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

NCT06698991 | Not Yet Recruiting

• 1 other identifier: ILBS-ALF-07
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Acute Liver Failure; Wilson Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Day 7

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

  90 days

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

  1 week

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

  Day 28

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

  1 week

Study Arms (2)

Daily plasma exchange + SMT

EXPERIMENTAL

(Maximum 3+1 sessions during a period of 7 days)

Biological: Plasma Exchange; Other: Standard Medical Treatment

Alternate day therapeutic plasma exchange + SMT

ACTIVE COMPARATOR

Alternate day therapeutic plasma exchange + SMT

Biological: Plasma Exchange; Other: Standard Medical Treatment

Interventions

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

Alternate day therapeutic plasma exchange + SMT; Daily plasma exchange + SMT

Standard Medical Treatment OTHER

Standard Medical Treatment

Alternate day therapeutic plasma exchange + SMT; Daily plasma exchange + SMT

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences

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

Location

MeSH Terms

Conditions

Liver Failure, Acute; Hepatolenticular Degeneration

Interventions

Plasma Exchange

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Central Study Contacts

Dr Sanjeevani Kaul, MD

CONTACT

01146300000; sanjeevani.kaul07@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2024
• First Posted: November 21, 2024
• Study Start: November 10, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 21, 2024

Record last verified: 2024-11

Locations

IN (1)