Toward a Safe and Reachable Preventive Therapy for LTBI: a Multicenter Randomized Controlled Study in Taiwan

NCT02208427 | Unknown Phase 3 DMC

• 1 other identifier: 201309055MINC
• Study Type: interventional
• Target: 283
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Tuberculosis (TB) remains the most important infectious disease in the world. Keys to successful control of TB is rapid diagnosis, prompt treatment, as well as effective preventive therapy for contacts with latent TB infection (LTBI). Current methods for the diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA). For preventive therapy, the recommended regimens include daily isoniazid for 9 months and daily rifampicin for 4 months. By incorporating long-acting rifapentine, a new regimen combining weekly rifapentine and high-dose isoniazid for a total of 12 doses has been proven of equal potency and toxicity. However, the treatment completion rate is much higher in weekly treatment for 3 months than daily treatment for 9 months. It is reasonable that using rifapentine-based preventive therapy can markedly increase the completion rate. However, study is lacking, especially in Asia, the high endemic area of TB. With the effort of all health care workers and public health personnel, the incidence of TB in Taiwan has gradually declined in recent 10 years. In order to maintain the trend of decreasing in incidence, preventive therapy for LTBI become more and more important. However, which is the best preventive regimen for LTBI is still unknown. Therefore, we conduct the prospective randomized multicenter studies to compare the treatment completion rate of two regimens in Taiwan. The first regimen is daily isoniazid for 9 months. The second is weekly rifapentine plus high-dose isoniazid for 3 months.

Conditions

Latent Tuberculosis Infection

Keywords

isoniazid, LTBI, rifapentine, TST

Outcome Measures

Primary Outcomes (1)

• completion rate

  This prospective randomized interventional study is aimed to assess the completion rate of two different preventive regimens for LTBI by intent-to-treat analysis. Interruption of preventive therapy due to any reasons will be considered as incompletion.

  2 years

Secondary Outcomes (3)

• side effect

  3 months in the 3M_RH group and 9 months in the 9M_INH group

• interruption

  3 months in the 3M_RH group and 9 months in the 9M_INH group

• active TB

  2 years after enrollment

Study Arms (2)

3M_RH

EXPERIMENTAL

Rifapentine and Isoniazid for 3 months: weekly oral rifapentine 15 mg/kg plus isoniazid 15 mg/kg for 12 doses

Drug: Rifapentine and Isoniazid for 3 months

9M_INH

ACTIVE COMPARATOR

Isoniazid for 9 months: daily oral isoniazid 5 mg/kg for 9 months

Drug: Isoniazid for 9 months

Interventions

Rifapentine and Isoniazid for 3 months DRUG

weekly oral Rifapentine 15 mg/kg plus Isoniazid 15 mg/kg for 12 doses

Also known as: Priftin, Isoniazid

3M_RH

Isoniazid for 9 months DRUG

daily oral Isoniazid 5 mg/kg for 9 months under supervision (conventional IPT)

Also known as: Isoniazid

9M_INH

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Household contacts of TB or TB contacts in schools or densely-populated institutes
• Age ≥12 year-old
• Index case having smear-positive pulmonary TB
• Contact with index case for \>8 hours within single day or \>40 hours within total transmissible period
• TST ≥10 mm within one month
• Born in 1986 or after (not applicable in the National Taiwan University Hospital Hsin-Chu branch and Chang-Hua Hospital)

You may not qualify if:

• Clinical or radiographic evidence of active TB
• Index case having culture-negative pulmonary TB
• Index case having Isoniazid or Rifampin-resistant TB
• Receiving medications with significant interactions with Isoniazid, Rifampin, or Rifapentine
• Allergy to Isoniazid, Rifampin, or Rifapentine
• Sero-positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Documented liver cirrhosis
• Human immunodeficiency virus (HIV) infection
• Receiving immunosuppressants
• Receiving biological agents
• Hemoglobin \<8 g/dL
• Neutrophil \<750000 /mL
• Total bilirubin \>2.5 mg/dL
• Aspartic transaminase (AST) or alanine transaminase (ALT) \>2 folds of upper limit of normal (ULN)
• Pregnant or breast-feeding

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (1)

• Sun HY, Huang YW, Huang WC, Chang LY, Chan PC, Chuang YC, Ruan SY, Wang JY, Wang JT. Twelve-dose weekly rifapentine plus isoniazid for latent tuberculosis infection: A multicentre randomised controlled trial in Taiwan. Tuberculosis (Edinb). 2018 Jul;111:121-126. doi: 10.1016/j.tube.2018.05.013. Epub 2018 Jun 7.

  PMID: 30029896 DERIVED

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

rifapentine; Isoniazid

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jann-Yuan Wang, MD. PhD.

  National Taiwan University 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: SPONSOR

Study Record Dates

• First Submitted: July 31, 2014
• First Posted: August 5, 2014
• Study Start: August 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: December 15, 2016

Record last verified: 2016-12

Locations

TW (1)