Multidrug Resistant TuberculosisPhase 3NCT02120638
Optimization of MDR-TB Treatment Regimen Based on the Molecular Drug Susceptibility Results of Pyrazinamide
A Phase 3 study testing Pyrazinamide containing regimen and Regimen without Pyrazinamide in people with Multidrug Resistant Tuberculosis, run by Huashan Hospital at 11 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multidrug Resistant Tuberculosis
- What is being tested?
- Pyrazinamide containing regimen and Regimen without Pyrazinamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 11 sitesChina
- Study dates
- Apr 2014to Apr 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
China11 sites, 8 recruiting
- Recruiting
Chongqing Pulmonary Hospital
Chongqing, Chongqing Municipality
Xiyan Zhang, 593189393@qq.com
- Recruiting
Hangzhou Red Cross Hospital
Hangzhou, Zhejiang
Yunfeng Sheng, shengyf617@163.com
- Active, not recruiting
The Affiliated Hospital of Hangzhou Normal University
Hangzhou, Zhejiang
- Recruiting
The Affiliated Hospital of Luzhou Medical College
Huzhou, Zhejiang
Fuli Huang, 10111220006@fudan.edu.cn
- Recruiting
The Fifth People's Hospital of Suzhou
Suzhou, Jiangsu
Peijun Tang, tangpeipei001@163.com
- Active, not recruiting
Wenling No.1 People's Hospital
Taizhou, Zhejiang
- Active, not recruiting
Xinjiang Chest Hospital
Ürümqi, Xinjiang
- Recruiting
Ruian People's Hospital
Wenzhou, Zhejiang
Dong Zhang, 418022491@qq.com
- Recruiting
The Fifth People's Hospital of Wuxi
Wuxi, Jiangsu
Qinlao Ou, oqinfang@163.com
- Recruiting
The Sixth People's Hospital of Zhengzhou
Zhengzhou, Henan
Yu Chen, chenyuhnzz@163.com
- Recruiting
Zhuji People's Hospital of Zhejiang Province
Zhuji, Zhejiang
Heqing Huang, zjganran@163.com
About this study
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.
Read the 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.
- Conditions
- Multidrug Resistant Tuberculosis
- Being tested
- Pyrazinamide containing regimen, Regimen without Pyrazinamide
- Keywords
- Multidrug Resistant Tuberculosis, Pyrazinamide
- Medical subject headings
- Tuberculosis, Multidrug-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyrazinamide containing regimenDrug
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.
Regimen without PyrazinamideDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Regimen without Pyrazinamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Median Time to Sputum Culture Conversion
Measured: 24 months
Secondary outcomes (1)
The Percentage of treatment success
Treatment success is defined as：
- During the last 12 months of treatment，participants have at least 5 sputum cultures negative taken at least 30 days apart.
- During the last 12 months of treatment，participants have only one sputum culture positive, followed by at least 3 consecutive sputum cultures negative taken at least 30 days apart, without symptoms progression.
- Participants complete the treatment, but less than 5 culture results are available.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2014 (estimated)
- Study startApr 2014
- Primary completionApr 2016 (estimated)
- Study completionApr 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multidrug Resistant TuberculosisStudies of the same condition, open and under way.
- More trials run by Huashan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huashan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wen-hong Zhang, Huashan Hospital
- Investigators
- Ying Zhang, PhD, Principal investigator, Huashan Hospital of Fudan University, Shanghai, China;Johns Hopkins University, Baltimore, Maryland, USAWenhong Zhang, PhD,MD, Principal investigator, Huashan Hospital of Fudan University, Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02120638
- Sponsor's protocol ID
- KY2013-260
- Other IDs
- 2013ZX10003008-003
- Status last verified
- Apr 2014
- First submitted
- 21 Apr 2014
- Last updated
- 23 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of MDR-TB Treatment Regimen Based on the Molecular Drug Susceptibility Results of Pyrazinamide
- ClinicalTrials.gov ID
- NCT02120638
- Acronym / sponsor ID
- KY2013-260
- Conditions
- Multidrug Resistant Tuberculosis
- Keywords
- Multidrug Resistant Tuberculosis, Pyrazinamide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Huashan HospitalUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Apr 2016 (estimated)
- Study completion
- Apr 2016 (estimated)
- First posted
- 23 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pyrazinamide Sensitive Comparator | Active comparator | Drug: Pyrazinamide containing regimenPyrazinamide 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 |
| Pyrazinamide Resistant Comparator | Experimental | Drug: Regimen without PyrazinamideRegimen 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 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pyrazinamide containing regimenPyrazinamide 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. | Drug | Pyrazinamide Sensitive Comparator |
| Regimen without PyrazinamideIsoniazid 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. | Drug | Pyrazinamide Resistant Comparator |
Primary outcome
The Median Time to Sputum Culture Conversion
Time frame: 24 months
1 secondary outcome
The Percentage of treatment success
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ying Zhang, PhD principal investigator
Huashan Hospital of Fudan University, Shanghai, China;Johns Hopkins University, Baltimore, Maryland, USA
Wenhong Zhang, PhD,MD principal investigator
Huashan Hospital of Fudan University, Shanghai, China
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pyrazinamide containing regimen and Regimen without Pyrazinamide in people with Multidrug Resistant Tuberculosis, run by Huashan Hospital at 11 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wenhong Zhang, PhD,MD (+86 21 52889999 ext. 8123, zhangwenhong@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Median Time to Sputum Culture Conversion (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2014.