NCT05534750

Brief Summary

The objective of this work is to measure the early bactericidal activity of tedizolid, to compare it with the bactericidal activity of linezolid (reference molecule for the treatment of multidrug-resistant tuberculosis) and with that of standard quadruple therapy (reference treatment of drug susceptible tuberculosis).

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
60

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Apr 2023

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 22, 2022

Completed
2 months until next milestone

First Posted

Study publicly available on registry

September 9, 2022

Completed
7 months until next milestone

Study Start

First participant enrolled

April 20, 2023

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2026

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2026

Completed
Last Updated

February 3, 2025

Status Verified

January 1, 2025

Enrollment Period

3 years

First QC Date

July 22, 2022

Last Update Submit

January 31, 2025

Conditions

Keywords

TuberculosisMultidrug ResistantLinezolidTedizolidPyrazinamideRifampicinIsionazidEthambutolEarly Bactericidal Activity

Outcome Measures

Primary Outcomes (1)

  • Assessment of the early bactericidal activity (EBA) of tedizolid (200mg / day) at the end of the first 2 days of treatment (D3).

    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.

    Day 3

Secondary Outcomes (15)

  • Evaluation of the early bactericidal activity (EBA) of tedizolid between Day 3 and Day 8

    Day 8

  • Comparison of the early bactericidal activity (EBA) of tedizolid between Day 1 and Day 3

    Day 3

  • Comparison of the early bactericidal activity (EBA) of tedizolid between Day 3 and Day 8

    Day 8

  • Comparison of the early bactericidal activity of tedizolid 200 mg / day to that of standard quadruple therapy between Day 1 and Day 3

    Day 3

  • Comparison of the early bactericidal activity of tedizolid 200 mg / day to that of standard quadruple therapy between Day 3 and Day 8

    Day 8

  • +10 more secondary outcomes

Study Arms (3)

Tedizolid arm

EXPERIMENTAL

Patients will be taken 1 tablet per day of 200 mg film-coated of Tedizolid (SIVEXTRO®), in the morning for 7 days. Then, the early bactericidal activity will be measured and compared to the other arms.

Drug: Tedizolid arm (SIVEXTRO®)

Linezolid arm

EXPERIMENTAL

Patients will be taken 2 tablets per day of 600 mg film-coated of Linezolid (ZYVOXID®) in the morning for 7 days. Then, the early bactericidal activity will be measured and compared to the other arms.

Drug: Linezolid arm (ZYVOXID®)

Standard quadruple therapy arm

ACTIVE COMPARATOR

Patients will be taken : ISONIAZIDE : o A dosage of 3 to 5mg / kg / day for 7 days (to be taken in the morning on an empty stomach) of Isoniazid (RIMIFON®) RIFAMPICINE : o A dosage of 10mg / kg / day for 7 days (to be taken in the morning on an empty stomach) ETHAMBUTOL : o A dosage of 15-20mg / kg / day for 7 days (to be taken in the morning on an empty stomach) of Ethambutol PYRAZAMIDE : o A dosage of 20-25mg / kg / day for 7 days (to be taken in the morning on an empty stomach) of Pyrazinamide Then, the early bactericidal activity will be measured and compared to the other arms.

Drug: Standard quadruple therapy arm

Interventions

Patients will be taken 1 tablet per day of 200 mg film-coated of Tedizolid (SIVEXTRO®), in the morning for 7 days. Then, the early bactericidal activity will be measured and compared to the other arms.

Tedizolid arm

Patients will be taken 2 tablets per day of 600 mg film-coated of Linezolid (ZYVOXID®) in the morning for 7 days. Then, the early bactericidal activity will be measured and compared to the other arms.

Linezolid arm

Patients will be taken : ISONIAZIDE : o A dosage of 5mg / kg / day for 7 days (to be taken in the morning on an empty stomach) of Isoniazid (RIMIFON®) RIFAMPICINE : o A dosage of 10mg / kg / day for 7 days (to be taken in the morning on an empty stomach) ETHAMBUTOL : o A dosage of 15-20mg / kg / day for 7 days (to be taken in the morning on an empty stomach) of Ethambutol PYRAZAMIDE : o A dosage of 20-25mg / kg / day for 7 days (to be taken in the morning on an empty stomach) of Pyrazinamide Then, the early bactericidal activity will be measured and compared to the other arms.

Standard quadruple therapy arm

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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);
  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Bacteriology department- Hôpital Saint-Antoine

Paris, 75012, France

RECRUITING

MeSH Terms

Conditions

TuberculosisTuberculosis, Multidrug-Resistant

Interventions

tedizolid phosphate

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Study Officials

  • Nicolas VEZIRIS, PU-PH

    Assistance Publique - Hôpitaux de Paris

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicolas VEZIRIS, PU-PH

CONTACT

Ruxandra CALIN, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 22, 2022

First Posted

September 9, 2022

Study Start

April 20, 2023

Primary Completion

April 1, 2026

Study Completion

May 1, 2026

Last Updated

February 3, 2025

Record last verified: 2025-01

Locations