Efficacy of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention

Sponsor

Huashan Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02430259

Collaborator

(none)

566

Enrollment

Location

Arms

Duration (Months)

14.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Silicosis Tuberculosis	Drug: Weekly INH / RRT given by DOT	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

566 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for 3 Months for Tuberculosis Preventive Treatment: A Randomized Controlled Study in China

Study Start Date :

Mar 1, 2015

Actual Primary Completion Date :

Jun 1, 2018

Actual Study Completion Date :

Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Weekly Isoniazid / Rifapentine Weekly INH / RRT given by DOT	Drug: Weekly INH / RRT given by DOT weekly oral Rifapentine 15 mg/kg (up to 900mg) plus Isoniazid 15 mg/kg (up to 900mg) for 12 doses Other Names: isoniazid I INH rifapentine RPT 3 RPT/INH
No Intervention: No preventive treatment Follow up without intervention

Arm

Intervention/Treatment

Experimental: Weekly Isoniazid / Rifapentine

Weekly INH / RRT given by DOT

Drug: Weekly INH / RRT given by DOT

weekly oral Rifapentine 15 mg/kg (up to 900mg) plus Isoniazid 15 mg/kg (up to 900mg) for 12 doses

Other Names:

isoniazid

INH

rifapentine

RPT

3 RPT/INH

No Intervention: No preventive treatment

Follow up without intervention

Outcome Measures

Primary Outcome Measures

Cumulative rate of culture-confirmed or clinically diagnosed TB disease in participants [3 years]

Secondary Outcome Measures

Percentage of participants with drug discontinuation for any reason and due to adverse drug reactions associated with 3RPT/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 3RPT/INH [up to 30 days after the last dose of study drug]
Percentage of participants who complete the treatment regimen [Enrollment up to Month 3 (3RPT/INH)]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.