Pulmonary TuberculosisPhase 3NCT00571753
Isoniazid Dose Adjustment According to NAT2 Genotype (IDANAT2)
A Phase 3 study testing isoniazid in people with Pulmonary Tuberculosis, run by University of Cologne at 12 sites in 3 countries.
Trial summary
The study is conducted to compare safety and efficacy of isoniazid administered as an adjusted dose based on NAT2 (arylamine N-acetyltransferase type 2)genotype and as a standard dose. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Tuberculosis
- What is being tested?
- isoniazid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 900 participants
- Where
- 12 sitesin 3 countries
- Study dates
- Jun 2008to Feb 2012
- Phase
- Phase 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent
- Patient is willing and able to comply with all trial requirements, inclusive genotyping procedure
- Patient is between 18 and 75 years of age (inclusive) during the whole trial, male or female
- Patient has newly diagnosed pulmonary tuberculosis for whom daily antituberculosis therapy is indicated
- Patient has a smear-positive sputum
- Patient has radiological evidence of a pulmonary infiltrate.
Who cannot join
- Patients with known contraindications for isoniazid: acute hepatitis, macroscopic hematuria, allergy to isoniazid, peripheral neuritis, coagulopathy, severe haemorrhagic diathesis, seizure disorders, psychosis
- Patients with advanced or unstable chronic liver disease which is confirmed on results of biochemical or serological tests by eligibility assessment (relevant abnormalities of the following liver tests: ALT, AST, AP, total and conjugated bilirubin; positive serology for hepatitis), if the assessed risk-benefit ratio for the participation in the study is unfavourable (inclusion upon a decision of clinical investigator)
- Patients with a severe, life-threatening disease with a life expectancy of less than 2 years
- Patients known to have AIDS (CD4+ count <200/ml) or HIV-seropositive patients who are receiving HAART (highly active antiretroviral therapy). Note: HIV-positive patients may be included
- Patients with diabetes mellitus
- Patients with renal insufficiency (creatinine clearance < 30mL / min / 1.73m2) and patients on hemodialysis
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- Patients with any other clinical conditions suggesting that he/she should not be included (decision of the clinical investigator)
- Patients with chronic infections requiring concomitant systemic antibacterial agents that are also active against M. tuberculosis (i.e. fluoroquinolones, aminoglycosides, macrolides)
- Patients with intake of systemic antibacterial agents that are also active against M. tuberculosis (i.e. fluoroquinolones, aminoglycosides, macrolides) within 4 weeks prior to antituberculosis treatment
- Patients who have ever received antituberculosis chemotherapy
- Patients who take any hepatotoxic agent on regular basis or have taken it within 3 month before study onset
- Patients with known drug / continuous severe alcohol abuse (drinking more than 60 g alcohol daily)
- Patients who participate in other interventional clinical studies;
- Female patients who are pregnant or lactating;
- Female patients not willing and capable to use two different contraceptive methods throughout the study, e.g. double barrier methods (e.g. diaphragm and condom by the partner, intrauterine devise and condom, sponge and condom, spermicide and condom). Acceptable alternatives of effective contraception are also sexual abstinence or vasectomized partner. In contrast, oral contraceptives are not recommended, since the effectiveness of them may be reduced due to a possible interaction with rifampicin
- Patients who are placed in a closed institution as a result of a court or any other authorities' decision
- Patients who are known or suspected not to comply with the study directives and/or known or suspected not to be reliable or trustworthy
- Patients who are known or suspected not to be capable of understanding and evaluating the information that is given to them as part of the formal information policy (informed consent), in particular regarding the foreseeable risks to which they will be exposed.
- Patients with any of followings will not be included into evaluation for efficacy:
- Infection with Mycobacterium avium complex
- Resistance of M. tuberculosis to isoniazid at the first screening test (initial culture).
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
Germany9 sites
Zentralkrankenhaus Bad Berka GmbH
Bad Berka, 99437
Karl-Hansen-Klinik
Bad Lippspringe, 33175
Helios Klinikum Emil von Behring GmbH
Berlin, 14165
Department I of Internal Medicine, University Hospital, University of Cologne
Cologne, 50931
Medizinische Klinik I, Abteilung Pneumologie/Allergologie, Universitätsklinikum Frankfurt am Main
Frankfurt am Main, 60590
Abteilung Innere Medizin/ Pneumologie, Thoraxklinik am Universitätsklinikum Heidelberg
Heidelberg, 69126
Lungenfachklinik Immenhausen
Immenhausen, 34376
Diakoniekrankenhaus Rotenburg
Rotenburg (Wümme), 27356
Division of Infectious Diseases and Clinical Immunology, Department of Internal Medicine
Ulm, 89081
Poland2 sites
Specialized Hospital of Lung Diseases and Tuberculosis in Wielkopolska in Chodzież
Chodzież, 64-800
Department of Pulmonal Diseases, K. Marcinkowski University of Medical Sciences
Poznan, 60-569
Bulgaria1 site
Specialized Hospital for Active Treatment of Pulmonary Diseases "Sveta Sofia"
Sofia, 1431
About this study
Official title: A Double-blind, Multicentre, Parallel Group, Randomised, Controlled Trial to Evaluate the Possible Benefit of Isoniazid Dose Adjustment According to the Genotype for NAT2 (Arylamine N-acetyltransferase Type 2) in Patients With Pulmonary Tuberculosis
The study is conducted to compare safety and efficacy of isoniazid administered as an adjusted dose based on NAT2 (arylamine N-acetyltransferase type 2)genotype and as a standard dose.
The hypothesis is that the genotype-adjusted dose is superior to the standard dose with regard to hepatotoxicity and early treatment failure, respectively, in the group of slow and rapid acetylators of NAT2.
- Conditions
- Pulmonary Tuberculosis
- Being tested
- isoniazid
- Keywords
- pulmonary tuberculosis, NAT2 genotyping, hepatotoxicity of isoniazid
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
isoniazidDrug
modified daily isoniazid dose according to NAT2 genotype (appr. 2.5 mg/kg, 5 mg/kg and 7.5 mg/kg for slow, intermediate and rapid acetylators, respectively).
isoniazidDrug
Treatment with a standard isoniazid dose of isoniazid (appr. 5 mg/kg b.w.)
| Study group | Role | What they receive |
|---|---|---|
| Test | Experimental | Isoniazid dose adapted according to NAT2 status i.e. appr. 2.5 mg/kg, 5 mg/kg and 7.5 mg/kg for slow, intermediate and rapid acetylators, respectively Receives: Drug: isoniazid |
| Control | Active comparator | Treatment with standard isoniazid dose (appr. 5 mg/kg b.w.) Receives: Drug: isoniazid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of early treatment failure, defined as continuous or recurrently positive sputum cultures
Measured: occurring up to week 8 of therapy
Secondary outcomes (3)
Further adverse events of isoniazid
Measured: up to week 8 of therapy
Time course of sputum conversion
Measured: up to week 8 of therapy
Duration of hospitalization
Measured: up to week 8 of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2007 (estimated)
- Study startJun 2008
- Primary completionDec 2011 (estimated)
- Study completionFeb 2012 (estimated)
Why it stopped: Enrolling participants has halted prematurely due to a low recruitment rate.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary TuberculosisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 900 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cologne
- Sponsor type
- University, hospital or other
- Investigators
- Gerd Fätkenheuer, Prof. Dr. med., Principal investigator, Department I of Internal MedicineUniversity Hospital, University of Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00571753
- Sponsor's protocol ID
- IDANAT2
- Other IDs
- EUDRACT Number:2007-000224-41
- Status last verified
- Feb 2011
- First submitted
- 11 Dec 2007
- Last updated
- 28 Feb 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Multicentre, Parallel Group, Randomised, Controlled Trial to Evaluate the Possible Benefit of Isoniazid Dose Adjustment According to the Genotype for NAT2 (Arylamine N-acetyltransferase Type 2) in Patients With Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT00571753
- Acronym / sponsor ID
- IDANAT2
- Conditions
- Pulmonary Tuberculosis
- Keywords
- pulmonary tuberculosis, NAT2 genotyping, hepatotoxicity of isoniazid
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrolling participants has halted prematurely due to a low recruitment rate.
- Enrolment
- 900 participants (estimated)
- Lead sponsor
- University of CologneUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Dec 2011 (estimated)
- Study completion
- Feb 2012 (estimated)
- First posted
- 12 Dec 2007 (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 study is conducted to compare safety and efficacy of isoniazid administered as an adjusted dose based on NAT2 (arylamine N-acetyltransferase type 2)genotype and as a standard dose.
The hypothesis is that the genotype-adjusted dose is superior to the standard dose with regard to hepatotoxicity and early treatment failure, respectively, in the group of slow and rapid acetylators of NAT2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test | Experimental | Drug: isoniazidIsoniazid dose adapted according to NAT2 status i.e. appr. 2.5 mg/kg, 5 mg/kg and 7.5 mg/kg for slow, intermediate and rapid acetylators, respectively |
| Control | Active comparator | Drug: isoniazidTreatment with standard isoniazid dose (appr. 5 mg/kg b.w.) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent
- Patient is willing and able to comply with all trial requirements, inclusive genotyping procedure
- Patient is between 18 and 75 years of age (inclusive) during the whole trial, male or female
- Patient has newly diagnosed pulmonary tuberculosis for whom daily antituberculosis therapy is indicated
- Patient has a smear-positive sputum
Key exclusion criteria (21 listed)
- Patients with known contraindications for isoniazid: acute hepatitis, macroscopic hematuria, allergy to isoniazid, peripheral neuritis, coagulopathy, severe haemorrhagic diathesis, seizure disorders, psychosis
- Patients with advanced or unstable chronic liver disease which is confirmed on results of biochemical or serological tests by eligibility assessment (relevant abnormalities of the following liver tests: ALT, AST, AP, total and conjugated bilirubin; positive serology for hepatitis), if the assessed risk-benefit ratio for the participation in the study is unfavourable (inclusion upon a decision of clinical investigator)
- Patients with a severe, life-threatening disease with a life expectancy of less than 2 years
- Patients known to have AIDS (CD4+ count <200/ml) or HIV-seropositive patients who are receiving HAART (highly active antiretroviral therapy). Note: HIV-positive patients may be included
- Patients with diabetes mellitus
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 |
|---|---|---|
| isoniazidmodified daily isoniazid dose according to NAT2 genotype (appr. 2.5 mg/kg, 5 mg/kg and 7.5 mg/kg for slow, intermediate and rapid acetylators, respectively). | Drug | Test |
| isoniazidTreatment with a standard isoniazid dose of isoniazid (appr. 5 mg/kg b.w.) | Drug | Control |
Primary outcome
Incidence of early treatment failure, defined as continuous or recurrently positive sputum cultures
Time frame: occurring up to week 8 of therapy
3 secondary outcomes
Further adverse events of isoniazid
Time frame: up to week 8 of therapy
Time course of sputum conversion
Time frame: up to week 8 of therapy
Duration of hospitalization
Time frame: up to week 8 of therapy
Results and safety
The study was stopped early (reason given: Enrolling participants has halted prematurely due to a low recruitment rate.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2011.
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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.
Gerd Fätkenheuer, Prof. Dr. med. principal investigator
Department I of Internal MedicineUniversity Hospital, University of Cologne
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing isoniazid in people with Pulmonary Tuberculosis, run by University of Cologne at 12 sites in 3 countries.
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 6 inclusion and 21 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: stopped early, as of the sponsor's last update on 28 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany, Poland, Bulgaria. 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.
What does this phase mean?
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 was stopped early (reason given: Enrolling participants has halted prematurely due to a low recruitment rate.). Results are not available in the source record.
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?
Incidence of early treatment failure, defined as continuous or recurrently positive sputum cultures (time frame: occurring up to week 8 of therapy). 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 28 Feb 2011; AzTrials last refreshed its copy on 6 Nov 2026.