Refining MDR-TB Treatment (T) Regimens (R) for Ultra(U) Short(S) Therapy(T)-PLUS

  • STATUS
    Recruiting
  • End date
    Feb 28, 2023
  • participants needed
    200
  • sponsor
    Huashan Hospital
Updated on 29 January 2021

Summary

The purpose of this study is to assess the efficacy, safety and tolerability of a combination of bedaquiline, linezolid, cycloserine, clofazimine and pyrazinamide treatments guided by PZA sensitivity for 24 to 36 weeks in subjects with fluoroquinolone-resistant MDR-TB .

Description

The TB-TRUST-plus is a phaseIII, multicenter, open-label trial. The purpose of this study is to assess the feasibility of the ultra-short treatment regimen guided by PZA sensitivity among fluoroquinolone-resistant MDR-TB patients.A total of 200 participants with MDR-TB will be recruited and followed up until 84 weeks after the treatment initiation.

This regimen consists of two periods of 24-36 weeks. During the first 4-8 weeks(waiting for pyrazinamide drug sensitivity test), the regimen consists of bedaquiline, linezolid, cycloserine, clofazimine and pyrazinamide. Then based on molecular PZA drug sensitivity results, patients will be in divided into 3 sub-groups: pyrazinamide-susceptible (PZA-S) patients , pyrazinamide-resistant (PZA-R) patients and pyrazinamide-unavailable (PZA-U)patients.

The Regimen for PZA-S patients, consisting of bedaquiline, linezolid, cycloserine and pyrazinamide, are given until the 24th week (prolonged to 28 or 32 weeks if no smear conversion by end of 16th and 20th week).

PZA-R sub-group regimen, consisting of bedaquiline, linezolid, cycloserine and clofazimine ,are given until 36th week (prolonged to 40 or 44 weeks if no smear conversion by end of 16th and 20th week) .

PZA-U sub-group continue the previous regimen, consisting of bedaquiline, linezolid, cycloserine , clofazimine and pyrazinamide ,until 36th week (prolonged to 40 or 44 weeks if no smear conversion by end of 16th and 20th week) .

The primary objective is to access the treatment success rate without relapse of the PZA sensitivity guided ultra short regimen.

The secondary objective is to access the median time to sputum culture conversion. Safety evaluations performed are the routine lab tests, blood glucose, vital signs, electrocardiograph (ECG), reporting of adverse events, peripheral neuropathy brief examining with the use of a Brief Peripheral Neuropathy rating scale(BPNS) and ophthalmologic examination, including assessment of visual acuity and color visionphysical examinations and chest CT. Adverse events will be monitored and promptly managed during the whole treatment course.

Details
Condition drug-resistant tuberculosis
Treatment pyrazinamide, bedaquiline, linezolid, Clofazimine, Cycloserine
Clinical Study IdentifierNCT04717908
SponsorHuashan Hospital
Last Modified on29 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Willing to participate in trial treatment and follow-up and can give informed consent
-70 years old
Has smear-positive pulmonary tuberculosis with initial laboratory results with resistance to rifampicin and isoniazide confirmed by GeneXpert
documented resistance to fluoroquinolones at screening
Can use bedaquiline, linezolid, cycloserine, clofazimine and pyrazinamide drugs concerning the availability and costs of essential medicines
Willing to carry out HIV testing
If the patient is a non-menopausal woman, agree to use or have used effective contraception during treatment
Have an identifiable address and stay in the area during the study period
Willing to follow the follow-up study procedure after the follow-up

Exclusion Criteria

Combined extrapulmonary tuberculosis
HIV antibody positive and AIDS patients
Critically ill patients, and according to the judgment of the research physician, it is impossible to survive for more than 16 weeks
Known to be pregnant or breastfeeding
Unable to attend or follow treatment or follow-up time
Can not take oral medications
Patients with impaired liver function (hepatic encephalopathy, ascites; total bilirubin is more than 2 times higher than the upper limit of normal; ALT or AST is more than 5 times the upper limit of normal)
Blood muscle spasm is more than 1.5 times the upper limit of normal
The investigator believes that there are any social or medical conditions that expose the subject to a safety hazard
Simultaneously apply the drugs (glucocorticoids, interferons) that affect the efficacy of this study; and apply the following drugs contraindicated with the study drug, including non-steroidal anti-inflammatory drugs, monoamine oxidase inhibitors (phenethyl hydrazine, different Carbofurs et al), direct or indirect sympathomimetic drugs (such as pseudoephedrine), vasopressor drugs (such as adrenaline, norepinephrine), dopamine drugs (such as dopamine, dobutamine), 5 a serotonin reuptake inhibitor, a tricyclic antidepressant, a serotonin 5-HTI receptor antagonist (amitriptyline), meperidine or buspirone
Being allergic or intolerant of any study drug
Currently participating in another drug clinical trial
QTc interval 500 milliseconds during screening
Hemoglobin is less than 90g/L or platelet is less than 7510^9/L
Have epilepsy, severe depression, irritability or psychosis
Alcohol abusedrinking more than 64g of ethanol a day for male, 42g for female
Subjects receive more than 2 weeks of bedaquiline, linezolid, cycloserine, clofazimine or pyrazinamide 3 months prior to enrolment
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