RIFAMPICIN for Tuberculosis (drug-susceptible pulmonary and extrapulmonary)

Inclusion criteria

• {"criterion_text":"-1.\tSubjects with confirmed or probable pulmonary or extra pulmonary DS-TB.\n-2.\tInformed consent provided.\n-3.\tPositive 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).\n-4.\tFemale participants of childbearing age must have a negative pregnancy test at baseline.\n-5.\tAge ≥ 60 years old; or Age ≥ 18 years and any of the followings: Body mass index ≤ 18.5 Human Immunodeficiency Virus (HIV) infection. Diabetes Mellitus Hepatitis C virus (HCV) infection (positive HCV serology) Hepatitis B virus (HBV) infection (positive HBV surface antigen or anti-core antibodies) Daily alcohol intake ≥ 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)) Chronic liver disease of any other cause (metabolic, toxic, autoimmune) Central Nervous System TB involvement"}

Exclusion criteria

• {"criterion_text":"-1.\tRifampicin resistance confirmation.\n-2.\tBarthel index <40 for subjects older than 60 years old.\n-3.\tSigns of significant liver disease: o\tLiver enzymes (AST or ALT) > 5x upper limit of normal o\tTotal bilirubin > 3x upper limit of normal o\t Subjects with a Child-Pugh grade C cirrhosis or acute decompensation of their chronic liver disease at enrolment. o\tAny other grade 3-4 hepatobiliary alteration according to the CTCAE v5.\n-4.\tSubjects with known allergy or sensitivity to rifampicin, or any of the other components of DS-TB treatment.\n-5.\tTreatment 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.\n-6.\tThe subject is enrolled in any other investigational trial that includes a drug intervention.\n-7.\tSubjects with solid organ transplantation or bone marrow transplantation.\n-8.\tSubjects with an active onco-hematological neoplasm requiring chemotherapy or immune therapy.\n-9.\tPrevious severe pulmonary disease, other than pulmonary DS-TB, according to local investigator.\n-10.\tPre-existing epilepsy or psychiatric disorder according to local investigator.\n-11.\tIschemic 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.\n-12.\tPositive pregnancy test\n-13.\tBreastfeeding women.\n-14.\tThe 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 table 2."}

Primary endpoints

• {"endpoint_text":"-proportion of participants with one or more SAE (i.e. grade 3 or 4 AE) at 8 weeks of treatment","definition_or_measurement_approach":"Safety defined as proportion of participants experiencing severe adverse events (grade 3 or superior according to the Common Terminology Criteria for Adverse Events, CTCAE version 5) at 8 weeks of treatment compared to historical controls on 10 mg/kg/day of rifampicin."}

Secondary endpoints

• {"endpoint_text":"-Eficaccy: The proportion of participants with a favorable outcome at 8 weeks of treatment","definition_or_measurement_approach":"Proportion of participants with a favorable outcome at 8 weeks; efficacy assessment includes culture conversion in liquid media at 8 weeks for pulmonary TB subjects (as described in secondary objectives)."}
• {"endpoint_text":"-Tolerability: proportion of participants having one or more AE in the prospective cohort.","definition_or_measurement_approach":"Tolerability defined based on the proportion of all adverse events (grade 1-4) including treatment dropout rates in the prospective cohort."}
• {"endpoint_text":"-efficacy: time to sputum culture conversion from positive to negative","definition_or_measurement_approach":"Time from baseline positive sputum culture to first negative sputum culture (culture conversion) measured in liquid media."}
• {"endpoint_text":"-Correlation of the AUC/MIC values with time to sputum culture conversion adjusted with other explanatory covariates","definition_or_measurement_approach":"Pharmacokinetic/pharmacodynamic analysis correlating rifampicin AUC/MIC values with time to sputum culture conversion, adjusted for covariates."}
• {"endpoint_text":"-changes in quality of life questionnaires and in TB associated costs from all sites will be depicted","definition_or_measurement_approach":"Changes in quality of life questionnaire scores and TB-associated costs will be collected and described across sites."}

Spain

Latest Decision Or Authorization Date

04-02-2025

Number Of Sites

1

Number Of Participants

25

Netherlands

Latest Decision Or Authorization Date

04-02-2025

Number Of Sites

1

Number Of Participants

25

Primary sponsor

Full Name

Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain