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

NCT03867136 | Completed Phase 4 DMC

• 1 other identifier: KY2018-331
• Study Type: interventional
• Target: 354
• Locations: 1 country
• Sites: 13

Brief Summary

The purpose of this study is to assess the efficacy, safety and tolerability of a combination of levofloxacin, linezolid, cycloserine and pyrazinamide (or clofazimine if resistant to pyrazinamide) treatments for 24 to 32 weeks (regimen consisted of clofazimine for 36\~44 weeks) in subjects with multidrug-resistant tuberculosis (MDR-TB) compared to WHO standardized shorter regimen of 36-44 weeks.

Conditions

Multidrug Resistant Tuberculosis

Keywords

Multidrug resistant tuberculosis; shorter treatment; all-oral regimen

Outcome Measures

Primary Outcomes (1)

• Treatment success rate of the ultra short regimen

  To compare the treatment success rate without relapse between the PZA sensitivity guided all oral ultra short regimen group and the WHO standardized shorter regimen group. Treatment outcomes will be classified into favourable outcome and unfavourble outcome.

  84 weeks after randomization.

Secondary Outcomes (2)

• The median time to Sputum Culture Conversion

  12-36 weeks after treatment initiation

• The frequency of grade 3 or greater adverse events among patients treated with the ultra short regimen

  84 weeks after treatment initiation

Study Arms (2)

PZA sensitivity guided ultra-short all Oral Regimen

EXPERIMENTAL

The PZA sensitivity guided ultra-short 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 levofloxacin, linezolid, cycloserine, pyrazinamide, and clofazimine. Then based on molecular PZA drug sensitivity results, patients will be in divided into two sub-groups: pyrazinamide-susceptible (PZA-S) patients and pyrazinamide-resistant (PZA-R) patients. The Regimen for PZA-S patients, consisting of levofloxacin, 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 levofloxacin, linezolid, cycloserine, and clofazimine given until 36th week (prolonged to 40 or 44 weeks if no smear conversion by end of 16th and 20th week)

Drug: PZA sensitivity guided ultra-short all Oral Regimen

Standardized Shorter Regimen

ACTIVE COMPARATOR

WHO standardized shorter regimen group consists of 36-44 weeks with two phases of treatment. The first is an intensive phase of 16 weeks (extended up a maximum of 20 or 24 weeks in case of lack of smear conversion at the end of 16 or 20 weeks), and included moxifloxacin, amikacin, prothionamide, pyrazinamide, high-dose isoniazid, ethambutol and clofazimine. This is followed by a continuation phase of 20 weeks with the following agents: moxifloxacin, pyrazinamide, ethambutol and clofazimine.

Drug: Standardized Shorter Regimen

Interventions

PZA sensitivity guided ultra-short all Oral Regimen DRUG

Pyrazinamide 1500 mg daily; Levofloxacin ≤50kg 500 mg daily, \>50kg 750mg daily; Linezolid: 600 mg daily; Cycloserine ≤50kg 500 mg daily, \>50kg 750mg daily; Clofazimine 100 mg daily; All treatment is taken daily;

PZA sensitivity guided ultra-short all Oral Regimen

Standardized Shorter Regimen DRUG

Pyrazinamide 1500 mg daily;Levofloxacin 400 mg daily,; Prothionamide ≤50kg 500 mg daily, \>50kg 750mg daily; Ethambutol: ≤50kg 750 mg daily, \>50kg 1000mg daily; Clofazimine: 100 mg daily; Amikacin 600mg daily; High-dose isoniazid 600mg daily. All treatment is taken daily.

Standardized Shorter Regimen

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to participate in trial treatment and follow-up and can give informed consent 2.18-70 years old 3.Has smear-positive pulmonary tuberculosis with initial laboratory results with resistance to rifampicin confirmed by GeneXpert 4.Willing to carry out HIV testing. 5. If you are 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. 7.Willing to follow the follow-up study procedure after the follow-up.

You may not qualify if:

• Molecular drug resistance test for infected strains resistant to second-line injection;
• Molecular drug resistance assay for infected strains resistant to fluoroquinolone;
• 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;

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (13)

The Third People's Hospital of Shenzhen City

Shenzhen, Guangzhou, China

Location

Guiyang Public Health Treatment Center

Guizhou, Guizhou, China

Location

The Sixth People's Hospital of Zhengzhou

Zhengzhou, Henan, China

Location

Hunan Chest Hospital

Changsha, Hunan, China

Location

Xuzhou Infectious Disease Hospital

Xuzhou, Jiangsu, China

Location

Huashan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Shanxi Provincial Tuberculosis Control Institute

Xi’an, Shanxi, China

Location

Southwest Medical University Affiliated Hospital

Luzhou, Sichuan, China

Location

Chest Hospitalof Xinjiang Uygur Autonomous Region of PRC

Ürümqi, Xinjiang, China

Location

Hangzhou Red Cross Hospital

Hangzhou, Zhejiang, China

Location

Zhejiang Provincial Center for Disease Control and Prevention

Hangzhou, Zhejiang, China

Location

The Central Hospital of Wenzhou City

Wenzhou, Zhejiang, China

Location

Jiangxi Chest Hospital

Nanchang, China

Location

Related Publications (1)

• Weng T, Sun F, Li Y, Chen J, Chen X, Li R, Ge S, Zhao Y, Zhang W. Refining MDR-TB treatment regimens for ultra short therapy (TB-TRUST): study protocol for a randomized controlled trial. BMC Infect Dis. 2021 Feb 17;21(1):183. doi: 10.1186/s12879-021-05870-w.

  PMID: 33596848 DERIVED

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Wenhong Zhang, PhD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Division of Infectious Diseases

Study Record Dates

• First Submitted: March 6, 2019
• First Posted: March 7, 2019
• Study Start: June 1, 2020
• Primary Completion: August 10, 2024
• Study Completion: August 10, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-10

Locations

CN (13)