A Trial Of Intravenous N-Acetylcysteine In The Management Of Antituberculous Drug-Induced Hepatitis

NCT02182167 | Completed Phase 2 DMC

• 2 other identifiers: 20130808DOH-27-0414-4719.
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 2

Brief Summary

We will conduct a randomized placebo controlled trial to determine whether administration of intravenous (IV) NAC to participants with TB DIH, in dosages similar to that used in paracetamol poisoning, can improve recovery from hepatotoxicity.

Conditions

Drug-Induced Liver Injury

Keywords

Drug Induced Hepatitis (DIH); Toxic Liver; Drug Induced Liver Injury (DILI)

Outcome Measures

Primary Outcomes (1)

• ALT normalisation

  To determine the effect of IV NAC on the time to normalization of liver function in patients with TB DIH

  up to 8 weeks

Secondary Outcomes (6)

• Duration of hospitalization

  up to 8 weeks

• Recovery from liver failure

  up to 8 weeks

• All-cause mortality

  up to 8 weeks

• Adverse Events

  up to 8 weeks

• TB Drug Rechallenge

  up to 8 weeks

Other Outcomes (1)

• Biomarkers

Study Arms (2)

IV NAC

EXPERIMENTAL

Participants will receive IV N-acetylcysteine or placebo. The dosing regimen is based on the regimens used in paracetamol poisoning . Initial dose: 150 mg/kg body mass of N-acetylcysteine/WFI infused in 200 mL of 5% dextrose intravenously over 60 minutes, followed by continuous infusion: 50 mg/kg body mass in 500 mL of 5% dextrose over next 4 hours, followed by 100 mg/kg body mass in 1 litre of 5% dextrose over 16 hours.

Drug: IV N-acetylcysteine (NAC)

Placebo

PLACEBO COMPARATOR

Water

Drug: Water

Interventions

IV N-acetylcysteine (NAC) DRUG

Also known as: Paradote

IV NAC

Water DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults \> 18 years old
• Diagnosed with pulmonary or extrapulmonary tuberculosis based on symptoms, radiological features and/or laboratory evidence.
• On first line antituberculous therapy
• Diagnosed with TB DIH

You may not qualify if:

• Patients with a diagnosis of acute viral hepatitis based on a positive anti-HAV, IgM, anti- HBcIgM, or confirmed hepatitis C infection
• Patients known to be asthmatic

Sponsors & Collaborators

• University of Cape Town: lead
• Medical Research Council, South Africa: collaborator

Study Sites (2)

Groote Schuur Hospital

Cape Town, Western Province, 7925, South Africa

Location

New Somerset Hospital

Cape Town, Western Province, 8005, South Africa

Location

MeSH Terms

Conditions

Chemical and Drug Induced Liver Injury

Interventions

Acetylcysteine; Water

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Karen Cohen

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Karen Cohen

Study Record Dates

• First Submitted: June 18, 2014
• First Posted: July 8, 2014
• Study Start: May 1, 2014
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: February 19, 2019

Record last verified: 2019-02

Locations

ZA (2)