TEDIZOLID PHOSPHATE for Pulmonary tuberculosis

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years old and <75 years old"}
• {"criterion_text":"- Woman on childbearing age should be on effective contraception during the duration of the study and up to 6 months after treatment; a mechanical contraception (use of condom) will be strongly recommended"}
• {"criterion_text":"- Male (effective contraception must be used during duration of the study and up to 3 months after treatment)"}
• {"criterion_text":"- Patient with a first infection with Mycobacterium tuberculosis of pulmonary localization suspected by the presence of a clinical pulmonary symptomatology, a chest X-ray or an abnormal chest computed tomography, and the positive microscopic examination of a sputum (AFB +, presence of AFB) with confirmation of tuberculosis by a genotypic test demonstrating no resistance to rifampicin, without clinical signs of extra-thoracic involvement"}
• {"criterion_text":"- State medical assistance application being processed ( If patient does not benefit from social security),"}
• {"criterion_text":"- Signature of informed consent"}

Exclusion criteria

• {"criterion_text":"- Resistance to one of the anti-tuberculosis drugs used detected by a genotypic test in accordance with the recommendations of the High Council of Public Health of 2015;"}
• {"criterion_text":"- Protected adults (under guardianship, curatorship) and under safeguard of justice"}
• {"criterion_text":"- Significant laboratory abnormalities (hemoglobin <9g / dl, polynuclear neutrophils <500 / mm3, platelets <50,000 / mm3, creatinine clearance <30ml / min, ASAT or ALAT> 3N, and total bilirubin> 3N)"}
• {"criterion_text":"- Hyperuricaemia"}
• {"criterion_text":"- Porphyria"}
• {"criterion_text":"- Optic neuritis or peripheral neuropathy"}
• {"criterion_text":"- BMI≤ 16 kg/m2"}
• {"criterion_text":"- Participation in other interventional research"}
• {"criterion_text":"- Current treatment with one or more medications contraindicated in combination with linezolid: Linezolid should not be used in patients treated with monoamine oxidase A or B inhibitors (for example: phenelzine, isocarboxacid, selegiline, moclobemide) or who received one of these products in the previous two weeks"}
• {"criterion_text":"- Combination with bictegravir, cobicistat, daclatasvir, dasabuvir, delamanid, grazoprevir/elbasvir, protease inhibitors boosted by ritonavir, isavuconazole, ledipasvir, lurasidone, midostaurin, ombitasvir/paritaprevir, praziquantel, rilpivirine, sofosbuvir, velpatasvir, voriconazole, voxilaprevir Gastrointestinal topicals, antacids and adsorbents and salts and aluminum hydroxides"}
• {"criterion_text":"- History of anti-tuberculosis treatment;"}
• {"criterion_text":"- History of treatment in the previous two years with one of the antibiotics evaluated in this trial lasting more than one month;"}
• {"criterion_text":"- Absolute contraindication to the use of at least one of the test molecules (isoniazid, rifampicin, ethambutol, pyrazinamide, linezolid, tedizolid);"}
• {"criterion_text":"- Tuberculosis having, in the opinion of the investigator, severity criteria not allowing to wait 7 days before starting standard treatment (oxygenorequirement, severe immunosuppression, extra-pulmonary involvement, any sign of severity requiring treatment in intensive care unit);"}
• {"criterion_text":"- HIV-infected patient receiving protease inhibitors whose antiviral treatment cannot be changed and therefore cannot receive rifampicin; or any other drug contraindicated with one of the study treatments (the list of contraindicated drugs is detailed in the following non-inclusion criteria)."}
• {"criterion_text":"- Neoplastic pathology during treatment with chemo and / or radiotherapy;"}
• {"criterion_text":"- Decompensated cirrhosis;"}
• {"criterion_text":"- Pregnancy, desire to become pregnant, breast-feeding (for women of childbearing potential, contraception should be used for the duration of the study and up to 6 months after treatment, mechanical contraception will be strongly recommended and up to 3 months after treatment);"}

Primary endpoints

• {"endpoint_text":"- The measurement will be done as follow: EABD1D3= (log10 number of CFU (CFU= colony forming unit) of M. tuberculosis on medium 7H11/mL of sputum on D1) - (log10number of CFU of M. tuberculosis on medium 7H11/mL of sputum on D3)/2.","definition_or_measurement_approach":"EABD1D3= (log10 number of CFU of M. tuberculosis on medium 7H11/mL of sputum on D1) - (log10 number of CFU of M. tuberculosis on medium 7H11/mL of sputum on D3)/2 (i.e. early bactericidal activity of tedizolid at end of first 2 days (D3))."}

Secondary endpoints

• {"endpoint_text":"- The measurement will be done as follow: EBAD3D8= (log10 number of CFU (CFU=colony forming unit) of M. tuberculosis on medium 7H11/mL of sputum on D3) - ( log10 number of CFU of M. tuberculosis on medium 7H11/mL of sputum at D8)/5","definition_or_measurement_approach":"EBAD3D8 = (log10 CFU on 7H11/mL of sputum at D3) - (log10 CFU on 7H11/mL of sputum at D8) / 5 (early bactericidal activity between D3 and D8)."}
• {"endpoint_text":"- Compare the early bactericidal activity of tedizolid 200 mg / day to that of linezolid 1200 mg / day between Day 1 and Day 3 and between Day 3 and Day 8","definition_or_measurement_approach":"Comparison of EBA metrics (ABPJ1J3 and ABPJ3J8) between tedizolid (200 mg/day) and linezolid (1200 mg/day) measured by changes in log10 CFU over specified intervals."}
• {"endpoint_text":"- Compare the early bactericidal activity of tedizolid 200 mg / day to that of standard quadruple therapy between Day 1 and Day 3 and between Day 3 and Day 8","definition_or_measurement_approach":"Comparison of EBA metrics (ABPJ1J3 and ABPJ3J8) between tedizolid (200 mg/day) and standard quadruple therapy measured by changes in log10 CFU over specified intervals."}
• {"endpoint_text":"- ABPJ1J3 of tedizolide measured in terms of time to positivity of cultures in liquid medium called ABPJ1J3L= (time to positivity of culture of sample at D3) - (time to positivity of culture of sample at D1)/2 (i.e. after the first 2 days of treatment with tedizolide)","definition_or_measurement_approach":"ABPJ1J3L = (time to positivity of liquid culture at D3) - (time to positivity at D1) / 2; measures bactericidal activity by change in time-to-positivity."}
• {"endpoint_text":"- Bactericidal activity in liquid medium between D3 and D8 (ABPJ3J8L) of tédizolide","definition_or_measurement_approach":"ABPJ3J8L measured as change in time-to-positivity of liquid cultures between D3 and D8."}
• {"endpoint_text":"- ABPJ1J3L and ABPJ3J8L of tedizolide compared with linezolide","definition_or_measurement_approach":"Comparative analysis of liquid-medium bactericidal activity (time-to-positivity derived metrics) between tedizolid and linezolid."}
• {"endpoint_text":"- ABPJ1J3L and ABPJ3J8L of tedizolide compared with standard four-therapy treatment","definition_or_measurement_approach":"Comparative analysis of liquid-medium bactericidal activity (time-to-positivity derived metrics) between tedizolid and standard quadruple therapy."}
• {"endpoint_text":"- Total and free concentration of tedizolid measured at 0, 1, 3, 5, and 24h, Area under the curve (AUC)","definition_or_measurement_approach":"Pharmacokinetic measurements: total and free tedizolid concentrations at specified timepoints; calculation of AUC."}
• {"endpoint_text":"- Toxicity of tedizolide assessed at D7 and D30. Adverse events leading to premature discontinuation of treatment","definition_or_measurement_approach":"Safety endpoints: adverse events assessment at D7 and D30 and recording of events leading to treatment discontinuation."}

France

Earliest CTIS Part Ii Submission Date

25-07-2024

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

593

Number Of Sites

7

Number Of Participants

60

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France