HepatitisNCT00929786
Anti-tuberculosis (TB) Drug Levels and Hepatotoxicity
An observational study of Hepatitis and Tuberculosis, run by All India Institute of Medical Sciences at 2 sites in India.
Trial summary
The purpose of this study is to evaluate plasma levels of hepatotoxic anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide plus significant metabolites) among patients on antituberculosis treatment (ATT) and compare the same among those who develop drug induced hepatitis on follow up versus those who do not. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Hepatitis, Tuberculosis
- How many people
- 72 participants
- Where
- 2 sitesIndia
- Study dates
- Nov 2007to Jun 2009
- Phase
- Observational
- 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 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Subjects: Patients with diagnosis of CatI/CatIII Tuberculosis attending the out-patient department of the All India Institute of Medical Sciences, New Delhi, will form the study population. Cases - those patients who develop DIH while on regular treatment with anti-TB drugs Controls - age, sex matched patients who do not develop DIH while on regular treatment with anti-TB drugs
Who may be able to join
- Patients diagnosed to be suffering from CatI/CatIII tuberculosis by a physician
- Age: 16-65 years
- Patient having normal baseline Liver function (AST/ALT1 < 50/50, serum bilirubin < 1.5 mg/dl)
Who cannot join
- Patients receiving any other drug known to be metabolized by liver by cytochrome P450 3A4 or P-glycoprotein
- Patients diagnosed to have acute viral hepatitis A, B, C, or E or carrier for HBV \& HCV
- Known HIV positive patients
- Presence of chronic liver disease or renal insufficiency
- Concomitant administration of other potential hepatotoxic drugs (methotrexate, phenytoin, valproate)
- Chronic alcoholics who consume > 48 g of alcohol/day for at least one year
Show all 9Show fewer
- Pregnant women
- Subjects not willing to participate
- Known patients with malabsorption or drug abuse
Trial locations and contacts
2 sites in 1 country.
India2 sites
All India Institute of Medical Sciences
New Delhi, National Capital Territory of Delhi, 110029
All India Institute of Medical Sciences
New Delhi, New Delhi, 110029
About this study
Official title: Measurement of Drug Levels and Their Correlation With Hepatotoxicity During Antituberculosis Treatment
The purpose of this study is to evaluate plasma levels of hepatotoxic anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide plus significant metabolites) among patients on antituberculosis treatment (ATT) and compare the same among those who develop drug induced hepatitis on follow up versus those who do not.
Read the detailed description
Tuberculosis (TB) is a major health problem in both the developing and developed countries because of its resurgence in the immunosuppressed patients. World Health Organization (WHO) in 1993 declared tuberculosis to be a 'global emergency' with more than a third of the world's population infected. Globally 8.9 million new cases of tuberculosis occur annually, of which 1.8 million (20%) occur in India.
Short-course chemotherapy containing isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) has proved to be highly effective in the treatment of tuberculosis. One of its adverse effects is hepatotoxicity. It is the most common side effect leading to interruption of therapy. It is associated with mortality of 6-12% if these drugs are continued even after the onset of symptoms. Risk of hepatotoxicity is increased when these drugs are combined.
The time interval between the start of anti-TB drugs and appearance of hepatotoxicity varies from 3 to 135 days. In most cases hepatitis is evident within three months of start of antituberculosis treatment (ATT).
The pathogenesis of drug-induced hepatotoxicity (DIH) is still not entirely clear for most anti TB drugs including rifampicin. Hypersensitivity is a definite possibility Rifampicin induced hepatitis has been postulated to occur as a part of systemic allergic reaction and, due to unconjugated hyperbilirubinaemia as a result of competition with bilirubin for uptake at hepatocyte plasma membrane. DIH caused by rifampicin occurs earlier as compared to isoniazid. While a dose related toxicity may exist, a direct correlation between serum drug levels and hepatotoxicity has not been well reported. Thus the clinical relevance of therapeutic monitoring of serum rifampicin concentrations in managing DIH is still being explored.
Present study done to observe serum rifampicin, isoniazid, pyrazinamide level in patients on ATT and to compare it retrospectively between patients who develop drug induced hepatitis vs those who do not.
- Conditions
- Hepatitis, Tuberculosis
- Keywords
- Plasma levels isoniazid rifampicin pyrazinamide
- Medical subject headings
- Hepatitis, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 2 | Cases - those patients who develop DIH while on regular treatment with anti-TB drugs. Controls - patients who do not develop DIH while on regular treatment with anti-TB drugs. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of plasma levels of isoniazid, rifampicin, pyrazinamide among cases and controls
Measured: 20 months
Secondary outcomes (1)
Evaluation of plasma levels of any significant metabolites among cases and controls
Measured: 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2009 (estimated)
- Study startNov 2007
- Primary completionApr 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HepatitisStudies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences
- Sponsor type
- University, hospital or other
- Investigators
- Surendra K Sharma, MD,Ph.D, Principal investigator, All India Institute of Medical Sciences, New Delhi-110029, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00929786
- Sponsor's protocol ID
- SKS/DIH/01
- Other IDs
- sksharma@aiims.ac.in
- Status last verified
- Nov 2009
- First submitted
- 29 Jun 2009
- Last updated
- 10 Nov 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measurement of Drug Levels and Their Correlation With Hepatotoxicity During Antituberculosis Treatment
- ClinicalTrials.gov ID
- NCT00929786
- Acronym / sponsor ID
- SKS/DIH/01
- Conditions
- Hepatitis, Tuberculosis
- Keywords
- Plasma levels isoniazid rifampicin pyrazinamide
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- All India Institute of Medical SciencesUniversity, hospital or other
- Study start
- Nov 2007
- Primary completion
- Apr 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 30 Jun 2009 (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.
The purpose of this study is to evaluate plasma levels of hepatotoxic anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide plus significant metabolites) among patients on antituberculosis treatment (ATT) and compare the same among those who develop drug induced hepatitis on follow up versus those who do not.
Detailed description
Tuberculosis (TB) is a major health problem in both the developing and developed countries because of its resurgence in the immunosuppressed patients. World Health Organization (WHO) in 1993 declared tuberculosis to be a 'global emergency' with more than a third of the world's population infected. Globally 8.9 million new cases of tuberculosis occur annually, of which 1.8 million (20%) occur in India.
Short-course chemotherapy containing isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) has proved to be highly effective in the treatment of tuberculosis. One of its adverse effects is hepatotoxicity. It is the most common side effect leading to interruption of therapy. It is associated with mortality of 6-12% if these drugs are continued even after the onset of symptoms. Risk of hepatotoxicity is increased when these drugs are combined.
The time interval between the start of anti-TB drugs and appearance of hepatotoxicity varies from 3 to 135 days. In most cases hepatitis is evident within three months of start of antituberculosis treatment (ATT).
The pathogenesis of drug-induced hepatotoxicity (DIH) is still not entirely clear for most anti TB drugs including rifampicin. Hypersensitivity is a definite possibility Rifampicin induced hepatitis has been postulated to occur as a part of systemic allergic reaction and, due to unconjugated hyperbilirubinaemia as a result of competition with bilirubin for uptake at hepatocyte plasma membrane. DIH caused by rifampicin occurs earlier as compared to isoniazid. While a dose related toxicity may exist, a direct correlation between serum drug levels and hepatotoxicity has not been well reported. Thus the clinical relevance of therapeutic monitoring of serum rifampicin concentrations in managing DIH is still being explored.
Present study done to observe serum rifampicin, isoniazid, pyrazinamide level in patients on ATT and to compare it retrospectively between patients who develop drug induced hepatitis vs those who do not.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 2 | – | –Cases - those patients who develop DIH while on regular treatment with anti-TB drugs. Controls - patients who do not develop DIH while on regular treatment with anti-TB drugs. |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Subjects: Patients with diagnosis of CatI/CatIII Tuberculosis attending the out-patient department of the All India Institute of Medical Sciences, New Delhi, will form the study population. Cases - those patients who develop DIH while on regular treatment with anti-TB drugs Controls - age, sex matched patients who do not develop DIH while on regular treatment with anti-TB drugs
Key inclusion criteria (3 listed)
- Patients diagnosed to be suffering from CatI/CatIII tuberculosis by a physician
- Age: 16-65 years
- Patient having normal baseline Liver function (AST/ALT1 < 50/50, serum bilirubin < 1.5 mg/dl)
Key exclusion criteria (9 listed)
- Patients receiving any other drug known to be metabolized by liver by cytochrome P450 3A4 or P-glycoprotein
- Patients diagnosed to have acute viral hepatitis A, B, C, or E or carrier for HBV \& HCV
- Known HIV positive patients
- Presence of chronic liver disease or renal insufficiency
- Concomitant administration of other potential hepatotoxic drugs (methotrexate, phenytoin, valproate)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Evaluation of plasma levels of isoniazid, rifampicin, pyrazinamide among cases and controls
Time frame: 20 months
1 secondary outcome
Evaluation of plasma levels of any significant metabolites among cases and controls
Time frame: 20 months
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 10 Nov 2009.
Related trials for Hepatitis
RecruitingObservational study
Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis
Hepatitis D
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Not yet recruitingObservational study
Elimination of Hepatitis C Virus Among Users of Substances
Hepatitis C in Substance Users
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.
Surendra K Sharma, MD,Ph.D principal investigator
All India Institute of Medical Sciences, New Delhi-110029, India
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis and Tuberculosis, run by All India Institute of Medical Sciences at 2 sites 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 3 inclusion and 9 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 10 Nov 2009. 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 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?
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?
Evaluation of plasma levels of isoniazid, rifampicin, pyrazinamide among cases and controls (time frame: 20 months). 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 10 Nov 2009.