.e., without extracorporeal hemoadsorption).
Within this trial, CRRT will be initiated early, i.e., in patients with acute kidney injury (AKI) Kidney Disease: Improving Global Outcome (KDIGO) stage 3. For safety assessment, a third group will be assessed without early initiation of CRRT and extracorporeal hemoadsorption. After trial inclusion, all patients will be randomized in a 1:1:1 fashion in one of the study groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- In a prallel design participants will be randomly assigned to three different trial groups
| Arm | Type | Receives |
|---|---|---|
| CRRT with cytokine adsorption | Experimental | Device: CytoSorb cytokine adsorber, Device: CRRTPatients will be treated with CRRT and extracorporeal hemoadsorption for 72 hours |
| CRRT without cytokine adsorption | Experimental | Device: CRRTPatients will be treated with CRRT without extracorporeal hemoadsorption for 72 hours |
| no CRRT, no cytokine adsorption | No intervention | –Patients will not receive CRRT, nor extracorporeal hemoadsorption. CRRT will only be initiated in case of severe electrolyte disorders or unmanageable fluid overload |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- adult patients (≥ 18 years) admitted to the University Medical Center Freiburg, Germany
- acute-on-chronic liver failure (ACLF) WITH acute kidney injury according to Kidney Disease: Improving Global Outcome (KDIGO) criteria stage 3 (≥ 3-fold increase of serum creatinine OR increase of serum creatinine to ≥ 4 mg/dl OR urine output ≤ 0.3 ml/kg/h for ≥ 24 hours OR anuria for ≥ 12 hours) AND serum bilirubin ≥ 5 mg/dl
Key exclusion criteria (6 listed)
- known patient will against participation in the study or against the measures applied in the study
- a decision made prior to inclusion to stop further treatment of the patient within the next 24 hours
- no complete remission of malignancy including hepatocellular carcinoma within the past 12 months
- patients on the waiting list for liver transplant or the potential option for being listed for liver transplant within the next 6 months
- liver cirrhosis in patients after liver transplantation
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 |
|---|---|---|
| CytoSorb cytokine adsorberdevice for extracorporeal hemoadsorption | Device | CRRT with cytokine adsorption |
| CRRTcontinuous renal replacement therapy | Device | CRRT with cytokine adsorption, CRRT without cytokine adsorption |
Primary outcome
Serum bilirubin
Time frame: 72 hours
Serum bilirubin after 72 hours
14 secondary outcomes
Survival time
Time frame: 30 days
Interleukin-6
Time frame: 72 hours
Liver function parameters
Time frame: 72 hours
Blood lactate
Time frame: 72 hours
CLIF-SOFA-score
Time frame: 72 hours
MELD score
Time frame: 72 hours
SOFA score
Time frame: 72 hours
SAPS II
Time frame: 72 hours
FIPS score
Time frame: 72 hours
Ventilator free days
Time frame: 30 days
vasopressor dosage
Time frame: 72 hours
Vasopressor free days
Time frame: 30 days
Dialysis free days
Time frame: 30 days
Inflammatory biomarkers
Time frame: 72 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2021.
- Derived from this study: PubMed 35303938Sekandarzad A, Weber E, Prager EP, Graf E, Bettinger D, Wengenmayer T, Supady A. Cytokine adsorption in patients with acute-on-chronic liver failure (CYTOHEP)-a single center, open-label, three-arm, randomized, controlled intervention trial. Trials. 2022 Mar 18;23(1):222. doi: 10.1186/s13063-022-06139-6.
- Individual participant dataSharing planned: No
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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.
Alexander Supady, MD, MPH principal investigator
University Hospital Freiburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CytoSorb cytokine adsorber and CRRT in people with Acute-On-Chronic Liver Failure and Renal Failure, run by Dr. Alexander Supady at 1 site in Germany.
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 2 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 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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.
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 Alexander Supady, MD, MPH (+49761270 ext. 34010, alexander.supady@uniklinik-freiburg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum bilirubin (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05019352, which also lists 1 linked publication.
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 2 Nov 2021.