Drug-Induced Liver InjuryPhase 2/3NAC in TB DIHNCT02182167
A Trial Of Intravenous N-Acetylcysteine In The Management Of Antituberculous Drug-Induced Hepatitis
A Phase 2/3 study testing IV N-acetylcysteine (NAC) and Water in people with Drug-Induced Liver Injury, run by University of Cape Town at 2 sites in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug-Induced Liver Injury
- What is being tested?
- IV N-acetylcysteine (NAC) and Water
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 2 sitesSouth Africa
- Study dates
- May 2014to Feb 2019
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
South Africa2 sites
Groote Schuur Hospital
Cape Town, Western Province, 7925
New Somerset Hospital
Cape Town, Western Province, 8005
About this study
Official title: A Randomised Controlled Trial of Intravenous N-acetylcysteine in the Management of Antituberculous Drug-induced Hepatitis
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.
Read the detailed description
South Africa has a huge tuberculosis (TB) disease burden, with 948 per 100 000 people diagnosed with TB in 2008. TB drug induced hepatitis (DIH) is a common adverse effect of TB therapy that causes significant patient morbidity and prolonged hospital stays. N-Acetylcysteine (NAC) has been extensively studied and used for many years in the treatment of paracetamol-induced hepatotoxicity, with good evidence of efficacy and safety. NAC has also been used in other forms of liver injury and drug toxicity. It has not previously been used in the management of TB DIH.
We will screen all patients with clinical hepatitis on TB treatment admitted to New Somerset and Groote Schuur hospitals and aim to recruit 100 participants over 3 years. We will randomise 50 participants to receive an IV loading dose of 150mg/kg of NAC over 60 minutes followed by 50mg/kg IV over 4 hours by continuous infusion and finally 100mg/kg IV over 16 hours. Fifty participants will be randomised to receive placebo. The primary outcome will be time to normalisation of liver function (ALT<100). We will also determine the effect of NAC on duration of hospitalization, rate of recovery from liver failure, all cause mortality, and describe adverse effects of IV NAC in this patient population.
- Conditions
- Drug-Induced Liver Injury
- Being tested
- IV N-acetylcysteine (NAC), Water
- Keywords
- Drug Induced Hepatitis (DIH), Toxic Liver, Drug Induced Liver Injury (DILI)
- Medical subject headings
- Chemical and Drug Induced Liver Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV N-acetylcysteine (NAC)Drug
Also called Paradote
WaterDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: IV N-acetylcysteine (NAC) |
| Placebo | Placebo comparator | Water Receives: Drug: Water |
What is being measured
The primary outcome is the main question the study is designed to answer.
ALT normalisation
To determine the effect of IV NAC on the time to normalization of liver function in patients with TB DIH
Measured: up to 8 weeks
Secondary outcomes (6)
Duration of hospitalization
To determine the effect of IV NAC on duration of hospitalization
Measured: up to 8 weeks
Recovery from liver failure
To determine the effect of IV NAC on the rate of recovery from liver failure
Measured: up to 8 weeks
All-cause mortality
To determine the effect of IV NAC on all-cause mortality in patients with TB DIH
Measured: up to 8 weeks
Adverse Events
To determine the adverse event profile of IV NAC when administered to patients with TB DIH
Measured: up to 8 weeks
TB Drug Rechallenge
To determine the effect of IV NAC on success of TB drug rechallenge.
Measured: up to 8 weeks
Rechallenge duration
To determine the effect of IV NAC on duration of rechallenge
Measured: up to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2014 (estimated)
- Study startMay 2014
- Primary completionFeb 2019
- Study completionFeb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug-Induced Liver InjuryStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, South Africa
- Responsible party
- Principal investigator, Dr Karen Cohen, University of Cape Town
- Investigators
- Karen Cohen, Principal investigator, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02182167
- Sponsor's protocol ID
- 20130808
- Other IDs
- DOH-27-0414-4719.
- Acronym
- NAC in TB DIH
- Status last verified
- Feb 2019
- First submitted
- 18 Jun 2014
- Last updated
- 19 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial of Intravenous N-acetylcysteine in the Management of Antituberculous Drug-induced Hepatitis
- ClinicalTrials.gov ID
- NCT02182167
- Acronym / sponsor ID
- NAC in TB DIH / 20130808
- Conditions
- Drug-Induced Liver Injury
- Keywords
- Drug Induced Hepatitis (DIH), Toxic Liver, Drug Induced Liver Injury (DILI)
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Collaborators
- Medical Research Council, South Africa
- Study start
- May 2014 (actual)
- Primary completion
- Feb 2019 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 8 Jul 2014 (estimated)
- 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.
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.
Detailed description
South Africa has a huge tuberculosis (TB) disease burden, with 948 per 100 000 people diagnosed with TB in 2008. TB drug induced hepatitis (DIH) is a common adverse effect of TB therapy that causes significant patient morbidity and prolonged hospital stays. N-Acetylcysteine (NAC) has been extensively studied and used for many years in the treatment of paracetamol-induced hepatotoxicity, with good evidence of efficacy and safety. NAC has also been used in other forms of liver injury and drug toxicity. It has not previously been used in the management of TB DIH.
We will screen all patients with clinical hepatitis on TB treatment admitted to New Somerset and Groote Schuur hospitals and aim to recruit 100 participants over 3 years. We will randomise 50 participants to receive an IV loading dose of 150mg/kg of NAC over 60 minutes followed by 50mg/kg IV over 4 hours by continuous infusion and finally 100mg/kg IV over 16 hours. Fifty participants will be randomised to receive placebo. The primary outcome will be time to normalisation of liver function (ALT<100). We will also determine the effect of NAC on duration of hospitalization, rate of recovery from liver failure, all cause mortality, and describe adverse effects of IV NAC in this patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV NAC | Experimental | Drug: IV N-acetylcysteine (NAC)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. |
| Placebo | Placebo comparator | Drug: WaterWater |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- 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
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 |
|---|---|---|
| IV N-acetylcysteine (NAC)Also: Paradote | Drug | IV NAC |
| Water | Drug | Placebo |
Primary outcome
ALT normalisation
Time frame: up to 8 weeks
To determine the effect of IV NAC on the time to normalization of liver function in patients with TB DIH
6 secondary outcomes
Duration of hospitalization
Time frame: up to 8 weeks
Recovery from liver failure
Time frame: up to 8 weeks
All-cause mortality
Time frame: up to 8 weeks
Adverse Events
Time frame: up to 8 weeks
TB Drug Rechallenge
Time frame: up to 8 weeks
Rechallenge duration
Time frame: up to 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
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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.
Karen Cohen principal investigator
University of Cape Town
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing IV N-acetylcysteine (NAC) and Water in people with Drug-Induced Liver Injury, run by University of Cape Town at 2 sites in South Africa.
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 4 inclusion and 2 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: finished, as of the sponsor's last update on 19 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ALT normalisation (time frame: up to 8 weeks). 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 19 Feb 2019.