Short Course Rifapentine and Isoniazid for the Preventive Treatment of Tuberculosis(SCRIPT-TB) (TB)

Tuberculosis (TB) remains the most important infectious disease in the world. Preventive treatment plays an important role in successful control of TB. The investigators' previous study showed a 3-month weekly rifapentine and isoniazid regimen had a high protective efficacy but an unsatisfactory completion rate. Therefore, the investigators suppose that a one-month (12-dose) regimen of rifapentine and isoniazid (1RPT/INH) to be equivalent to a 3-month weekly rifapentine and isoniazid regimen with similar efficacy and higher completion rate. Relevant study is lacking in China where the TB burden is high with the incidence rate of 70/100, 000.

Silicosis is a risk factor of Mycobacterium tuberculosis infection. This is an open-label, non-randomized clinical trial to evaluate the efficacy and safety of the 1RPT/INH to prevent tuberculosis (TB) compared with those who do not receive preventive treatment among silicotic patients.

Study Overview

• Status: Unknown
• Conditions: Silicosis Tuberculosis
• Intervention / Treatment: Drug: Isoniazid；Rifapentine

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, alternative shortened courses such as 1-month daily rifapentine and isoniazid have been evaluated in HIV-infected individuals for its non-inferiority, safety and convenience compared with traditional monotherapy. And the treatment completion rate is higher. The investigators' previous study showed a 3-month weekly rifapentine and isoniazid regimen had a high protective efficacy but an unsatisfactory completion rate. Therefore, the investigators suppose that a one-month (12-dose) regimen of rifapentine and isoniazid (1RPT/INH) to be equivalent to a 3-month weekly rifapentine and isoniazid regimen with similar efficacy and higher completion rate. Relevant study is lacking in China where the TB burden is high with the incidence rate of 70/100, 000.

Silicosis is a risk factor of Mycobacterium tuberculosis infection. This is an open-label, non-randomized clinical trial to evaluate the efficacy and safety of the 1RPT/INH to prevent tuberculosis (TB) compared with those who do not receive preventive treatment among silicotic patients.

• Study Type: Interventional
• Enrollment (Anticipated): 566
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Taizhou, Zhejiang, China, 317500
      • Recruiting
      • Wenling No.1 People's Hospital, Zhejiang
      • Contact: Miaoyao Ling, MD; Phone Number: +86576-89668099; Email: lmy120904@sina.com
      • Sub-Investigator: Xitian Huang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isoniazid/ Rifapentine 3 times a week; Intervention：Isoniazid/ Rifapentine 3 times a week given by DOT oral Rifapentine (450mg) plus Isoniazid (400mg) for 12 doses	Drug: Isoniazid；Rifapentine; 1 months (12 doses) of three-weekly rifapentine at a dose of 450mg plus isoniazid at a dose of 400mg given under direct observation; Other Names: Isoniazid I INH; Rifapentine RPT; 1RPT/INH 1HP
No Intervention: No Intervention; No preventive treatment Follow up without intervention. Have already done.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with drug discontinuation for any reason and due to adverse drug reactions associated with 1RPT/INH	Percentage of participants with drug discontinuation for any reason and due to adverse drug reactions associated with 1RPT/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 1RPT/INH	Percentage of patients with Grade 3 or 4 drug toxicities and deaths associated with 1RPT/INH	up to 30 days after the last dose of study drug
Percentage of participants who complete the treatment regimen	Percentage of participants who complete the treatment regimen	Enrollment up to Month 1 (1RPT/INH)

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Wenling No.1 People's Hospital, China
• Investigators: Principal Investigator: Wenhong Zhang, MD，PhD, Huashan Hospital of Fudan University，Shanghai，China

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: April 1, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): April 5, 2019
• Last Update Submitted That Met QC Criteria: April 3, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: rifapentine; isoniazid; preventive
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Occupational Diseases; Actinomycetales Infections; Mycobacterium Infections; Pneumoconiosis; Lung Diseases, Interstitial; Lung Injury; Tuberculosis; Silicosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Fatty Acid Synthesis Inhibitors; Rifapentine; Rifampin; Isoniazid
• Other Study ID Numbers: 2017ZX10201302-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No