Cirrhosis, LiverPhase 3PLEXARNCT04051437
Plasma Exchange in Acute on Chronic Liver Failure
A Phase 3 study testing Plasma exchange and Standard medical treatment in people with Cirrhosis, Liver and Acute-On-Chronic Liver Failure, run by Asian Institute of Gastroenterology, India.
Trial summary
Acute on chronic liver failure (ACLF) is a distinct syndrome in patients with chronic liver disease with rapid clinical deterioration and has high short term mortality within one month.Despite aggressive clinical care, only half of the patients could survive an episode of ACLF. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cirrhosis, Liver, Acute-On-Chronic Liver Failure
- What is being tested?
- Plasma exchange and Standard medical treatment
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- No sites listed yet
- Study dates
- 15 Aug 2019to 31 Mar 2020
- Phase
- Phase 3
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with ACLF as per APASL criteria with AARC score of ≥8
Who cannot join
- Uncontrolled sepsis
- Septic shock requiring inotropes despite fluid resuscitation
- Active or recent bleeding (unless controlled for >48 hours).
- Severe thrombocytopenia (≤20×10^9/L)
- Acute kidney injury with Creatinine > 2 or the need of RRT
- Respiratory failure (Severe ARDS)
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- Chronic kidney disease
- Hepatocellular carcinoma outside Milan criteria (1 nodule ≤5 cm or 3 nodules ≤3 cm)
- HIV infection
- Pregnancy
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Therapeutic Plasma Exchange in Patients With Acute on Chronic Liver Failure: A Randomized Controlled Trial (PLEXAR)
Acute on chronic liver failure (ACLF) is a distinct syndrome in patients with chronic liver disease with rapid clinical deterioration and has high short term mortality within one month.Despite aggressive clinical care, only half of the patients could survive an episode of ACLF. The investigators hypothesized that the early treatment with therapeutic plasma exchange with plasma and albumin in ACLF patients might improve overall survival in carefully selected patients by removing cytokines, chemokines and toxic substances.
Read the detailed description
Acute on chronic liver failure (ACLF) lacks a consensus definition and definitive management approaches. The various management strategies include treatment of acute insult, support of multiple organ systems and disease-specific medications such as antivirals for hepatitis B, steroids for alcoholic hepatitis, and autoimmune hepatitis. Despite aggressive clinical care, only half of the patients could survive an episode of ACLF. ACLF is a dynamic condition and has specific time-related disease course. Majority of patients of the patients attain their final grade of ACLF between 3 rd and 7th day and makes it an ideal time to assess the prognosis. Recently, liver transplantation option also explored in patients not responding to standard medical care and appeared promising. Early liver transplantation is considered if the baseline model for end-stage liver disease (MELD) score > 28, Asia pacific association for the study of the liver (APASL) ACLF Research Consortium (AARC) score of > 10, advanced hepatic encephalopathy in the absence of organ failures or overt sepsis. However, liver transplantation is feasible only in 25% cases and approximately 67% waitlist mortality. Treating ACLF patients early in the disease course, i.e., window period, may prevent multiorgan dysfunction and improve outcomes. Therefore, these alternative modalities can act as bridging to liver transplantation and hasten the spontaneous liver regeneration and hence, transplant-free recovery in some patients.
Plasma exchange has been shown to reduce cytokines, inflammatory mediators, and damage-associated molecular patterns. The early experience of therapeutic plasma exchange in patients with hepatitis B ACLF shows a survival benefit compared to standard of care. Changes in albumin quantity and quality are noted in patients with cirrhosis. An increase in oxidized albumin, ischemia-modified albumin, and albumin dimerization is observed ACLF patients and changes are more pronounced compared to cirrhotic patients. These changes are well correlated with short and long term mortality.
Hence the investigators hypothesized that the early treatment with therapeutic plasma exchange with plasma and albumin in ACLF patients improves overall survival in carefully selected patients.
- Conditions
- Cirrhosis, Liver, Acute-On-Chronic Liver Failure
- Being tested
- Plasma exchange, Standard medical treatment
- Keywords
- Plasma exchange, Acute on chronic liver failure
- Medical subject headings
- Liver Cirrhosis, Acute-On-Chronic Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma exchangeProcedure or surgery
During each plasma exchange session 3-4lt (1.2-1.3 times of plasma volume) of plasma will be exchanged with fresh frozen plasma and 5% albumin. Plasma exchange session will be done on an alternate day to a maximum of 5 procedures. PLEX will be discontinued if the patients Shows sustained clinical improvement, Receive liver transplantation, Refuses further PLEX session No improvement in clinical condition Intolerant to PLEX procedure
Standard medical treatmentDrug
The consented patients will receive standard medical treatment which includes adequate nutrition (35-45 Kcal/Kg with 1.5gm/Kg protein) diuretics, anti HE measures, appropriate antibiotics for infections,tablet entecavir 0.5 mg once daily for hepatitis B, and steroids for autoimmune hepatitis.
| Study group | Role | What they receive |
|---|---|---|
| Plasma exchange | Experimental | The consented patients will receive standard medical management with sessions of single volume plasma exchange with fresh frozen plasma and 5% human albumin.Plasma exchange session will be done on an alternate day to a maximum of 5 procedures. Receives: Procedure: Plasma exchange |
| Standard medical treatment | Active comparator | The consented patients will receive standard medical treatment which includes adequate nutrition (35-45 Kcal/Kg with 1.5gm/Kg protein) diuretics, anti HE measures, appropriate antibiotics for infections, entecavir 0.5 mg once daily for hepatitis B, and steroids for autoimmune hepatitis. Receives: Drug: Standard medical treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Measured: 90 days
Secondary outcomes (4)
Transplant free survival
Measured: 90 days
Development of organ dysfunction
Measured: 28 days
Development of cirrhosis complications
Measured: 28 days
Improvement in Model for end stage liver disease score
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 posted9 Aug 2019
- Study start15 Aug 2019 (estimated)
- Primary completion31 Mar 2020 (estimated)
- Study completion31 Mar 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cirrhosis, LiverStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Asian Institute of Gastroenterology, India
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Pramod Kumar, Asian Institute of Gastroenterology, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04051437
- Sponsor's protocol ID
- AIG/IEC34/07.2019-08
- Acronym
- PLEXAR
- Status last verified
- Aug 2019
- First submitted
- 3 Aug 2019
- Last updated
- 9 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Plasma Exchange in Patients With Acute on Chronic Liver Failure: A Randomized Controlled Trial (PLEXAR)
- ClinicalTrials.gov ID
- NCT04051437
- Acronym / sponsor ID
- PLEXAR / AIG/IEC34/07.2019-08
- Conditions
- Cirrhosis, Liver, Acute-On-Chronic Liver Failure
- Keywords
- Plasma exchange, Acute on chronic liver failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Asian Institute of Gastroenterology, IndiaUniversity, hospital or other
- Study start
- 15 Aug 2019 (estimated)
- Primary completion
- 31 Mar 2020 (estimated)
- Study completion
- 31 Mar 2020 (estimated)
- First posted
- 9 Aug 2019 (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.
Acute on chronic liver failure (ACLF) is a distinct syndrome in patients with chronic liver disease with rapid clinical deterioration and has high short term mortality within one month.Despite aggressive clinical care, only half of the patients could survive an episode of ACLF. The investigators hypothesized that the early treatment with therapeutic plasma exchange with plasma and albumin in ACLF patients might improve overall survival in carefully selected patients by removing cytokines, chemokines and toxic substances.
Detailed description
Acute on chronic liver failure (ACLF) lacks a consensus definition and definitive management approaches. The various management strategies include treatment of acute insult, support of multiple organ systems and disease-specific medications such as antivirals for hepatitis B, steroids for alcoholic hepatitis, and autoimmune hepatitis. Despite aggressive clinical care, only half of the patients could survive an episode of ACLF. ACLF is a dynamic condition and has specific time-related disease course. Majority of patients of the patients attain their final grade of ACLF between 3 rd and 7th day and makes it an ideal time to assess the prognosis. Recently, liver transplantation option also explored in patients not responding to standard medical care and appeared promising. Early liver transplantation is considered if the baseline model for end-stage liver disease (MELD) score > 28, Asia pacific association for the study of the liver (APASL) ACLF Research Consortium (AARC) score of > 10, advanced hepatic encephalopathy in the absence of organ failures or overt sepsis. However, liver transplantation is feasible only in 25% cases and approximately 67% waitlist mortality. Treating ACLF patients early in the disease course, i.e., window period, may prevent multiorgan dysfunction and improve outcomes. Therefore, these alternative modalities can act as bridging to liver transplantation and hasten the spontaneous liver regeneration and hence, transplant-free recovery in some patients.
Plasma exchange has been shown to reduce cytokines, inflammatory mediators, and damage-associated molecular patterns. The early experience of therapeutic plasma exchange in patients with hepatitis B ACLF shows a survival benefit compared to standard of care. Changes in albumin quantity and quality are noted in patients with cirrhosis. An increase in oxidized albumin, ischemia-modified albumin, and albumin dimerization is observed ACLF patients and changes are more pronounced compared to cirrhotic patients. These changes are well correlated with short and long term mortality.
Hence the investigators hypothesized that the early treatment with therapeutic plasma exchange with plasma and albumin in ACLF patients improves overall survival in carefully selected patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Plasma exchange | Experimental | Procedure: Plasma exchangeThe consented patients will receive standard medical management with sessions of single volume plasma exchange with fresh frozen plasma and 5% human albumin.Plasma exchange session will be done on an alternate day to a maximum of 5 procedures. |
| Standard medical treatment | Active comparator | Drug: Standard medical treatmentThe consented patients will receive standard medical treatment which includes adequate nutrition (35-45 Kcal/Kg with 1.5gm/Kg protein) diuretics, anti HE measures, appropriate antibiotics for infections, entecavir 0.5 mg once daily for hepatitis B, and steroids for autoimmune hepatitis. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients diagnosed with ACLF as per APASL criteria with AARC score of ≥8
Key exclusion criteria (10 listed)
- Uncontrolled sepsis
- Septic shock requiring inotropes despite fluid resuscitation
- Active or recent bleeding (unless controlled for >48 hours).
- Severe thrombocytopenia (≤20×10^9/L)
- Acute kidney injury with Creatinine > 2 or the need of RRT
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 |
|---|---|---|
| Plasma exchangeDuring each plasma exchange session 3-4lt (1.2-1.3 times of plasma volume) of plasma will be exchanged with fresh frozen plasma and 5% albumin. Plasma exchange session will be done on an alternate day to a maximum of 5 procedures. PLEX will be discontinued if the patients Shows sustained clinical improvement, Receive liver transplantation, Refuses further PLEX session No improvement in clinical condition Intolerant to PLEX procedure | Procedure or surgery | Plasma exchange |
| Standard medical treatmentThe consented patients will receive standard medical treatment which includes adequate nutrition (35-45 Kcal/Kg with 1.5gm/Kg protein) diuretics, anti HE measures, appropriate antibiotics for infections,tablet entecavir 0.5 mg once daily for hepatitis B, and steroids for autoimmune hepatitis. | Drug | Standard medical treatment |
Primary outcome
Overall Survival
Time frame: 90 days
4 secondary outcomes
Transplant free survival
Time frame: 90 days
Development of organ dysfunction
Time frame: 28 days
Development of cirrhosis complications
Time frame: 28 days
Improvement in Model for end stage liver disease score
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 9 Aug 2019.
- 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.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Plasma exchange and Standard medical treatment in people with Cirrhosis, Liver and Acute-On-Chronic Liver Failure, run by Asian Institute of Gastroenterology, 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 10 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 9 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Pramod Kumar, MD (+91-9814933544, dapramod@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 90 days). 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 9 Aug 2019.