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CompletedNCT02430259Updated Jun 30, 2020

Efficacy of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention

A Phase 3 interventional study of Weekly INH / RRT given by DOT in Silicosis and Tuberculosis, sponsored by Huashan Hospital. Completed at 1 site in China. Open to male participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2020-06-30.

Sponsored by Huashan Hospital · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
566
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
Male
01

Study 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.

Read the 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.

02

Conditions studied

  • Silicosis
  • Tuberculosis

Keywords

  • rifapentine
  • isoniazid
  • QuantiFERON Gold In-Tube
  • tuberculin skin test
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
Male
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
566 participants (estimated)

Study arms

  • Experimental
    Weekly Isoniazid / Rifapentine

    Weekly INH / RRT given by DOT

    Drug: Weekly INH / RRT given by DOT

  • No intervention
    No preventive treatment

    Follow up without intervention

Interventions

  • DrugWeekly 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

    Also known as: isoniazid, I, INH, rifapentine, RPT, 3 RPT/INH

05

What researchers measure

Primary outcomes

  1. Cumulative rate of culture-confirmed or clinically diagnosed TB disease in participants

    Time frame: 3 years

Secondary outcomes

  1. 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

  2. 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

  3. Percentage of participants who complete the treatment regimen

    Time frame: Enrollment up to Month 3 (3RPT/INH)

  4. 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

  5. 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

06

Study locations

1 site
  • Wenling No.1 People's Hospital, Zhejiang
    Taizhou, Zhejiang 317500, China
07

References and documents

Publications

  • Ruan QL, Yang QL, Gao YX, Wu J, Lin SR, Zhou JY, Shao LY, Wang S, Liu QQ, Gao Y, Jiang N, Zhang WH. Transcriptional signatures of human peripheral blood mononuclear cells can identify the risk of tuberculosis progression from latent infection among individuals with silicosis. Emerg Microbes Infect. 2021 Dec;10(1):1536-1544. doi: 10.1080/22221751.2021.1915184. PubMed 34042560 ↗
  • Ruan QL, Huang XT, Yang QL, Liu XF, Wu J, Pan KC, Shen YJ, Cai LM, Ling Q, Jiang T, Hong JJ, Wang XD, Ma CL, Peng GQ, Wang XZ, Mao JC, Wu TZ, Lin MY, Shao LY, Zhang WH. Efficacy and safety of weekly rifapentine and isoniazid for tuberculosis prevention in Chinese silicosis patients: a randomized controlled trial. Clin Microbiol Infect. 2021 Apr;27(4):576-582. doi: 10.1016/j.cmi.2020.06.008. Epub 2020 Jun 15. PubMed 32553881 ↗
  • Yang Q, Ruan Q, Liu X, Shen Y, Jiang T, Wu J, Cai L, Pan K, Lin M, Huang X, Shao L, Zhang W. Preventive tuberculosis treatment effect on QuantiFERON TB-Gold in-tube testing in a high tuberculosis-endemic country: A clinical trial. Int J Infect Dis. 2020 Feb;91:182-187. doi: 10.1016/j.ijid.2019.11.023. Epub 2019 Nov 23. PubMed 31770617 ↗
08

Registry details

Key details

Study ID
NCT02430259
Lead sponsor
Huashan Hospital
Responsible party
Wen-hong Zhang (Director of Division of Infectious Diseases, Huashan Hospital) — Principal investigator
First posted
Apr 30, 2015
Start date
Mar 2015
Primary completion
Jun 2018
Completion
Jun 2018
Last update
Jun 30, 2020

Study contacts

Wenhong Zhang, MD,PhD
principal investigator · Huashan Hospital

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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