Acute-On-Chronic Liver FailurePhase 4NCT04243655
Use of HA 330-II for Hemofiltration in Patients With ALF as a Bridge to Liver Transplantation .
A Phase 4 study testing HA 330-II and Standard medical treatment (SMT) in people with Acute-On-Chronic Liver Failure, run by Asian Institute of Gastroenterology, India at 1 site in India.
Trial summary
ALF (ALF) is defined by three criteria: (1) rapid development of hepatocellular dysfunction (jaundice, coagulopathy), (2) hepatic encephalopathy, and (3) absence of a prior history of liver disease. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute-On-Chronic Liver Failure
- What is being tested?
- HA 330-II and Standard medical treatment (SMT)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteIndia
- Study dates
- 30 Dec 2019to 31 Dec 2020
- Phase
- Phase 4
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute Liver Failure patients with SIRS and Hepatic Encephalopathy, without hyperbilirubinemia.
Who cannot join
- Patients with age less than 18 years or more than 65 years
- Extremely moribund patients with an expected life expectancy of less than 24 hours or with poor prognosis
- With poor blood clotting function and PTA <30%.
- Active Bleed
- Chronic heart, lung or kidney disease
- Malignant tumors including liver cancer
- Past history of organ transplantation
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Asian Institute Of Gastroenterology
Hyderabad, Telangana, 500032
Mithun Sharma, MD
Padaki N Rao, MD DM
About this study
Official title: Use of HA 330-II for Hemofiltration in Patients With Acute Liver Failure as a Bridge to Liver Transplantation: Clinical Evaluation Protocol.
ALF (ALF) is defined by three criteria: (1) rapid development of hepatocellular dysfunction (jaundice, coagulopathy), (2) hepatic encephalopathy, and (3) absence of a prior history of liver disease.
Interval between onset of acute hepatic injury (jaundice) and onset of liver failure (encephalopathy with or without coagulopathy) in such patients (icterus-encephalopathy interval; IEI) has been described to be between 4 weeks (Indian definition) to 24 weeks (AASLD-ALF study group). Further, due to the diverse natural course, ALF has been sub-classified as hyperacute (IEI ≤ 7 day), acute (IEI ≤ 4 weeks) and sub-acute ALF (IEI ≥ 5 week to ≤12 weeks) by British authors.
Read the detailed description
Since the 1960s, Liver Transplantation (LT) has emerged as a cornerstone intervention to cure liver failure. Mortality in patients with liver failure who cannot be rescued with Liver Transplantation remains high despite improvements in supportive care.
Artificial Liver Support System (ALSS) in ALF aim to remove excess inflammatory cytokines and attenuate inflammatory response, to remove albumin-bound and water-soluble toxins, to restore and preserve hepatic function and mitigate or limit the progression of multiorgan failure while hepatic recovery or liver transplant occurs. ALSS may also provide benefit in instances where LT is contraindicated.
The following beneficial effects have been documented with ALSS in ALF patients: improvement of jaundice, amelioration of hemodynamic instability, improvement of hepatic encephalopathy, SOFA score and survival.
HA 330-II is a broad-spectrum adsorbent made of neutral macroporous resin, removes toxins such as Inflammatory mediators (IL-1, IL-6, IL-8 \& TNF-α) along with hepatic toxins such as phenol, mercaptan, aromatic amino acids, false neurotransmitters and indirectly ammonia by improving liver function recovery. However, this indirect ammonia removal with HA 330-II is insignificant. By removing excess inflammatory cytokines and attenuating uncontrolled immune response, HA 330-II prevents worsening of encephalopathy, improves liver function recovery and improves prognosis.
- Conditions
- Acute-On-Chronic Liver Failure
- Being tested
- HA 330-II, Standard medical treatment (SMT)
- Medical subject headings
- Acute-On-Chronic Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HA 330-IIDevice
One unit for 2-4 hours treatment, for 3 consecutive days
Standard medical treatment (SMT)Drug
SMT as per patients requirement- Management of cerebral edema/intracranial hypertension: prophylactic antibiotics, administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure, volume replacement and pressor support (noradrenaline, doubutamine, dopamine) as needed, NAC and correction of metabolic parameters.
| Study group | Role | What they receive |
|---|---|---|
| Hemoperfusion treatment with HA 330-II | Experimental | Hemoperfusion treatment with HA 330-II, one unit for 2-4 hours treatment, for 3 consecutive days along with SMT as per patients requirement. Receives: Device: HA 330-II; Drug: Standard medical treatment (SMT) |
| Standard medical treatment (SMT) | Active comparator | SMT as per patients requirement- Management of cerebral edema/intracranial hypertension: prophylactic antibiotics, administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure, volume replacement and pressor support (noradrenaline, doubutamine, dopamine) as needed, NAC and correction of metabolic parameters. Receives: Drug: Standard medical treatment (SMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of HA 330-II to prolong liver-transplantation free survival.
The length of survival time after first hemofiltration treatment during the follow-up period.
Measured: Up to 30 Days
Secondary outcomes (4)
Change in Systemic inflammatory response syndrome (SIRS) score.
To assess efficacy of treatment.
Measured: Up to 7 Days, post hemofiltration
Change in Acute Physiology and Chronic Health Evaluation (APACHE-II) score.
To assess efficacy of treatment.
Measured: Up to 7 Days, post hemofiltration
Change in sequential organ failure assessment (SOFA) score.
To assess efficacy of treatment.
Measured: Up to 7 Days, post hemofiltration
Change in chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score.
To assess efficacy of treatment.
Measured: Up to 7 Days, post hemofiltration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2020
- Study start30 Dec 2019
- Primary completionOct 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute-On-Chronic Liver FailureStudies of the same condition, open and under way.
- More trials run by Asian Institute of Gastroenterology, IndiaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Hemoperfusion treatment with HA 330-II, one unit for 2-4 hours treatment, for 3 consecutive days along with standard medical treatment (SMT) as per patients requirement.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Asian Institute of Gastroenterology, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mithun Sharma, Principal investigator, AIG Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04243655
- Sponsor's protocol ID
- AIG-G/ALFLD
- Status last verified
- Jan 2020
- First submitted
- 17 Jan 2020
- Last updated
- 28 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure. Hepatology. 2000 Oct;32(4 Pt 1):734-9. doi: 10.1053/jhep.2000.17687.
PubMed 11003617Lee KC, Stadlbauer V, Jalan R. Extracorporeal liver support devices for listed patients. Liver Transpl. 2016 Jun;22(6):839-48. doi: 10.1002/lt.24396.
PubMed 26785141Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC, Triantafyllou E, Bernal W, Auzinger G, Shawcross D, Eefsen M, Bjerring PN, Clemmesen JO, Hockerstedt K, Frederiksen HJ, Hansen BA, Antoniades CG, Wendon J. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol. 2016 Jan;64(1):69-78. doi: 10.1016/j.jhep.2015.08.018. Epub 2015 Aug 29.
PubMed 26325537
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of HA 330-II for Hemofiltration in Patients With Acute Liver Failure as a Bridge to Liver Transplantation: Clinical Evaluation Protocol.
- ClinicalTrials.gov ID
- NCT04243655
- Acronym / sponsor ID
- AIG-G/ALFLD
- Conditions
- Acute-On-Chronic Liver Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Asian Institute of Gastroenterology, IndiaUniversity, hospital or other
- Study start
- 30 Dec 2019 (actual)
- Primary completion
- Oct 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 28 Jan 2020 (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.
ALF (ALF) is defined by three criteria: (1) rapid development of hepatocellular dysfunction (jaundice, coagulopathy), (2) hepatic encephalopathy, and (3) absence of a prior history of liver disease.
Interval between onset of acute hepatic injury (jaundice) and onset of liver failure (encephalopathy with or without coagulopathy) in such patients (icterus-encephalopathy interval; IEI) has been described to be between 4 weeks (Indian definition) to 24 weeks (AASLD-ALF study group). Further, due to the diverse natural course, ALF has been sub-classified as hyperacute (IEI ≤ 7 day), acute (IEI ≤ 4 weeks) and sub-acute ALF (IEI ≥ 5 week to ≤12 weeks) by British authors.
Detailed description
Since the 1960s, Liver Transplantation (LT) has emerged as a cornerstone intervention to cure liver failure. Mortality in patients with liver failure who cannot be rescued with Liver Transplantation remains high despite improvements in supportive care.
Artificial Liver Support System (ALSS) in ALF aim to remove excess inflammatory cytokines and attenuate inflammatory response, to remove albumin-bound and water-soluble toxins, to restore and preserve hepatic function and mitigate or limit the progression of multiorgan failure while hepatic recovery or liver transplant occurs. ALSS may also provide benefit in instances where LT is contraindicated.
The following beneficial effects have been documented with ALSS in ALF patients: improvement of jaundice, amelioration of hemodynamic instability, improvement of hepatic encephalopathy, SOFA score and survival.
HA 330-II is a broad-spectrum adsorbent made of neutral macroporous resin, removes toxins such as Inflammatory mediators (IL-1, IL-6, IL-8 \& TNF-α) along with hepatic toxins such as phenol, mercaptan, aromatic amino acids, false neurotransmitters and indirectly ammonia by improving liver function recovery. However, this indirect ammonia removal with HA 330-II is insignificant. By removing excess inflammatory cytokines and attenuating uncontrolled immune response, HA 330-II prevents worsening of encephalopathy, improves liver function recovery and improves prognosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Hemoperfusion treatment with HA 330-II, one unit for 2-4 hours treatment, for 3 consecutive days along with standard medical treatment (SMT) as per patients requirement.
| Arm | Type | Receives |
|---|---|---|
| Hemoperfusion treatment with HA 330-II | Experimental | Device: HA 330-II, Drug: Standard medical treatment (SMT)Hemoperfusion treatment with HA 330-II, one unit for 2-4 hours treatment, for 3 consecutive days along with SMT as per patients requirement. |
| Standard medical treatment (SMT) | Active comparator | Drug: Standard medical treatment (SMT)SMT as per patients requirement- Management of cerebral edema/intracranial hypertension: prophylactic antibiotics, administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure, volume replacement and pressor support (noradrenaline, doubutamine, dopamine) as needed, NAC and correction of metabolic parameters. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Acute Liver Failure patients with SIRS and Hepatic Encephalopathy, without hyperbilirubinemia.
Key exclusion criteria (7 listed)
- Patients with age less than 18 years or more than 65 years
- Extremely moribund patients with an expected life expectancy of less than 24 hours or with poor prognosis
- With poor blood clotting function and PTA <30%.
- Active Bleed
- Chronic heart, lung or kidney disease
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 |
|---|---|---|
| HA 330-IIOne unit for 2-4 hours treatment, for 3 consecutive days | Device | Hemoperfusion treatment with HA 330-II |
| Standard medical treatment (SMT)SMT as per patients requirement- Management of cerebral edema/intracranial hypertension: prophylactic antibiotics, administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure, volume replacement and pressor support (noradrenaline, doubutamine, dopamine) as needed, NAC and correction of metabolic parameters. | Drug | Hemoperfusion treatment with HA 330-II, Standard medical treatment (SMT) |
Primary outcome
Efficacy of HA 330-II to prolong liver-transplantation free survival.
Time frame: Up to 30 Days
The length of survival time after first hemofiltration treatment during the follow-up period.
4 secondary outcomes
Change in Systemic inflammatory response syndrome (SIRS) score.
Time frame: Up to 7 Days, post hemofiltration
Change in Acute Physiology and Chronic Health Evaluation (APACHE-II) score.
Time frame: Up to 7 Days, post hemofiltration
Change in sequential organ failure assessment (SOFA) score.
Time frame: Up to 7 Days, post hemofiltration
Change in chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score.
Time frame: Up to 7 Days, post hemofiltration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2020.
- Background: PubMed 11003617Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure. Hepatology. 2000 Oct;32(4 Pt 1):734-9. doi: 10.1053/jhep.2000.17687.
- Background: PubMed 26785141Lee KC, Stadlbauer V, Jalan R. Extracorporeal liver support devices for listed patients. Liver Transpl. 2016 Jun;22(6):839-48. doi: 10.1002/lt.24396.
- Background: PubMed 26325537Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC, Triantafyllou E, Bernal W, Auzinger G, Shawcross D, Eefsen M, Bjerring PN, Clemmesen JO, Hockerstedt K, Frederiksen HJ, Hansen BA, Antoniades CG, Wendon J. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol. 2016 Jan;64(1):69-78. doi: 10.1016/j.jhep.2015.08.018. Epub 2015 Aug 29.
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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.
Mithun Sharma principal investigator
AIG Hospitals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing HA 330-II and Standard medical treatment (SMT) in people with Acute-On-Chronic Liver Failure, run by Asian Institute of Gastroenterology, India at 1 site in India.
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 1 inclusion and 7 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 28 Jan 2020. 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 India. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Mithun Sharma, MD, DM (08790622655, drmithunsharma@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of HA 330-II to prolong liver-transplantation free survival. (time frame: Up to 30 Days). 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 NCT04243655, which also lists 3 linked publications.
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 28 Jan 2020.