Short Course Rifapentine and Isoniazid for the Preventive Treatment of Tuberculosis(SCRIPT-TB)

Study Overview
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Brief Summary
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Tuberculosis (TB) remains the most important infectious disease in the world. Preventive treatment plays an important role in successful control of TB. The investigators' previous study showed a 3-month weekly rifapentine and isoniazid regimen had a high protective efficacy but an unsatisfactory completion rate. Therefore, the investigators suppose that a one-month (12-dose) regimen of rifapentine and isoniazid (1RPT/INH) to be equivalent to a 3-month weekly rifapentine and isoniazid regimen with similar efficacy and higher completion rate. Relevant study is lacking in China where the TB burden is high with the incidence rate of 70/100, 000. Silicosis is a risk factor of Mycobacterium tuberculosis infection. This is an open-label, non-randomized clinical trial to evaluate the efficacy and safety of the 1RPT/INH to prevent tuberculosis (TB) compared with those who do not receive preventive treatment among silicotic patients.

Detailed Description
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Tuberculosis (TB) remains the most important infectious disease in the world. Preventive treatment plays an important role in successful control of TB. For preventive therapy, alternative shortened courses such as 1-month daily rifapentine and isoniazid have been evaluated in HIV-infected individuals for its non-inferiority, safety and convenience compared with traditional monotherapy. And the treatment completion rate is higher. The investigators' previous study showed a 3-month weekly rifapentine and isoniazid regimen had a high protective efficacy but an unsatisfactory completion rate. Therefore, the investigators suppose that a one-month (12-dose) regimen of rifapentine and isoniazid (1RPT/INH) to be equivalent to a 3-month weekly rifapentine and isoniazid regimen with similar efficacy and higher completion rate. Relevant study is lacking in China where the TB burden is high with the incidence rate of 70/100, 000. Silicosis is a risk factor of Mycobacterium tuberculosis infection. This is an open-label, non-randomized clinical trial to evaluate the efficacy and safety of the 1RPT/INH to prevent tuberculosis (TB) compared with those who do not receive preventive treatment among silicotic patients.

Official Title
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Short Course Rifapentine and Isoniazid for the Preventive Treatment of Tuberculosis(SCRIPT-TB)

Conditions
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Silicosis Tuberculosis

Intervention / Treatment
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* Drug: Isoniazid；Rifapentine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals with Silica exposure or diagnosed with silicosis; Age between 18 to 65 years; Willing to provide signed informed consent, or parental consent and participant assent. Exclusion Criteria: Clinical or culture confirmed active TB; A history of treatment for > 14 consecutive days with a rifamycin or > 30 consecutive days with INH during the previous 2 years; A documented history of a completing an adequate course of treatment for active TB or latent TB infection; Allergy to Isoniazid, Rifampin, or Rifapentine; Human immunodeficiency virus (HIV) infection; History of hepatitis B/C infection or liver cirrhosis; Serum Aspartic transaminase (AST) or alanine transaminase (ALT) > 2x upper limit of normal or total bilirubin >2.5 mg/dL; Receiving immunosuppressants or biological agents; Life expectancy <3 years; Mental disorder; Participated in other clinical trials in recent three months; Other conditions that investigates consider not suitable for participate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isoniazid/ Rifapentine 3 times a week<br>Intervention：Isoniazid/ Rifapentine 3 times a week given by DOT oral Rifapentine (450mg) plus Isoniazid (400mg) for 12 doses | Drug: Isoniazid；Rifapentine<br>* 1 months (12 doses) of three-weekly rifapentine at a dose of 450mg plus isoniazid at a dose of 400mg given under direct observation<br>* Other names: 1RPT/INH 1HP;|
| No Intervention: No Intervention<br>No preventive treatment Follow up without intervention. Have already done. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative rate of culture-confirmed or clinically diagnosed TB disease in participants | Cumulative rate of culture-confirmed or clinically diagnosed TB disease in participants | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with drug discontinuation for any reason and due to adverse drug reactions associated with 1RPT/INH | Percentage of participants with drug discontinuation for any reason and due to adverse drug reactions associated with 1RPT/INH | up to 30 days after the last dose of study drug | 
| Percentage of patients with Grade 3 or 4 drug toxicities and deaths associated with 1RPT/INH | Percentage of patients with Grade 3 or 4 drug toxicities and deaths associated with 1RPT/INH | up to 30 days after the last dose of study drug | 
| Percentage of participants who complete the treatment regimen | Percentage of participants who complete the treatment regimen | Enrollment up to Month 1 (1RPT/INH) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rifapentine, isoniazid, preventive