Optimization of MDR-TB Treatment Regimen Based on the Molecular Drug Susceptibility Results of Pyrazinamide

NCT02120638 | Unknown Phase 3 DMC

• 2 other identifiers: KY2013-2602013ZX10003008-003
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 11

Brief Summary

Multidrug resistant tuberculosis (MDR-TB) is difficult to treat and raises a great challenge to TB control program. That pyrazinamide can shorten the course of treatment and facilitate bacilli clearance has been proved recently. In 2011, WHO recommended to use pyrazinamide throughout the course of treatment for MDR-TB. However, pyrazinamide susceptibility testing has not been widely used in clinic. And the conventional testing is time-consuming and unreliable. In contrast, the detection of pncA and rpsA mutations with molecular methods can provide rapid results of pyrazinamide susceptibility. The purpose of this study is to evaluate the efficacy of the introduce the molecular testing of pyrazinamide susceptibility in optimizing the MDR-TB treatment regimen.

Conditions

Multidrug Resistant Tuberculosis

Keywords

Multidrug Resistant Tuberculosis; Pyrazinamide

Outcome Measures

Primary Outcomes (1)

• The Median Time to Sputum Culture Conversion

  24 months

Secondary Outcomes (1)

• The Percentage of treatment success

  24 months

Study Arms (2)

Pyrazinamide Sensitive Comparator

ACTIVE COMPARATOR

Pyrazinamide containing regimen: Regimen B1 - 6ZAmkLfxClrPto\\6ZlfxClrPto * Six months of chemotherapy with Pyrazinamide,Amikacin,Levofloxacin,Clarithromycin,plus Prothionamide,followed by * Six months of Pyrazinamide,Levofloxacin,Clarithromycin,plus Prothionamide

Drug: Pyrazinamide containing regimen

Pyrazinamide Resistant Comparator

EXPERIMENTAL

Regimen without Pyrazinamide: Regimen B2 - 6HAmkLfxClrPto\\18HlfxClrPto * Six months of chemotherapy with Isoniazid,Amikacin,Levofloxacin,Clarithromycin,plus Prothionamide,followed by * Eighteen months of Isoniazid,Levofloxacin,Clarithromycin,plus Prothionamide

Drug: Regimen without Pyrazinamide

Interventions

Pyrazinamide containing regimen DRUG

Pyrazinamide 33-50kg 1000-1750 mg daily, 51-70kg 1750-2000 daily, \>70kg 2000-2500mg daily Amikacin 600mg daily Levofloxacin 33-70kg 750 mg daily, \>70kg 1000 mg daily Clarithromycin 33-50kg 500 mg daily, \>50kg 1000 mg daily Prothionamide 33-50kg 500 mg daily, 51-70kg 750 daily, \>70kg 1000 mg daily All treatment is taken daily, for a duration of up to 12 months depending on treatment arm.

Pyrazinamide Sensitive Comparator

Regimen without Pyrazinamide DRUG

Isoniazid 600mg daily Amikacin 600mg daily Levofloxacin 33-70kg 750 mg daily, \>70kg 1000 mg daily Clarithromycin 33-50kg 500 mg daily, \>50kg 1000 mg daily Prothionamide 33-50kg 500 mg daily, 51-70kg 750 daily, \>70kg 1000 mg daily All treatment is taken daily, for a duration of up to 18 months depending on treatment arm.

Pyrazinamide Resistant Comparator

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients who are diagnosed with active tuberculosis
• Patients who are smear positive and sputum culture positive for tuberculosis
• History of active tuberculosis less than 3 years
• With less than 2 times of previous antituberculous therapy
• The patients should be voluntarily entering the study and willing to sign up the consent form after full knowledge of the risks, schedule, drug features of this study.
• MDR-TB is defined as resistance to the following two drugs: Isoniazid and Rifampicin.
• Extensively drug-resistant(XDR-TB) is defined as resistance to any flouroquinolones and any one of the three second-line antituberculous injections (capreomycin, kanamycin, amikacin)
• The study enrolled MDR-TB subjects and excluded XDR-TB subjects. If MDR-TB subjects is also resistant to flouroquinolones or capreomycin( kanamycin, amikacin), the subjects is included in the study as pre-XDR TB patients.

You may not qualify if:

• Known allergy or intolerance to the drugs in this study
• Liver damage (Hepatic encephalopathy; ascites; prothrombin time prolonged 2 seconds compared with normal controls; blood bilirubin 3 times greater than the upper limit of the normal range)
• Platelets \<150x109 / L, WBC \< 3x109 / L.
• Abnormal ECG (Male patients with prolonged QT interval exceeding 430ms, Female patients with prolonged QT interval exceeding 450ms)
• Serum creatinine 1.5 times higher than upper limit
• Fasting blood-glucose higher than 8.0 mmol/L
• Patients who are on medication that effect the results of the drugs in this study
• Karnofsky score\<50% (see appendix)
• Women who are pregnant or breastfeeding
• HIV positive
• Participating in other clinical trials in the past three months
• Patients with mental illness and severe neurosis
• Patients who have poor compliances
• Any special circumstances in which the research physicians believe that is not suitable for this study.

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (11)

Chongqing Pulmonary Hospital

Chongqing, Chongqing Municipality, China

RECRUITING

The Sixth People's Hospital of Zhengzhou

Zhengzhou, Henan, China

RECRUITING

The Fifth People's Hospital of Suzhou

Suzhou, Jiangsu, China

RECRUITING

The Fifth People's Hospital of Wuxi

Wuxi, Jiangsu, China

RECRUITING

Xinjiang Chest Hospital

Ürümqi, Xinjiang, China

ACTIVE NOT RECRUITING

Hangzhou Red Cross Hospital

Hangzhou, Zhejiang, China

RECRUITING

The Affiliated Hospital of Hangzhou Normal University

Hangzhou, Zhejiang, China

ACTIVE NOT RECRUITING

The Affiliated Hospital of Luzhou Medical College

Huzhou, Zhejiang, China

RECRUITING

Wenling No.1 People's Hospital

Taizhou, Zhejiang, China

ACTIVE NOT RECRUITING

Ruian People's Hospital

Wenzhou, Zhejiang, China

RECRUITING

Zhuji People's Hospital of Zhejiang Province

Zhuji, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

Clinical Protocols; Pyrazinamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ying Zhang, PhD

  Huashan Hospital of Fudan University, Shanghai, China;Johns Hopkins University, Baltimore, Maryland, USA

  PRINCIPAL INVESTIGATOR

• Wenhong Zhang, PhD,MD

  Huashan Hospital of Fudan University, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wenhong Zhang, PhD,MD

CONTACT

+86 21 52889999; zhangwenhong@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON 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: April 21, 2014
• First Posted: April 23, 2014
• Study Start: April 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: April 23, 2014

Record last verified: 2014-04

Locations

CN (11)