Acute Liver FailureNCT06698991
Daily Versus Alternate Day Plasma Exchange in Wilson Disease With Acute Liver Failure in Children
A study testing Plasma Exchange and Standard Medical Treatment in people with Acute Liver Failure and Wilson Disease, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial summary
Wilson disease in children has a varied presentation. Wilson disease with acute liver failure is associated with very high mortality and morbidity. The standard therapy i.e chelation (with either D- penicillamine or trientene can be used as a temporizing agent to treat the enormous release of copper into the blood… Read more about this study
- Who is it for?
- Ages 3 to 18 years
- Conditions the study is for
- Acute Liver Failure, Wilson Disease
- What is being tested?
- Plasma Exchange and Standard Medical Treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteIndia
- Study dates
- 10 Nov 2024to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 3 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Wilson disease with New Wilson Index of ≥ 11 and INR ≥ 2.5
- Children aged 3 years to 18 years
Who cannot join
- Grade 3 or grade 4 hepatic encephalopathy
- Septic shock
- Disseminated intravascular coagulation
- Marked hemodynamic instability requiring a high dose of vasopressors (norepinephrine >0.5 mcg/kg/min)
- Any severe cardio-pulmonary pre-existing disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
India1 site
Institute of Liver & Biliary Sciences
New Delhi, National Capital Territory of Delhi, 110070
Dr Sanjeevani Kaul, MD, 01146300000, sanjeevani.kaul07@gmail.com
About this study
Official title: Daily Versus Alternate Day Plasma Exchange in Wilson Disease With Acute Liver Failure in Children: A Randomized Controlled Trial
Wilson disease in children has a varied presentation. Wilson disease with acute liver failure is associated with very high mortality and morbidity. The standard therapy i.e chelation (with either D- penicillamine or trientene can be used as a temporizing agent to treat the enormous release of copper into the blood stream; however, substantial removal is not achieved for at least 1 to 3 months. Plasma exchange provides a means of rapid means of removal of copper. As per American Society for Apheresis, TPE in wilson disease with acute liver failure can rapidly remove an average of 20 mg of copper per TPE treatment. Decreased serum copper may decrease hemolysis, prevent progression of kidney failure and provide clinical stabilization. TPE can also remove large molecular weight toxins (aromatic amino acids, ammonia, endotoxins) and other factors, which may be responsible for hepatic coma. The frequency of said TPE is not defined as most evidence is based on case reports and case series.
Copper is highly protein bound and the volume of distribution for copper is large. Under normal conditions, 90-95% of serum copper is ceruloplasmin-bound with the remaining 5-10% being nonceruloplasmin-bound. TPE efficiently removes both ceruloplasmin- and albumin-bound copper. FFP used for exchange can be helpful in treating the associated coagulopathy. TPE has been used as a bridge to liver transplantation as well as seen to improve survival with native liver, the optimum protocol for same remains uncertain.
Read the detailed description
Study population: Children aged 3 to 18 years with Wilson disease (diagnosed as per Leipzig score >=4) with fulminant presentation (as defined by New Wilson Index>= 11 and INR >= 2.5 ).
Adverse effects: Therapeutic plasma exchange has been shown to be safe and effective in improving native liver survival in Wilson disease patients and is currently standard of care in patients with wilson disease with acute liver failure. However, TPE can be associated with risk of adverse events like infections, fluid overload or circulatory insufficiency, hypersensitivity to blood products.
Stopping rule:
- Septic Shock
- Anaphylaxis to blood products
- HE grade3/4
- INR > 5 any time point
- INR >3.5 24 hours after 3 HVP Patients fulfilling criteria 3, 4 and 5 would be listed for liver transplantation. In case of 1, 2 appropriate medical management will be done as per department protocol.
Intervention:
Group 1: Daily plasma exchange + SMT (Maximum 3+1 sessions during a period of 7 days) Group 2: Alternate day therapeutic plasma exchange + SMT
- Conditions
- Acute Liver Failure, Wilson Disease
- Being tested
- Plasma Exchange, Standard Medical Treatment
- Medical subject headings
- Liver Failure, Acute, Hepatolenticular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma ExchangeBiological
- Plasma exchange (1.5 times plasma exchange)
- Blood volume: 80ml/kg
- Plasma volume = Blood volume x (1 - Hematocrit/100)
- TPE volume = 1.5 x plasma volume
- Duration: 4 hours
Standard Medical TreatmentOther
Standard Medical Treatment
| Study group | Role | What they receive |
|---|---|---|
| Daily plasma exchange + SMT | Experimental | (Maximum 3+1 sessions during a period of 7 days) Receives: Biological: Plasma Exchange; Other: Standard Medical Treatment |
| Alternate day therapeutic plasma exchange + SMT | Active comparator | Alternate day therapeutic plasma exchange + SMT Receives: Biological: Plasma Exchange; Other: Standard Medical Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the reduction in NWI (New Wilson Index) between both groups at the end of three sessions of plasma exchange
The New Wilson Index is a composite score containing of bilirubin, albumin, INR, AST, total leucocyte count ranging from minimum score of 0 till maximum of 20 with a higher score correlating with a worse outcome. A score of NWI \>=11 is associated with increased mortality and considered an indication for consideration for liver transplantation in patients with Wilson disease.
Measured: 7 days
Secondary outcomes (10)
Comparison of change in serum and urine copper levels on day 7 after initiation of plasmapheresis as compared to baseline in alternate versus daily plasma exchange group.
Measured: Day 7
Comparison of overall and native liver survival at day 90 between the two groups
Measured: 90 days
Comparison of change in dialysate copper levels at the end of 3rd session between both groups.
Measured: 1 week
Comparison of total number of sessions of plasma exchange between both groups as on day 28.
Measured: Day 28
Comparison of AST in U/L, ALT in U/L at end of 3rd plasma exchange compared to baseline.
Measured: 1 week
Comparison of corrected reticulocyte count (percentage) at end of 3rd plasma exchange compared to baseline.
Measured: 1 week
Comparison of International Normalised Ratio (INR) at end of 3rd plasma exchange compared to baseline.
Measured: 1 week
Comparison of bilirubin (mg/dL) at end of 3rd plasma exchange compared to baseline.
Measured: 1 week
Comparison of albumin (mg/dL) at end of 3rd plasma exchange compared to baseline.
Measured: 1 week
Comparison of serious adverse events as defined by CTCAE criteria in both the groups.
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 posted21 Nov 2024
- Study start10 Nov 2024 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
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 Institute of Liver and Biliary Sciences, 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06698991
- Sponsor's protocol ID
- ILBS-ALF-07
- Status last verified
- Nov 2024
- First submitted
- 16 Nov 2024
- Last updated
- 21 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Daily Versus Alternate Day Plasma Exchange in Wilson Disease With Acute Liver Failure in Children: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06698991
- Acronym / sponsor ID
- ILBS-ALF-07
- Conditions
- Acute Liver Failure, Wilson Disease
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 10 Nov 2024 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 21 Nov 2024 (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.
Wilson disease in children has a varied presentation. Wilson disease with acute liver failure is associated with very high mortality and morbidity. The standard therapy i.e chelation (with either D- penicillamine or trientene can be used as a temporizing agent to treat the enormous release of copper into the blood stream; however, substantial removal is not achieved for at least 1 to 3 months. Plasma exchange provides a means of rapid means of removal of copper. As per American Society for Apheresis, TPE in wilson disease with acute liver failure can rapidly remove an average of 20 mg of copper per TPE treatment. Decreased serum copper may decrease hemolysis, prevent progression of kidney failure and provide clinical stabilization. TPE can also remove large molecular weight toxins (aromatic amino acids, ammonia, endotoxins) and other factors, which may be responsible for hepatic coma. The frequency of said TPE is not defined as most evidence is based on case reports and case series.
Copper is highly protein bound and the volume of distribution for copper is large. Under normal conditions, 90-95% of serum copper is ceruloplasmin-bound with the remaining 5-10% being nonceruloplasmin-bound. TPE efficiently removes both ceruloplasmin- and albumin-bound copper. FFP used for exchange can be helpful in treating the associated coagulopathy. TPE has been used as a bridge to liver transplantation as well as seen to improve survival with native liver, the optimum protocol for same remains uncertain.
Detailed description
Study population: Children aged 3 to 18 years with Wilson disease (diagnosed as per Leipzig score >=4) with fulminant presentation (as defined by New Wilson Index>= 11 and INR >= 2.5 ).
Adverse effects: Therapeutic plasma exchange has been shown to be safe and effective in improving native liver survival in Wilson disease patients and is currently standard of care in patients with wilson disease with acute liver failure. However, TPE can be associated with risk of adverse events like infections, fluid overload or circulatory insufficiency, hypersensitivity to blood products.
Stopping rule:
- Septic Shock
- Anaphylaxis to blood products
- HE grade3/4
- INR > 5 any time point
- INR >3.5 24 hours after 3 HVP Patients fulfilling criteria 3, 4 and 5 would be listed for liver transplantation. In case of 1, 2 appropriate medical management will be done as per department protocol.
Intervention:
Group 1: Daily plasma exchange + SMT (Maximum 3+1 sessions during a period of 7 days) Group 2: Alternate day therapeutic plasma exchange + SMT
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Daily plasma exchange + SMT | Experimental | Biological: Plasma Exchange, Other: Standard Medical Treatment(Maximum 3+1 sessions during a period of 7 days) |
| Alternate day therapeutic plasma exchange + SMT | Active comparator | Biological: Plasma Exchange, Other: Standard Medical TreatmentAlternate day therapeutic plasma exchange + SMT |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Wilson disease with New Wilson Index of ≥ 11 and INR ≥ 2.5
- Children aged 3 years to 18 years
Key exclusion criteria (5 listed)
- Grade 3 or grade 4 hepatic encephalopathy
- Septic shock
- Disseminated intravascular coagulation
- Marked hemodynamic instability requiring a high dose of vasopressors (norepinephrine >0.5 mcg/kg/min)
- Any severe cardio-pulmonary pre-existing 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 |
|---|---|---|
| Plasma Exchange• Plasma exchange (1.5 times plasma exchange) * Blood volume: 80ml/kg * Plasma volume = Blood volume x (1 - Hematocrit/100) * TPE volume = 1.5 x plasma volume * Duration: 4 hours | Biological | Alternate day therapeutic plasma exchange + SMT, Daily plasma exchange + SMT |
| Standard Medical TreatmentStandard Medical Treatment | Other | Alternate day therapeutic plasma exchange + SMT, Daily plasma exchange + SMT |
Primary outcome
To compare the reduction in NWI (New Wilson Index) between both groups at the end of three sessions of plasma exchange
Time frame: 7 days
The New Wilson Index is a composite score containing of bilirubin, albumin, INR, AST, total leucocyte count ranging from minimum score of 0 till maximum of 20 with a higher score correlating with a worse outcome. A score of NWI \>=11 is associated with increased mortality and considered an indication for consideration for liver transplantation in patients with Wilson disease.
10 secondary outcomes
Comparison of change in serum and urine copper levels on day 7 after initiation of plasmapheresis as compared to baseline in alternate versus daily plasma exchange group.
Time frame: Day 7
Comparison of overall and native liver survival at day 90 between the two groups
Time frame: 90 days
Comparison of change in dialysate copper levels at the end of 3rd session between both groups.
Time frame: 1 week
Comparison of total number of sessions of plasma exchange between both groups as on day 28.
Time frame: Day 28
Comparison of AST in U/L, ALT in U/L at end of 3rd plasma exchange compared to baseline.
Time frame: 1 week
Comparison of corrected reticulocyte count (percentage) at end of 3rd plasma exchange compared to baseline.
Time frame: 1 week
Comparison of International Normalised Ratio (INR) at end of 3rd plasma exchange compared to baseline.
Time frame: 1 week
Comparison of bilirubin (mg/dL) at end of 3rd plasma exchange compared to baseline.
Time frame: 1 week
Comparison of albumin (mg/dL) at end of 3rd plasma exchange compared to baseline.
Time frame: 1 week
Comparison of serious adverse events as defined by CTCAE criteria in both the groups.
Time frame: 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2024.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Plasma Exchange and Standard Medical Treatment in people with Acute Liver Failure and Wilson Disease, run by Institute of Liver and Biliary Sciences, 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 2 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: opening soon, as of the sponsor's last update on 21 Nov 2024. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr Sanjeevani Kaul, MD (01146300000, sanjeevani.kaul07@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare the reduction in NWI (New Wilson Index) between both groups at the end of three sessions of plasma exchange (time frame: 7 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 21 Nov 2024.