Multidrug Resistant Tuberculosis Clinical Trial
— GRACE-TBOfficial 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.
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.
Status | Not yet recruiting |
Enrollment | 488 |
Est. completion date | August 4, 2024 |
Est. primary completion date | August 4, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility |
Inclusion Criteria: - 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. 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 <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 - 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. |
Country | Name | City | State |
---|---|---|---|
China | Hangzhou Red Cross Hospital | Hangzhou | Zhejiang |
China | Zhejiang Provincial Center for Disease Control and Prevention | Hangzhou | Zhejiang |
China | the First Affiliated Hospital of Harbin Medical University | Harbin | Heilongjiang |
China | The Affiliated Hospital of Southwest Medical University | Luzhou | Sichuan |
China | The Second Hospital of Yinzhou of Ningbo | Ningbo | Zhejiang |
China | The Third People's Hospital of Shenzhen City | Shenzhen | Guangzhou |
China | The Fifth People's Hospital of Suzhou | Suzhou | Jiangsu |
China | Enze Medical Center of Taizhou CIty | Taizhou | Zhejiang |
China | Chest Hospitalof Xinjiang Uygur Autonomous Region of PRC | Urumqi | Xinjiang |
China | The Central Hospital of Wenzhou City | Wenzhou | Zhejiang |
China | The Sixth People's Hospital of Zhengzhou | Zhengzhou | Henan |
China | Zhuji City People's Hospital | Zhuji | Zhejaing |
Lead Sponsor | Collaborator |
---|---|
Huashan Hospital |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | 18 months after the end of treatment | |
Secondary | 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 | 18 months after the end of treatment | |
Secondary | 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; | 18 months after the end of treatment | |
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 between the NGS-guided group and conventional WHO-approved MDR-TB group; | 24 months after the start of treatment |
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