pulmonary tuberculosis MedDRA version: 12.1 Level: LLT Classification code 10037440 Term: Pulmonary tuberculosis
Conditions
Interventions
Product Name: isoniazid
Product Code: INH
Pharmaceutical Form: Capsule*
INN or Proposed INN: isoniazid
CAS Number: 54-85-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration n
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -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 radiological evidence of a pulmonary infiltrate. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -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 -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 abuse -Patients with known / continuous severe alcohol abuse (drinking more than 60 g and less than 200 g alcohol daily) presenting with relevant (more than 20%) abnormalities of the following liver tests: ALT and/or AST and/or AP and/or bilirubin -Patients with known / continuous very severe alcohol abuse (drinking equal to or more than 200 g alcohol daily) irrespective of the results of the following liver tests: ALT and/or AST and/or AP and/or bilirubin -Patients who participate in other interventional clinical studies -Female patients who are pregnant or lactating -For women of child-bearing potential only: refusal to use of a reliable contraception during the whole study -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 Exclusion criteria after allocation. -Infection with Mycobacterium avium complex -Resistance of M. tuberculosis to isoniazid at the first screening test (initial culture).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study is conducted to compare safety and efficacy of isoniazid administered as an adjusted dose based on NAT2 genotype and as a standard dose ;Secondary Objective: -Population pharmacokinetics/pharmacodynamics of isoniazid and (optional) other antituberculosis drugs -(optional) To obtain data on other factors and their relationship to treatment success and/or NAT2, including early bactericidal activity (EBA), specification of Mycobacterium tuberculosis (M. tuberculosis) strains, pharmacogenetics of the first-line antituberculosis drugs other than isoniazid, utility of the interferon-gamma (IFN-gamma) test -(optional) Cost-effectiveness analysis of NAT2-based isoniazid dose adjustment ;Primary end point(s): -Incidence of hepatotoxicity in Test and Control groups occurring up to week 8 of therapy, defined according to the following criteria:- in patients with normal results of liver tests before treatment: increase to more than 2-fold above upper limit of normal range in ALT or conjugated bilirubin or combined increase in AST, AP and total bilirubin provided one of them is more than 2-fold;- in patients with abnormal results of liver tests before treatment: increase to more than 2-fold above the levels before administration (baseline) in ALT or conjugated bilirubin or combined increase in AST, AP and total bilirubin provided one of them is more than 2-fold. -Incidence of early treatment failure assessed in patients included with a positive sputum smear on the basis of bacteriological examinations (sputum microscopy and culture) and defined as continuous or recurrently positive sputum cultures up to 8 weeks of therapy, or, in patients without a positive sputum smear upon inclusion/producing no sputum, assessed on the basis of clinical evaluation indicating lack of response to the given treatment | — |
Countries
Bulgaria, Germany
Outcome results
None listed