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

Multidrug Resistant Tuberculosis Clinical Trial

— TB-TRUSTplus  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04717908
• Other study ID #: KY1214
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 20, 2021
• Est. completion date: November 30, 2023

Study information

• Verified date: April 2023
• Source: Huashan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 vision，physical examinations and chest CT. Adverse events will be monitored and promptly managed during the whole treatment course.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 89
• Est. completion date: November 30, 2023
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Willing to participate in trial treatment and follow-up and can give informed consent

• 18-70 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 75*10^9/L;

• Have epilepsy, severe depression, irritability or psychosis;

• Alcohol abuse(drinking 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.

Related Conditions & MeSH terms

• Multidrug Resistant Tuberculosis
• Tuberculosis
• Tuberculosis, Multidrug-Resistant

Intervention

Drug:
• Bedaquiline
400 mg once daily for 2 weeks then 200mg 3 times per week;
• Pyrazinamide
1500 mg daily
• Linezolid
600 mg daily
• Cycloserine
=50kg 500 mg daily, >50kg 750mg daily;
• Clofazimine
100 mg daily;

Locations

Country	Name	City	State
China	Baoshan People's Hospital	Baoshan	Yunnan
China	Hunan Chest Hospital	Changsha	Hunan
China	Guiyang Public Health Treatment Center	Guizhou	Guizhou
China	Hangzhou Red Cross Hospital	Hangzhou	Zhejiang
China	Huaihua first people's Hospital	Huaihua	Hunan
China	Yunnan Provincial Infectious Disease Hospital	Kunming	Yunnan
China	Jiangxi Chest Hospital	Nanchang
China	Hwa Mei Hosptal,University of Chinese Academy of Sciences(Ningbo No.2 Hospital)	Ningbo	Zhejiang
China	Huashan Hospital of Fudan University	Shanghai	Shanghai
China	The Third People's Hospital of Shenzhen City	Shenzhen	Guangzhou
China	Taizhou Enze medical center Enze Hospital	Taizhou	Zhejiang
China	Chest Hospitalof Xinjiang Uygur Autonomous Region of PRC	Urumqi	Xinjiang
China	The Central Hospital of Wenzhou City	Wenzhou	Zhejiang
China	Shanxi Provincial Tuberculosis Control Institute	Xi'an	Shanxi
China	The Sixth People's Hospital of Zhengzhou	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Huashan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The median time to Sputum Culture Conversion	time from treatment initiation to the first of two consecutive negative sputum cultures without an intervening positive culture in liquid media	Time Frame: 12-36 weeks after treatment initiation
Secondary	The frequency of grade 3 or greater adverse events among patients	to access the proportion of patients who experience grade 3 or greater adverse events (graded according to the Division of AIDS severity criteria for adverse events) during treatment or follow-up;	84 weeks after treatment initiation