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NCT Number: NCT06698991

Daily Versus Alternate Day Plasma Exchange in Wilson Disease With Acute Liver Failure in Children

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.

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Key information

Conditions

Acute Liver Failure Basal Ganglia Diseases Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Hepatic Insufficiency Hepatolenticular Degeneration Heredodegenerative Disorders, Nervous System Liver Diseases Liver Failure Liver Failure, Acute Metabolic Diseases Metabolism, Inborn Errors Metal Metabolism, Inborn Errors Movement Disorders Nervous System Diseases Neurodegenerative Diseases Nutritional and Metabolic Diseases Wilson Disease

Age range

3 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location contact

Dr Sanjeevani Kaul, MD

CONTACT

[email protected]

01146300000

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Wilson disease with New Wilson Index of ≥ 11 and INR ≥ 2.5
  • Children aged 3 years to 18 years

Exclusion criteria

  • 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

Treatment and study plan

Plasma Exchange

Biological
  • 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 Treatment

Other

Standard Medical Treatment

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. Comparison of overall and native liver survival at day 90 between the two groups

    Time frame: 90 days

  3. Comparison of change in dialysate copper levels at the end of 3rd session between both groups.

    Time frame: 1 week

  4. Comparison of total number of sessions of plasma exchange between both groups as on day 28.

    Time frame: Day 28

  5. Comparison of AST in U/L, ALT in U/L at end of 3rd plasma exchange compared to baseline.

    Time frame: 1 week

  6. Comparison of corrected reticulocyte count (percentage) at end of 3rd plasma exchange compared to baseline.

    Time frame: 1 week

  7. Comparison of International Normalised Ratio (INR) at end of 3rd plasma exchange compared to baseline.

    Time frame: 1 week

  8. Comparison of bilirubin (mg/dL) at end of 3rd plasma exchange compared to baseline.

    Time frame: 1 week

  9. Comparison of albumin (mg/dL) at end of 3rd plasma exchange compared to baseline.

    Time frame: 1 week

  10. Comparison of serious adverse events as defined by CTCAE criteria in both the groups.

    Time frame: 90 days

Study contacts

Contact information is provided by the study sponsor or research team.

Dr Sanjeevani Kaul, MD

CONTACT

[email protected]

01146300000

Sponsors and collaborators

Lead sponsor

Institute of Liver and Biliary Sciences, India

Other

Registry information

Official study title

Daily Versus Alternate Day Plasma Exchange in Wilson Disease With Acute Liver Failure in Children: A Randomized Controlled Trial

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Nov 21, 2024
Registry last updated
Nov 21, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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