Efficacy of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention

NCT02430259 | Completed Phase 3 DMC

• 1 other identifier: 81373064
• Study Type: interventional
• Target: 566
• Locations: 1 country
• Sites: 1

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.

Conditions

Silicosis; Tuberculosis

Keywords

rifapentine; isoniazid; QuantiFERON Gold In-Tube; tuberculin skin test

Outcome Measures

Primary Outcomes (1)

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

  3 years

Secondary Outcomes (5)

• 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

Study Arms (2)

Weekly Isoniazid / Rifapentine

EXPERIMENTAL

Weekly INH / RRT given by DOT

Drug: Weekly INH / RRT given by DOT

No preventive treatment

NO INTERVENTION

Follow up without intervention

Interventions

Weekly INH / RRT given by DOT DRUG

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

Weekly Isoniazid / Rifapentine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (1)

Wenling No.1 People's Hospital, Zhejiang

Taizhou, Zhejiang, 317500, China

Location

Related Publications (4)

• Xu H, Zhou J, Yang Q, Yang Y, Zhou F, Qian M, Lin X, Zhang W, Shao L, Ruan Q. QuantiFERON-TB supernatant-based biomarkers predicting active tuberculosis progression. Int J Infect Dis. 2025 Aug;157:107915. doi: 10.1016/j.ijid.2025.107915. Epub 2025 May 3.

  PMID: 40320069 DERIVED

• 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.

  PMID: 34042560 DERIVED

• 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.

  PMID: 32553881 DERIVED

• 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.

  PMID: 31770617 DERIVED

MeSH Terms

Conditions

Silicosis; Tuberculosis

Interventions

Isoniazid; rifapentine

Condition Hierarchy (Ancestors)

Pneumoconiosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lung Injury; Occupational Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Wenhong Zhang, MD,PhD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Division of Infectious Diseases

Study Record Dates

• First Submitted: April 16, 2015
• First Posted: April 30, 2015
• Study Start: March 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: June 30, 2020

Record last verified: 2020-06

Locations

CN (1)