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Efficacy of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention

Phase 3
Completed
Conditions
Silicosis
Tuberculosis
Interventions
Drug: Weekly INH / RRT given by DOT
Registration Number
NCT02430259
Lead Sponsor
Huashan Hospital
Brief Summary

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, the three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) are now recommended by WHO for its non-inferiority, safety and convenience compared with 6\~9 months regimen of daily isoniazid monotherapy or 3\~4 months daily rifampicin monotherapy. And the treatment completion rate is higher compared with daily regimen. However, relevant study is lacking in China where the TB burden is high with the incidence rate of 70/100, 000. And the provision of chemoprophylaxis is not recommended in China currently.

Silicosis is a high risk factor of Mycobacterium tuberculosis infection. This is an open-label, randomized, Phase III clinical trial to evaluate the effectiveness and tolerability of the 3RPT/INH to prevent tuberculosis (TB) compared with those who do not receive preventive treatment among silicotic patients.

Detailed Description

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, the three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) are now recommended by WHO for its non-inferiority, safety and convenience compared with 6\~9 months regimen of daily isoniazid monotherapy or 3\~4 months daily rifampicin monotherapy. And the treatment completion rate is higher compared with daily regimen. However, relevant study is lacking in China where the TB burden is high with the incidence rate of 70/100, 000.

Silicosis is a high risk factor of Mycobacterium tuberculosis infection. This is an open-label, randomized, Phase III clinical trial to evaluate the effectiveness and tolerability of the 3RPT/INH to prevent tuberculosis (TB) among silicotic patients.

The PRIMARY objective of this open-label, randomized, Phase III clinical trial is to evaluate the effectiveness of the 3RPT/INH to prevent TB compared with those who do not receive preventive treatment among eligible silicotic patients.

The SECONDARY objective:

Describe the safety profile of 3RPT/INH in China (the rates of drug discontinuation for any reason and due to adverse drug reactions associated with 3RPT/INH, the rates of any grade 3, 4, or 5 drug toxicity associated with 3RPT/INH) Describe the treatment completion rates of 3RPT/INH. Describe patterns of antibiotic resistance of M. tuberculosis isolates in patients who develop TB despite preventive treatment.

Compare the results of QuantiFERON Gold In-Tube before and after preventive treatment.

For assessment of the primary outcome, development of TB, a sample size of approximately 280 persons per arm will be required with 3 years follow-up.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
566
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Weekly Isoniazid / RifapentineWeekly INH / RRT given by DOTWeekly INH / RRT given by DOT
Primary Outcome Measures
NameTimeMethod
Cumulative rate of culture-confirmed or clinically diagnosed TB disease in participants3 years
Secondary Outcome Measures
NameTimeMethod
Percentage of participants who complete the treatment regimenEnrollment up to Month 3 (3RPT/INH)
Percentage of participants with drug discontinuation for any reason and due to adverse drug reactions associated with 3RPT/INHup to 30 days after the last dose of study drug
Percentage of patients with Grade 3 or 4 drug toxicities and deaths associated with 3RPT/INHup to 30 days after the last dose of study drug
The proportion of rifampicin and/or isoniazid resistance of M. tuberculosis isolates in patients who develop TB in preventive treatment group.3 years
Measure the quantitative and qualitative changes of the results of QuantiFERON Gold In-Tube before and after preventive treatment.Enrollment up to 3 months after preventive treatment

Trial Locations

Locations (1)

Wenling No.1 People's Hospital, Zhejiang

🇨🇳

Taizhou, Zhejiang, China

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