Tuberculosis
Conditions
Interventions
High dose rifampicin (35 mg/kg) will be given once daily for 8 weeks. After 8
weeks, participants will be switched to the standard of care as per the local
and national guidelines. Visits, diagnosti
Sponsors
Vall dHebron University Hospital
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: The participant must fulfill either criteria nr. 1-4 AND nr. 5 OR criteria nr. 1-4 AND 6, AND anyone of 7-14: 1. Subjects with confirmed or probable pulmonary or extra pulmonary DS-TB. 2. Informed consent provided. 3. Positive smear, positive Xpert MTB/RIF test, positive M. tuberculosis culture (confirmed cases) OR histological study compatible with necrotizing granulomas OR a liquid biochemistry (pleural, pericardial, ascites or cerebrospinal fluid) suggestive of TB together with clinical symptoms resembling TB disease in the absence of any other possible cause (probable cases). 4. Female participants of childbearing age must have a negative pregnancy test at baseline. AND 5. Age >= 60 years old. OR 6. Age >= 18 years AND one of the following 7. Body mass index = 2 units of alcohol (1 unit of alcohol: 4% alcohol 250ml (ie beer); 4.5% alcohol 218ml (i.e. cider); 13% alcohol 76ml (i.e. wine); 40% alcohol 25ml (i.e. whisky)) 13. Chronic liver disease of any other cause (metabolic, toxic, autoimmune) 14. Central Nervous System TB involvement
Exclusion criteria
Exclusion criteria: Subjects will be excluded from entry if ANY ONE of the criteria listed below is met: 1. Rifampicin resistance confirmation. 2. Barthel index 5x upper limit of normal , Total bilirubin > 5x upper limit of normal, Patients with a Child-Pugh grade C cirrhosis or acute decompensation of their chronic liver disease at enrolment.] 4. Subjects with known allergy or sensitivity to rifampicin, or any of the other components of DS-TB treatment. 5. Treatment with any of the following: rifampicin, isoniazid, pyrazinamide, ethambutol, levofloxacin, or moxifloxacin within the last month for at least 14 days or current TB treatment for more than 7 days. 6. The subject is enrolled in any other investigational trial that includes a drug intervention. 7. Subjects with solid organ transplantation or bone marrow transplantation. 8. Subjects with an active onco-hematological neoplasm. 9. Previous severe pulmonary disease, other than pulmonary DS-TB, according to local investigator. 10. Pre-existing epilepsy or psychiatric disorder according to local investigator. 11. Ischemic heart disease OR severe arrhythmia within 6 months OR Atrial Fibrillation with oral anticoagulant therapy indication when transitioning to low-molecular weight heparin is not feasible. 12. Positive pregnancy test 13. Breastfeeding women. 14. The subject used any drugs or substances known to be strong inhibitors or inducers of cytochrome P450 enzymes which are involved in the degradation pathways of rifampicin within the time windows specified in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary safety endpoint: the proportion of participants with one or more SAE (grade 3 or superior) at the end of the intensive phase (first 8 weeks of treatment). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary safety endpoints: * Proportion of participants with any adverse event (tolerability endpoint). * Proportion of participants needing to stop the study regimen for any reason other than microbiological ineligibility. * Sensitivity analyses of the primary safety endpoint assuming all losses to follow-up and non-tuberculosis deaths have an unfavorable outcome and assuming all losses to follow-up and non-tuberculosis deaths have a favorable outcome. Secondary efficacy endpoints: * Proportion of participants who have sputum culture conversion at 8 weeks after treatment onset or proportion of participants with clinical and radiological improvement (if follow-up images are available for extra-pulmonary TB) but without a follow up sample at 8 weeks after treatment onset. * Proportion of participants who suffer a relapse at 1 year after treatment completion. * Time to sputum culture conversion. * Time to negative sputum smear. * Time to negative smell print test using an eNose device. * Distribution of time to sputum culture positivity. * Distribution of time to sputum smear bacterial load decrease (see the SOP for standard procedures for bacterial counting on a sputum smear). * Correlation of the AUC/MIC values with time to sputum culture conversion, sputum smear conversion, time to sputum culture positivity and sputum smear bacterial load decrease. * Sensitivity analyses will be performed for the secondary efficacy endpoints assuming all losses to follow-up and non-tuberculosis deaths have an unfavorable outcome and assuming all losses to follow-up and non-tuberculosis deaths have a favorable outcome. * Mean difference in SF-12 and St George*s respiratory questionnaire scores at 0 and 8. * Proportion of participants who are classified as having a failure during treatment and relapse after completion of full treatment regimen and first year of follow up. | — |
Countries
Netherlands
Outcome results
None listed