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

NCT04717908 | Completed DMC

• 1 other identifier: KY1214
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 15

Brief 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 .

Conditions

Multidrug Resistant Tuberculosis

Keywords

Multidrug resistant tuberculosis; shorter treatment; all-oral regimen; PZA sensitivity

Outcome Measures

Primary Outcomes (1)

• Treatment success rate

  To access the treatment success rate without relapse .Treatment outcomes will be classified into favourable outcome and unfavourable outcome.

  84 weeks after the treatment initiation

Secondary Outcomes (2)

• The median time to Sputum Culture Conversion

  Time Frame: 12-36 weeks after treatment initiation

• The frequency of grade 3 or greater adverse events among patients

  84 weeks after treatment initiation

Study Arms (1)

PZA sensitivity guided all oral regimen

EXPERIMENTAL

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 divided into three sub-groups. 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) .

Drug: Bedaquiline; Drug: Pyrazinamide; Drug: Linezolid; Drug: Cycloserine; Drug: Clofazimine

Interventions

Bedaquiline DRUG

400 mg once daily for 2 weeks then 200mg 3 times per week;

Also known as: BDQ

PZA sensitivity guided all oral regimen

Pyrazinamide DRUG

1500 mg daily

Also known as: PZA

PZA sensitivity guided all oral regimen

Linezolid DRUG

600 mg daily

Also known as: LZD

PZA sensitivity guided all oral regimen

Cycloserine DRUG

≤50kg 500 mg daily, \>50kg 750mg daily;

Also known as: Cs

PZA sensitivity guided all oral regimen

Clofazimine DRUG

100 mg daily;

Also known as: CFZ

PZA sensitivity guided all oral 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
• 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.

You may not qualify if:

• 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 75\*10\^9/L;
• Have epilepsy, severe depression, irritability or psychosis；

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (15)

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

Huaihua first people's Hospital

Huaihua, Hunan, China

Location

Huashan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Shanxi Provincial Tuberculosis Control Institute

Xi’an, Shanxi, China

Location

Chest Hospitalof Xinjiang Uygur Autonomous Region of PRC

Ürümqi, Xinjiang, China

Location

Baoshan People's Hospital

Baoshan, Yunnan, China

Location

Yunnan Provincial Infectious Disease Hospital

Kunming, Yunnan, China

Location

Hangzhou Red Cross Hospital

Hangzhou, Zhejiang, China

Location

Hwa Mei Hosptal,University of Chinese Academy of Sciences(Ningbo No.2 Hospital)

Ningbo, Zhejiang, China

Location

Taizhou Enze medical center Enze Hospital

Taizhou, Zhejiang, China

Location

The Central Hospital of Wenzhou City

Wenzhou, Zhejiang, China

Location

Jiangxi Chest Hospital

Nanchang, China

Location

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

bedaquiline; Pyrazinamide; Linezolid; Cycloserine; Clofazimine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Isoxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Phenazines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Wenhong Zhang, PhD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Division of Infectious Diseases

Study Record Dates

• First Submitted: January 17, 2021
• First Posted: January 22, 2021
• Study Start: January 20, 2021
• Primary Completion: June 22, 2024
• Study Completion: June 22, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (15)