Evaluation of the Early Bactericidal Activity of Tedizolid and Linezolide Against Mycobacterium Tuberculosis (TEDITUB)

Phase 1

• Conditions: first suspected infection with Mycobacterium tuberculosis in the lungs; MedDRA version: 20.0Level: SOCClassification code: 10021881Term: Infections and infestations Class: 1; MedDRA version: 20.1Level: LLTClassification code: 10070578Term: Multidrug resistant tuberculosis Class: 10021881; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: CTIS2024-512759-19-00
• Lead Sponsor: Assistance Publique Hopitaux De Paris

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-19
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Age = 18 years old and <75 years old, 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, Male (effective contraception must be used during duration of the study and up to 3 months after treatment), 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, State medical assistance application being processed ( If patient does not benefit from social security),, Signature of informed consent

Exclusion Criteria

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;, Protected adults (under guardianship, curatorship) and under safeguard of justice, 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), Hyperuricaemia, Porphyria, Optic neuritis or peripheral neuropathy, BMI= 16 kg/m2, Participation in other interventional research, 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, 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, History of anti-tuberculosis treatment;, History of treatment in the previous two years with one of the antibiotics evaluated in this trial lasting more than one month;, Absolute contraindication to the use of at least one of the test molecules (isoniazid, rifampicin, ethambutol, pyrazinamide, linezolid, tedizolid);, 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);, 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)., Neoplastic pathology during treatment with chemo and / or radiotherapy;, Decompensated cirrhosis;, 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);

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Assessment of the early bactericidal activity (EBA) of tedizolid (200mg / day) at the end of the first 2 days of treatment (D3).;Secondary Objective: Evaluation of the early bactericidal activity (EBA) of tedizolid between Day 3 and Day 8, Comparison of the early bactericidal activity (EBA) of tedizolid and linezolide between Day 1 and Day 3 and between Day 3 and Day 8, Comparison of the early bactericidal activity (EBA) of tedizolid and quadruple therapy between Day 1 and Day 3 and between Day 3 and Day 8, Tedizolid pharmacokinetics'measurement, Evaluation of Tedizolid's tolerance;Primary end point(s): 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.