Comparing the effectiveness of tedizolid and linezolid for treating tuberculosis

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

This study is testing if a new drug called tedizolid can work better than an existing drug, linezolid, in helping people with tuberculosis feel better by reducing the bacteria in their lungs.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 1 site (Paris)
• Trial ID: NCT05534750 on ClinicalTrials.gov

What this trial studies

This Phase 2 clinical trial evaluates the early bactericidal activity of tedizolid compared to linezolid and standard quadruple therapy for tuberculosis. It is a multicentric, open-label, randomized controlled trial involving 60 patients divided into three treatment groups. Each group will receive either tedizolid, linezolid, or standard quadruple therapy for a duration of 7 days. The primary goal is to assess the effectiveness of tedizolid in reducing the bacterial load of Mycobacterium tuberculosis in patients with pulmonary tuberculosis.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with a first infection of pulmonary tuberculosis confirmed by positive sputum tests and no resistance to rifampicin.

Not a fit: Patients with known resistance to the treatment drugs or those with extra-thoracic tuberculosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with multidrug-resistant tuberculosis.

How similar studies have performed: Other studies have shown promising results with similar approaches, particularly with linezolid, but the use of tedizolid in this context is relatively novel.

Eligibility criteria

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;
* History of anti-tuberculosis treatment (patients with a documented negative genotypic test for isoniazid and rifampicin resistance may be included)
* 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);
* 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
* Current treatment with one or more medications contraindicated in combination with quadritherapy:
* 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

Where this trial is running

Paris

• Bacteriology department- Hôpital Saint-Antoine — Paris, France (Recruiting)

Study contacts

• Principal investigator: Nicolas VEZIRIS, PU-PH — Assistance Publique - Hôpitaux de Paris
• Study coordinator: Nicolas VEZIRIS, PU-PH

Conditions Tuberculosis; Multidrug Resistant Tuberculosis; Multidrug Resistant; Linezolid; Tedizolid; Pyrazinamide; Rifampicin; Isionazid