Optimization of MDR-TB Treatment Regimen Based on the Molecular Drug Susceptibility Results of Pyrazinamide
Information source: Huashan Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multidrug Resistant Tuberculosis
Intervention: Pyrazinamide containing regimen (Drug); Regimen without Pyrazinamide (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Huashan Hospital Official(s) and/or principal investigator(s): Ying Zhang, PhD, Principal Investigator, Affiliation: Huashan Hospital of Fudan University, Shanghai, China;Johns Hopkins University, Baltimore, Maryland, USA Wenhong Zhang, PhD,MD, Principal Investigator, Affiliation: Huashan Hospital of Fudan University, Shanghai, China
Overall contact: Wenhong Zhang, PhD,MD, Phone: +86 21 52889999, Ext: 8123, Email: zhangwenhong@fudan.edu.cn
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.
Clinical Details
Official title: Optimization of MDR-TB Treatment Regimen Based on the Molecular Drug Susceptibility Results of Pyrazinamide
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The Median Time to Sputum Culture Conversion
Secondary outcome: The Percentage of treatment success
Detailed description:
This is a phase 3, open labeled, prospective cohort study to evaluate the molecular testing
of pyrazinamide susceptibility in optimizing the MDR-TB treatment regimen. Approximately 100
participants will be given the molecular detection of pncA and rpsA mutations and divide
into to the pyrazinamide sensitive comparator group and the pyrazinamide resistant group
based on the susceptibility results. For the pyrazinamide sensitive group, the regimen
contains six months of chemotherapy with pyrazinamide, amikacin, levofloxacin, plus
prothionamide, followed by six months of pyrazinamide, levofloxacin, clarithromycin, plus
prothionamide. For the pyrazinamide resistant group, the regimen contains six months of
chemotherapy with isoniazid, amikacin, levofloxacin, plus prothionamide, followed by
eighteen months of isoniazid, levofloxacin, clarithromycin, plus prothionamide.
The participants will be followed up to 24 months after the start of the treatment. The
primary outcome is the sputum culture conversion and the adverse events. Safety evaluations
that will be performed are the routine lab tests, blood glucose, hearing , vital signs, ECG,
reporting of adverse events, physical examinations and X-rays.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Locations and Contacts
Wenhong Zhang, PhD,MD, Phone: +86 21 52889999, Ext: 8123, Email: zhangwenhong@fudan.edu.cn
Chongqing Pulmonary Hospital, Chongqing, Chongqing, China; Recruiting Xiyan Zhang, Email: 593189393@qq.com
The Sixth People's Hospital of Zhengzhou, Zhengzhou, Henan, China; Recruiting Yu Chen, Email: chenyuhnzz@163.com
The Fifth People's Hospital of Suzhou, Suzhou, Jiangsu, China; Recruiting Peijun Tang, Email: tangpeipei001@163.com
The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu, China; Recruiting Qinlao Ou, Email: oqinfang@163.com
Xinjiang Chest Hospital, Urumqi, Xinjiang, China; Active, not recruiting
Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, China; Recruiting Yunfeng Sheng, Email: shengyf617@163.com
The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China; Active, not recruiting
The Affiliated Hospital of Luzhou Medical College, Huzhou, Zhejiang, China; Recruiting Fuli Huang, Email: 10111220006@fudan.edu.cn
Wenling No.1 People's Hospital, Taizhou, Zhejiang, China; Active, not recruiting
Ruian People's Hospital, Wenzhou, Zhejiang, China; Recruiting Dong Zhang, Email: 418022491@qq.com
Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang, China; Recruiting Heqing Huang, Email: zjganran@163.com
Additional Information
Starting date: April 2014
Last updated: April 21, 2014
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