Pulmonary Tuberculosis TB in Sputum: (+) Microscopy Clinical Trial
Official title:
Pilot Clinical Trial of PRS TB Regimen I - Phase II
Verified date | November 2020 |
Source | Shanghai Pulmonary Hospital, Shanghai, China |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Tuberculosis is the current leading cause of death due to an identifiable infectious agent worldwide. The current standard regimen for tuberculosis requires a patient to take drug combination (isoniazid, rifampicin, ethambutol, and pyrazinamide) for six to eight month periods. The purpose of this study is to compare tuberculosis treatment therapy between the current standard regimen and PRS derived combinatorial regimen. PRS derived regimen may potentially allow for a shorter course of treatment, which may reduce problems associated with adherence, toxicity, and development of drug resistance.
Status | Completed |
Enrollment | 97 |
Est. completion date | January 31, 2020 |
Est. primary completion date | December 31, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: 1. Newly diagnosed and untreated sputum smear positive tuberculosis patient 2. Pulmonary lesion consistent with TB by radiological examination 3. Positive sputum culture, identification of bacterial type confirmed Mycobacterium tuberculosis. MGIT drug sensitivity test (DST) results are sensitive of the first-line drugs (isoniazid, streptomycin, rifampicin and ethambutol). 4. Age 18 years-65 years old 5. Males or non-pregnant, non-nursing females 6. Women of child-bearing potential who are not surgically sterilized must agree to practice a barrier method of contraception or abstain from heterosexual intercourse during study drug treatment. a.Effective birth control methods: i.A double contraceptive method should be used as follows: ii.Double barrier method which can include any 2 of the following: a male condom, diaphragm, cervical cap, or female condom (male and female condoms should not be used together); or iii.Barrier method (one of the above) combined with hormone-based contraceptives or an intra-uterine device for the female subject/partner; iv.and are willing to continue practicing birth control methods throughout treatment and for 6 months (both male and female subjects) after the last dose of study medication or discontinuation from study medication in case of premature discontinuation. 7. Laboratory parameters done at or within 14 days prior to screening: 1. Serum or plasma aminotransferases (AST, ALT) less than 3 times the upper limit of normal 2. Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit of normal 3. Serum or plasma creatinine level less than or equal to 2 times the upper limit of normal 4. Serum or plasma potassium level greater than or equal to 3.5 meq/L 5. Hemoglobin level of 7.0 g/dL or greater 6. Platelet count of 100,000/mm3 or greater 7. For women of childbearing potential, a negative pregnancy test is required during screening 8. Provides written informed consent 9. Willingness and ability to attend scheduled follow-up visits and undergo study assessments. Exclusion Criteria: 1. Tuberculosis resistant to any of the study drugs (isoniazid, rifampin, EMB, PZA, CFZ, Pto) 2. Unable to take oral medications. 3. History of allergy or intolerance to any of the study drugs 4. Serum aminotransferase (AST or ALT) 3x upper limit of normal or higher 5. Pregnant or nursing females, or plan to become pregnant or nurse during the study period 6. Males planning to conceive a child during the study or within 6 months of cessation of treatment. 7. Any treatment directed against active tuberculosis within 6 months preceding initiation of study drugs. 8. Suspected or documented tuberculosis involving the central nervous system and/or bones and/or joints, and/or miliary tuberculosis and/or pericardial tuberculosis. 9. HIV infected 10. HBV infected or HCV infected (these increase the risk of TB-drug induced hepatotoxicity) 11. Weight less than 40.0 kg. 12. Known allergy or intolerance to any of the study medications. 13. Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any of the study drugs. 14. QTcF > 500 msec 15. Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest. 16. Current or planned incarceration or other involuntary detention 17. Having participated in other clinical studies with dosing of investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational study that includes treatment with medicinal agents. Subjects who are participating in observational studies or who are in a follow up period of a trial that included drug therapy may be considered for inclusion. |
Country | Name | City | State |
---|---|---|---|
China | Eighty-fifth Hospital of PLA | Shanghai | |
China | Shanghai Center for Disease Control and Prevention | Shanghai | |
China | Shanghai Public Health Clinical Center Shanghai, China | Shanghai | |
China | Shanghai Pulmonary Hospital, Shanghai, China | Shanghai |
Lead Sponsor | Collaborator |
---|---|
Shanghai Pulmonary Hospital, Shanghai, China | Bill and Melinda Gates Foundation, No.85 Hospital, Changning, Shanghai, China, Shanghai Center for Disease Control and Prevention, Shanghai Public Health Clinical Center, University of California, Los Angeles |
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The rate of sputum smear/culture negative conversion | The primary efficacy outcome is the proportion of the rate of sputum smear and culture(MGIT and LJ) negative conversion from samples collected at the end of treatment. | Group A (the standard 2HRZE/4HR regimen):at the end of Sixth months after treatment. Group B (New short course PRS regimen, 4EZ(high dose)PtoCfz) :at the end of Fourth months after treatment. | |
Secondary | Radiological manifestation change of lung TB lesions or cavity | Radiological manifestation change of lung TB lesions or cavity at the end of treatment will be compared with those before treatment(Lesion size, absorption and improvement rate, and cavity closure rate, by chest x-ray and chest CT scans). | Group A (the standard 2HRZE/4HR regimen):at the end of Sixth months after treatment. Group B (New short course PRS regimen, 4EZ(high dose)PtoCfz) :at the end of Fourth months after treatment. | |
Secondary | Number of Patients with Grade 3 or 4 Adverse Events | Using a Modified Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases [DAIDS] Scale of Adverse Event Reporting | Group A (the standard 2HRZE/4HR regimen):6 months from the beginning of clinical trials. Group B (New short course PRS regimen, 4EZ(high dose)PtoCfz) :4 months from the beginning of clinical trials. | |
Secondary | Number of Patients with TB recurrence/relapse | Number of Patients with TB recurrence/relapse by 24 months after the end of treatment(bacteriology and radiological examination confirmed). | 24 months after treatment completion for 2 groups. |