Efficacy of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention

June 27, 2020 updated by: Wen-hong Zhang, Huashan Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

566

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Zhejiang
      • Taizhou, Zhejiang, China, 317500
        • Wenling No.1 People's Hospital, Zhejiang

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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
  • I
  • RPT
  • rifapentine
  • 3 RPT/INH
No Intervention: No preventive treatment
Follow up without intervention

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of participants with drug discontinuation for any reason and due to adverse drug reactions associated with 3RPT/INH
Time Frame: up to 30 days after the last dose of study drug
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
Time Frame: up to 30 days after the last dose of study drug
up to 30 days after the last dose of study drug
Percentage of participants who complete the treatment regimen
Time Frame: Enrollment up to Month 3 (3RPT/INH)
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.
Time Frame: 3 years
3 years
Measure the quantitative and qualitative changes of the results of QuantiFERON Gold In-Tube before and after preventive treatment.
Time Frame: Enrollment up to 3 months after preventive treatment
Enrollment up to 3 months after preventive treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Huashan Hospital

Investigators

  • Principal Investigator: Wenhong Zhang, MD,PhD, Huashan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Actual)

June 1, 2018

Study Completion (Actual)

June 1, 2018

Study Registration Dates

First Submitted

April 16, 2015

First Submitted That Met QC Criteria

April 25, 2015

First Posted (Estimate)

April 30, 2015

Study Record Updates

Last Update Posted (Actual)

June 30, 2020

Last Update Submitted That Met QC Criteria

June 27, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 81373064

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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