Multidrug Resistant TuberculosisGRACE-TBNCT03604848
NGS-Guided(G) Regimens(R) of Anti-tuberculosis(A) Drugs for the Control(C) and Eradication(E) of MDR-TB
A study testing WHO-approved MDR-TB regimen, NGS-guided regimen: Regimen A and NGS-guided regimen: Regimen B in people with Multidrug Resistant Tuberculosis, run by Huashan Hospital at 12 sites in China.
Trial summary
Tuberculosis (TB) has been one of the top 10 causes of death worldwide from a single infectious agent, ranking above HIV/AIDS. Management and eradication of this disease is being hindered by the emergence of multidrug-resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multidrug Resistant Tuberculosis
- What is being tested?
- WHO-approved MDR-TB regimen, NGS-guided regimen: Regimen A and NGS-guided regimen: Regimen B
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 488 participants
- Where
- 12 sitesChina
- Study dates
- 5 Aug 2018to 4 Aug 2024
- Phase
- Interventional
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who are diagnosed with active MDR-TB. MDR-TB is defined as resistance to the following two drugs: Isoniazid and Rifampicin.
- Patients who are smear positive and sputum culture positive for mycobacterium tuberculosis
- HIV negative.
- 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.
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 <150x10^9 / L, WBC < 3x10^9 / 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
Show all 14Show fewer
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
China12 sites
Hangzhou Red Cross Hospital
Hangzhou, Zhejiang
Zhejiang Provincial Center for Disease Control and Prevention
Hangzhou, Zhejiang
the First Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang
The Affiliated Hospital of Southwest Medical University
Luzhou, Sichuan
Fuli Huang, flh905@aliyun.com
The Second Hospital of Yinzhou of Ningbo
Ningbo, Zhejiang, 315040
The Third People's Hospital of Shenzhen City
Shenzhen, Guangzhou
Guofang Deng, lalaliy@sina.com
The Fifth People's Hospital of Suzhou
Suzhou, Jiangsu
Enze Medical Center of Taizhou CIty
Taizhou, Zhejiang
Zebao He, hezb@enzemed.com
Chest Hospitalof Xinjiang Uygur Autonomous Region of PRC
Ürümqi, Xinjiang
Wenlong Guan, 18999918582@189.cn
The Central Hospital of Wenzhou City
Wenzhou, Zhejiang
Xiangao Jiang, shijichan@163.com
The Sixth People's Hospital of Zhengzhou
Zhengzhou, Henan
Zhuji City People's Hospital
Zhuji, Zhejaing
Heqing Huang, zjganran@163.com
About this study
Official title: GRACE-TB：NGS-guided Regimens of Anti-tuberculosis Drugs for the Control and Eradication of MDR-TB
Tuberculosis (TB) has been one of the top 10 causes of death worldwide from a single infectious agent, ranking above HIV/AIDS. Management and eradication of this disease is being hindered by the emergence of multidrug-resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB). Globally, there were estimated 10.4 million cases of TB and 490,000 cases of MDR-TB in 2016. China accounts for around 8.6% (0.895/10.4 million) of the global TB burden, ranking third in the top 3 countries (India, Indonesia, China) with the highest number of TB cases and ranking first with the largest number of MDR/ Rifampin-Resistant (RR)-TB cases. The treatment success rate for MDR-TB using the 18-24-month conventional World Health Organization (WHO) regimen was estimated to be about 54% worldwide and 41% for China in 2016, which remains unacceptably low.
The poor MDR-TB treatment success rates suggest that current drug regimens are suboptimal. In addition, they are costly with a high pill burden, as many drugs, with significant potential for adverse events, are given for a long duration. These factors also inhibit good treatment compliance with further negative impact on treatment outcomes. According to previous studies, treatment outcomes of MDR-TB could be affected by drug resistance of pivotal drugs in MDR-TB regimen, such as fluoroquinolones, second-line injectable agents and pyrazinamide. The available drug-resistance information could help physicians decide the proper regimens for MDR-TB patients, which may prevent the useless prescription and evitable adverse.
Read more
Therefore, the individualized regimen based on the resistance profile of the bacteria and patients' drug tolerance should be aimed for high-quality treatment for MDR-TB in the future. A precision individualized treatment approach based on the rapid molecular drug susceptibility tests of second line drugs may assist clinicians in making more suitable regimen and improve the treatment outcome of MDR-TB. Also, precision regimen offers the opportunity to improve treatment of drug-resistant tuberculosis through reduced toxicity while reducing the risk of resistance amplification and further transmission at a population level.
The purpose of this research is to assess the feasibility and effects of individualized regimen that is guided by rapid molecular drug susceptibility tests of key second-line drugs through next generation sequencing. Meanwhile, the study will evaluate a short course regimens of drugs among "simple MDR-TB" patients who are proven to be sensitive to fluoroquinolones ,injectable second-line drugs and pyrazinamide.
Read the detailed description
The GRACE-TB study is a multi-center, open-label, randomized, controlled trial in patients with MDR-TB. This study will assess the feasibility and effects of individualized regimen for MDR-TB based on rapid molecular drug susceptibility tests（DSTs） of key second-line drugs through next generation sequencing (NGS) and try to improve the treatment outcome of MDR-TB. And the study will evaluate a shorter course regimen among patients who are proven to be sensitive to fluoroquinolones (FQs) or second-line injectable drugs(SLIDs) or pyrazinamide (PZA) through NGS.
A total of 488 participants with MDR-TB will be recruited and followed up until 18 months after the end of treatment. During randomization, eligible patients will be assigned in a 1:3 ratio to one of the following groups: a control group, which is treated with WHO-approved MDR-TB regimen, composed of 6 months of PZA, amikacin (Am) ,moxifloxacin (MFX), prothionamide (PTO), and Cycloserine (Cs), followed by 18 months of PZA, MFX, PTO and Cs; a NGS-guided group, which is treated with one individualized regimen that is guided by the drug susceptability test results of FQs/PZA/ SLIDs through NGS.
About 366 patients will be enrolled in the NGS-guided group. Based on the molecular DST results of FQs/PZA/ SLIDs , patients proven to be sensitive to PZA, FQs and SLIDs will be divided into to the "simple MDR-TB group" and those with resistant to at least one of FQs/PZA/ SLIDs will be divided into to "complicated MDR-TB group".
Patients in the "simple MDR-TB group" will be assigned randomly in a 1:1 ratio to one of the following daily regimen: a 9-month regimen(Regimen A) which consists of 4-month intensive therapy of PZA, Am, MFX,PTO, Cs, followed by 5-month consolidation therapy of PZA, MFX, PTO and Cs; a 12-month regimen(Regimen B) which consists of 6-month intensive therapy of PZA, Am, MFX,PTO, Cs, followed by 6-month consolidation therapy of PZA, MFX, PTO and Cs.
Patients in the "complicated MDR-TB group" will be treated a regimen (Regimen C) in which the resistant drug(s) will be replaced by the other WHO recommended drugs for MDR-TB such as linezolid, clofazimine or ethambutol based on the DST results. The duration of treatment in the "complicated MDR-TB group" is consistent with control group, with 6 months of intensive phase and 18 months of consolidation phase.
The primary objective is to compare the proportion of patients with a favorable efficacy between the NGS-guided group and the control group. The second objective is to assess whether the proportion of simple MDR-TB patients with a favorable efficacy outcome of Regimen A is not inferior to Regimen B. The participants will be followed up to 18 months after the end of the treatment. The data accrued to 18 months after the end of treatment will be used in primary and secondary analyses.
Safety evaluations performed are the routine lab tests, blood glucose, hearing, vital signs, electrocardiograph (ECG), reporting of adverse events, physical examinations and chest CT. Adverse events will be monitored and promptly managed during the whole treatment course.
- Conditions
- Multidrug Resistant Tuberculosis
- Being tested
- WHO-approved MDR-TB regimen, NGS-guided regimen: Regimen A, NGS-guided regimen: Regimen B, NGS-guided regimen: Regimen C
- Keywords
- Multidrug Resistant Tuberculosis, next generation sequencing, drug susceptibility test, precision treatment
- 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.
WHO-approved MDR-TB regimenDrug
Pyrazinamide 33-50kg 1000-1750 mg daily, 51-70kg 1750-2000 daily, >70kg 2000-2500mg daily; Amikacin 600mg daily ; Moxifloxacin 33-50kg 400 mg daily, 51-70kg 600mg daily, >70kg 800mg daily; Prothionamide 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily ; Cycloserine 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily All treatment is taken daily.
NGS-guided regimen: Regimen ADrug
Pyrazinamide 33-50kg 1000-1750 mg daily, 51-70kg 1750-2000 daily, >70kg 2000-2500mg daily; Amikacin 600mg daily ; Moxifloxacin 33-50kg 400 mg daily, 51-70kg 600mg daily, >70kg 800mg daily; Prothionamide 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily ; Cycloserine 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily All treatment is taken daily.
NGS-guided regimen: Regimen BDrug
Pyrazinamide 33-50kg 1000-1750 mg daily, 51-70kg 1750-2000 daily, >70kg 2000-2500mg daily; Amikacin 600mg daily ; Moxifloxacin 33-50kg 400 mg daily, 51-70kg 600mg daily, >70kg 800mg daily; Prothionamide 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily ; Cycloserine 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily All treatment is taken daily.
NGS-guided regimen: Regimen CDrug
Based on the drug susceptibility test results, the resistant drug(s) will be replaced by the other WHO recommended drugs for MDR-TB such as linezolid, clofazimine or ethambutol.
The dose of linezolid, clofazimine or ethambutol as follows:
Linezolid: 600 mg daily, clofazamine: 33-50kg 50 mg daily, 51-70kg 100 daily, >70kg 100 mg daily; ethambutol: 33-50kg 800 mg daily, 51-70kg 800 daily, >70kg 1200 mg daily;
| Study group | Role | What they receive |
|---|---|---|
| NGS-guided regimen: Regimen A | Experimental | Regimen A: 9-month regimen for simple MDR-TB patients 4 months of pyrazinamide, amikacin ,moxifloxacin, prothionamide, and cycloserine , followed by 5months of pyrazinamide,moxifloxacin, prothionamide, and cycloserine Receives: Drug: NGS-guided regimen: Regimen A |
| NGS-guided regimen: Regimen B | Experimental | Regimen B: 12-month simple MDR-TB regimen for simple MDR-TB patients 6 months of pyrazinamide, amikacin ,moxifloxacin, prothionamide, and cycloserine , followed by 6 months of pyrazinamide,moxifloxacin, prothionamide, and cycloserine Receives: Drug: NGS-guided regimen: Regimen B |
| NGS-guided regimen: Regimen C | Experimental | Regimen C : for complicated MDR-TB patients In regimen C, the resistant drug(s) will be replaced by the other WHO recommended drugs for MDR-TB such as linezolid, clofazimine or ethambutol based on the drug susceptibility test results. The duration of treatment in the "complicated MDR-TB group" is consistent with control group, with 6 months of intensive phase and 18 months of consolidation phase. Receives: Drug: NGS-guided regimen: Regimen C |
| WHO-approved MDR-TB regimen | Active comparator | 6 months of pyrazinamide, amikacin,moxifloxacin, prothionamide , and cycloserine , followed by 18 months of pyrazinamide, moxifloxacin, prothionamide , and cycloserine Receives: Drug: WHO-approved MDR-TB regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of NGS-guided treatment(the proportion of patients with a favorable efficacy outcome 18 months after the end of treatment)
to compare the proportion of patients with a favorable efficacy outcome between the NGS-guided group and conventional WHO-approved MDR-TB group
Measured: 18 months after the end of treatment
Secondary outcomes (3)
Efficacy of shorter course regimen for simple MDR-TB patients(the proportion of patients with a favorable efficacy outcome between regimen A and regimen B)
to assess whether the proportion of simple MDR-TB patients with a favorable efficacy outcome of Regimen A is not inferior to Regimen B
Measured: 18 months after the end of treatment
Safety(the proportion of patients who experience grade 3 or greater adverse events)
to compare 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, on the experimental regimen when compared to the control regimen;
Measured: 18 months after the end of treatment
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 between the NGS-guided group and conventional WHO-approved MDR-TB group;
Measured: 24 months after the start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2018
- Study start5 Aug 2018 (estimated)
- Primary completion4 Aug 2024 (estimated)
- Study completion4 Aug 2024 (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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 488 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
- Wenhong Zhang, PhD,MD, Principal investigator, Huashan Hospital of Fudan University, Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03604848
- Sponsor's protocol ID
- KY2018-291
- Acronym
- GRACE-TB
- Status last verified
- Jul 2018
- First submitted
- 26 Jun 2018
- Last updated
- 30 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GRACE-TB：NGS-guided Regimens of Anti-tuberculosis Drugs for the Control and Eradication of MDR-TB
- ClinicalTrials.gov ID
- NCT03604848
- Acronym / sponsor ID
- GRACE-TB / KY2018-291
- Conditions
- Multidrug Resistant Tuberculosis
- Keywords
- Multidrug Resistant Tuberculosis, next generation sequencing, drug susceptibility test, precision treatment
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 488 participants (estimated)
- Lead sponsor
- Huashan HospitalUniversity, hospital or other
- Study start
- 5 Aug 2018 (estimated)
- Primary completion
- 4 Aug 2024 (estimated)
- Study completion
- 4 Aug 2024 (estimated)
- First posted
- 30 Jul 2018 (actual)
- 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.
Tuberculosis (TB) has been one of the top 10 causes of death worldwide from a single infectious agent, ranking above HIV/AIDS. Management and eradication of this disease is being hindered by the emergence of multidrug-resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB). Globally, there were estimated 10.4 million cases of TB and 490,000 cases of MDR-TB in 2016. China accounts for around 8.6% (0.895/10.4 million) of the global TB burden, ranking third in the top 3 countries (India, Indonesia, China) with the highest number of TB cases and ranking first with the largest number of MDR/ Rifampin-Resistant (RR)-TB cases. The treatment success rate for MDR-TB using the 18-24-month conventional World Health Organization (WHO) regimen was estimated to be about 54% worldwide and 41% for China in 2016, which remains unacceptably low.
The poor MDR-TB treatment success rates suggest that current drug regimens are suboptimal. In addition, they are costly with a high pill burden, as many drugs, with significant potential for adverse events, are given for a long duration. These factors also inhibit good treatment compliance with further negative impact on treatment outcomes. According to previous studies, treatment outcomes of MDR-TB could be affected by drug resistance of pivotal drugs in MDR-TB regimen, such as fluoroquinolones, second-line injectable agents and pyrazinamide. The available drug-resistance information could help physicians decide the proper regimens for MDR-TB patients, which may prevent the useless prescription and evitable adverse.
Therefore, the individualized regimen based on the resistance profile of the bacteria and patients' drug tolerance should be aimed for high-quality treatment for MDR-TB in the future. A precision individualized treatment approach based on the rapid molecular drug susceptibility tests of second line drugs may assist clinicians in making more suitable regimen and improve the treatment outcome of MDR-TB. Also, precision regimen offers the opportunity to improve treatment of drug-resistant tuberculosis through reduced toxicity while reducing the risk of resistance amplification and further transmission at a population level.
The purpose of this research is to assess the feasibility and effects of individualized regimen that is guided by rapid molecular drug susceptibility tests of key second-line drugs through next generation sequencing. Meanwhile, the study will evaluate a short course regimens of drugs among "simple MDR-TB" patients who are proven to be sensitive to fluoroquinolones ,injectable second-line drugs and pyrazinamide.
Detailed description
The GRACE-TB study is a multi-center, open-label, randomized, controlled trial in patients with MDR-TB. This study will assess the feasibility and effects of individualized regimen for MDR-TB based on rapid molecular drug susceptibility tests（DSTs） of key second-line drugs through next generation sequencing (NGS) and try to improve the treatment outcome of MDR-TB. And the study will evaluate a shorter course regimen among patients who are proven to be sensitive to fluoroquinolones (FQs) or second-line injectable drugs(SLIDs) or pyrazinamide (PZA) through NGS.
A total of 488 participants with MDR-TB will be recruited and followed up until 18 months after the end of treatment. During randomization, eligible patients will be assigned in a 1:3 ratio to one of the following groups: a control group, which is treated with WHO-approved MDR-TB regimen, composed of 6 months of PZA, amikacin (Am) ,moxifloxacin (MFX), prothionamide (PTO), and Cycloserine (Cs), followed by 18 months of PZA, MFX, PTO and Cs; a NGS-guided group, which is treated with one individualized regimen that is guided by the drug susceptability test results of FQs/PZA/ SLIDs through NGS.
About 366 patients will be enrolled in the NGS-guided group. Based on the molecular DST results of FQs/PZA/ SLIDs , patients proven to be sensitive to PZA, FQs and SLIDs will be divided into to the "simple MDR-TB group" and those with resistant to at least one of FQs/PZA/ SLIDs will be divided into to "complicated MDR-TB group".
Patients in the "simple MDR-TB group" will be assigned randomly in a 1:1 ratio to one of the following daily regimen: a 9-month regimen(Regimen A) which consists of 4-month intensive therapy of PZA, Am, MFX,PTO, Cs, followed by 5-month consolidation therapy of PZA, MFX, PTO and Cs; a 12-month regimen(Regimen B) which consists of 6-month intensive therapy of PZA, Am, MFX,PTO, Cs, followed by 6-month consolidation therapy of PZA, MFX, PTO and Cs.
Patients in the "complicated MDR-TB group" will be treated a regimen (Regimen C) in which the resistant drug(s) will be replaced by the other WHO recommended drugs for MDR-TB such as linezolid, clofazimine or ethambutol based on the DST results. The duration of treatment in the "complicated MDR-TB group" is consistent with control group, with 6 months of intensive phase and 18 months of consolidation phase.
The primary objective is to compare the proportion of patients with a favorable efficacy between the NGS-guided group and the control group. The second objective is to assess whether the proportion of simple MDR-TB patients with a favorable efficacy outcome of Regimen A is not inferior to Regimen B. The participants will be followed up to 18 months after the end of the treatment. The data accrued to 18 months after the end of treatment will be used in primary and secondary analyses.
Safety evaluations performed are the routine lab tests, blood glucose, hearing, vital signs, electrocardiograph (ECG), reporting of adverse events, physical examinations and chest CT. Adverse events will be monitored and promptly managed during the whole treatment course.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NGS-guided regimen: Regimen A | Experimental | Drug: NGS-guided regimen: Regimen ARegimen A: 9-month regimen for simple MDR-TB patients 4 months of pyrazinamide, amikacin ,moxifloxacin, prothionamide, and cycloserine , followed by 5months of pyrazinamide,moxifloxacin, prothionamide, and cycloserine |
| NGS-guided regimen: Regimen B | Experimental | Drug: NGS-guided regimen: Regimen BRegimen B: 12-month simple MDR-TB regimen for simple MDR-TB patients 6 months of pyrazinamide, amikacin ,moxifloxacin, prothionamide, and cycloserine , followed by 6 months of pyrazinamide,moxifloxacin, prothionamide, and cycloserine |
| NGS-guided regimen: Regimen C | Experimental | Drug: NGS-guided regimen: Regimen CRegimen C : for complicated MDR-TB patients In regimen C, the resistant drug(s) will be replaced by the other WHO recommended drugs for MDR-TB such as linezolid, clofazimine or ethambutol based on the drug susceptibility test results. The duration of treatment in the "complicated MDR-TB group" is consistent with control group, with 6 months of intensive phase and 18 months of consolidation phase. |
| WHO-approved MDR-TB regimen | Active comparator | Drug: WHO-approved MDR-TB regimen6 months of pyrazinamide, amikacin,moxifloxacin, prothionamide , and cycloserine , followed by 18 months of pyrazinamide, moxifloxacin, prothionamide , and cycloserine |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients who are diagnosed with active MDR-TB. MDR-TB is defined as resistance to the following two drugs: Isoniazid and Rifampicin.
- Patients who are smear positive and sputum culture positive for mycobacterium tuberculosis
- HIV negative.
- 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 <150x10^9 / L, WBC < 3x10^9 / L.
- Abnormal ECG (Male patients with prolonged QT interval exceeding 430ms,
- Female patients with prolonged QT interval exceeding 450ms)
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 |
|---|---|---|
| WHO-approved MDR-TB regimenPyrazinamide 33-50kg 1000-1750 mg daily, 51-70kg 1750-2000 daily, >70kg 2000-2500mg daily; Amikacin 600mg daily ; Moxifloxacin 33-50kg 400 mg daily, 51-70kg 600mg daily, >70kg 800mg daily; Prothionamide 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily ; Cycloserine 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily All treatment is taken daily. | Drug | WHO-approved MDR-TB regimen |
| NGS-guided regimen: Regimen APyrazinamide 33-50kg 1000-1750 mg daily, 51-70kg 1750-2000 daily, >70kg 2000-2500mg daily; Amikacin 600mg daily ; Moxifloxacin 33-50kg 400 mg daily, 51-70kg 600mg daily, >70kg 800mg daily; Prothionamide 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily ; Cycloserine 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily All treatment is taken daily. | Drug | NGS-guided regimen: Regimen A |
| NGS-guided regimen: Regimen BPyrazinamide 33-50kg 1000-1750 mg daily, 51-70kg 1750-2000 daily, >70kg 2000-2500mg daily; Amikacin 600mg daily ; Moxifloxacin 33-50kg 400 mg daily, 51-70kg 600mg daily, >70kg 800mg daily; Prothionamide 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily ; Cycloserine 33-50kg 500 mg daily, 51-70kg 750 daily, >70kg 1000 mg daily All treatment is taken daily. | Drug | NGS-guided regimen: Regimen B |
| NGS-guided regimen: Regimen CBased on the drug susceptibility test results, the resistant drug(s) will be replaced by the other WHO recommended drugs for MDR-TB such as linezolid, clofazimine or ethambutol. The dose of linezolid, clofazimine or ethambutol as follows: Linezolid: 600 mg daily, clofazamine: 33-50kg 50 mg daily, 51-70kg 100 daily, >70kg 100 mg daily; ethambutol: 33-50kg 800 mg daily, 51-70kg 800 daily, >70kg 1200 mg daily; | Drug | NGS-guided regimen: Regimen C |
Primary outcome
Efficacy of NGS-guided treatment(the proportion of patients with a favorable efficacy outcome 18 months after the end of treatment)
Time frame: 18 months after the end of treatment
to compare the proportion of patients with a favorable efficacy outcome between the NGS-guided group and conventional WHO-approved MDR-TB group
3 secondary outcomes
Efficacy of shorter course regimen for simple MDR-TB patients(the proportion of patients with a favorable efficacy outcome between regimen A and regimen B)
Time frame: 18 months after the end of treatment
Safety(the proportion of patients who experience grade 3 or greater adverse events)
Time frame: 18 months after the end of treatment
The Median Time to Sputum Culture Conversion
Time frame: 24 months after the start of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2018.
Related trials for Multidrug Resistant Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR
RecruitingObservational study
Molecular Epidemiology, Strains Genotyping of Multi-drug Resistant Tuberculosis Circulating in Central Africa Region
Multidrug-resistant Tuberculosis (MDR-TB)
RecruitingObservational study
Training Protocol on the Natural History of Tuberculosis
Mycobacterium Infections, Tuberculosis, Multidrug-Resistant
Recruiting
Bring BPaL2Me Trial Comparing Nurse-Led RR-TB Treatment to Physician-Led RR-TB Treatment
Drug Resistant Tuberculosis
RecruitingPhase 3
A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis
Rifampicin-Resistant Pulmonary Tuberculosis, Multidrug-Resistant Pulmonary Tuberculosis
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.
Wenhong Zhang, PhD,MD principal investigator
Huashan Hospital of Fudan University, Shanghai, China
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing WHO-approved MDR-TB regimen, NGS-guided regimen: Regimen A and NGS-guided regimen: Regimen B in people with Multidrug Resistant Tuberculosis, run by Huashan Hospital at 12 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 4 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 30 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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.
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?
Efficacy of NGS-guided treatment(the proportion of patients with a favorable efficacy outcome 18 months after the end of treatment) (time frame: 18 months after the end of treatment). 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 30 Jul 2018.