Risk of SDRs Under 3HP and 1HP Regimen for LTBI

NCT04094012 | Completed Phase 3

• 1 other identifier: 201812127MINB
• Study Type: interventional
• Target: 490
• Locations: 1 country
• Sites: 1

Brief Summary

Successful implement of preventive therapy for subjects with latent tuberculosis infection (LTBI) is the critical step for elimination of tuberculosis (TB). The major obstacle of traditional preventive therapy is the unacceptable long treatment duration, taking isoniazid 5mg/kg daily for a total of 9 months (9H), thus seriously compromising its acceptability. With the introduction of 12-doses weekly high-dose (15 mg/kg) rifapentine plus isoniazid (3HP regimen), the completion rate of 3HP has be shown to be much higher than 9H. However, 4.9% to 9.1% of LTBI cases who received 3HP failed to complete treatment because of side effects. Systemic drug reactions (SDRs), even hypotension and shock, under 3HP treatment are higher than 9H treatment. A recent study in HIV patients demonstrated that a new short-term regimen, consisting of isoniazid 5mg/kg plus rifapentine 10mg/kg daily for one month (1HP), has a similar risk of adverse reactions as 3HP. Clinical study with head-to-head comparison between 3HP and 1HP, however, remains lacking. The prospective multicenter study is conducted to investigate whether risk of SDRs under 1HP is lower than that under 3HP. Hypothesis: 1HP has a lower incidence rate of SDRs than 3HP Objectives:

1. 1.To compare the risk of SDRs in 1HP treatment and in 3HP treatment
2. 2.To explore side effect profile of 1HP

Conditions

Latent Tuberculosis Infection

Keywords

isoniazid; latent tuberculosis infection; preventive therapy; rifapentine; systemic drug reaction; therapeutic drug monitoring

Outcome Measures

Primary Outcomes (1)

• number of participants with systemic drug reactions

  AEs that met either of the following: (1) hypotension (systolic blood pressure \<90 mm Hg), urticaria, angioedema, acute bronchospasm, or conjunctivitis; and (2) \>4 of the following symptoms occurring concurrently (\>1 of which had to be grade 2 or higher): weakness, fatigue, nausea, vomiting, headache, fever, aches, sweats, dizziness, shortness of breath, flushing, or chills.

  within 3 months after starting preventive therapy

Secondary Outcomes (5)

• number of participants with any flu-like symptoms

  within 3 months after starting preventive therapy

• number of participants with hepatotoxicity

  within 3 months after starting preventive therapy

• Treatment completion rate

  within 3 months after starting preventive therapy

• Plasma level of isoniazid, rifapentine, acetyl-isoniazid, and Desacetyl-rifapentine

  within 3 months after starting preventive therapy

• Characteristics associated with the development of systemic drug reactions

  within 3 months after starting preventive therapy

Study Arms (2)

3-months weekly RPT plus INH (3HP)

ACTIVE COMPARATOR

weekly RPT (900 mg for participants with body weight \>50.0 kg; 750 mg for 32.1-50.0 kg; 600 mg for 25.1-32.0 kg; and 450 mg for 14.1-25.0 kg) plus INH (dose: 15 mg/kg, rounded up to nearest 150 mg; maximum 900 mg) for a total of 12 doses.

Drug: isoniazid and rifapentine

1-month daily RPT plus INH (1HP)

EXPERIMENTAL

daily RPT (dose: 600 mg for participants with body weight ≥45.0 kg; 450 mg for \<45.0 kg) plus INH (dose: 300 mg) for a total of 28 days.

Drug: isoniazid and rifapentine

Interventions

isoniazid and rifapentine DRUG

This prospective multicenter randomized control trial (RCT) will be conducted on LTBI cases (see 2. Study population) to compare the risk of SDRs under conventional 3HP regimen (Arm 1: 3HP) and a new regimen consisting of daily RPT (10 mg/kg) plus INH (5 mg/kg) for 1 month (Arm 2: 1HP)

Also known as: INH/RPT

1-month daily RPT plus INH (1HP); 3-months weekly RPT plus INH (3HP)

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:

• aged ≥12 years
• close contact (defined as unprotected exposure of ≥8 hours in a single day or a cumulative duration of ≥40 hours, as per the national policy of Taiwan) with patients diagnosed with acid-fast smear (AFS)-positive pulmonary TB
• diagnosed with LTBI using either a tuberculin skin test (TST) or QuantiFERON-TB Gold in-tube assay (QFT; Cellestis/Qiagen, Carnegie, Australia)

You may not qualify if:

• suspected to have active pulmonary TB because of their clinical symptoms or chest radiography findings
• concurrently using drugs with severe drug-drug interactions
• allergic to INH, rifampin, or RPT
• a life expectancy \<3 years

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Related Publications (1)

• Huang HL, Lee MR, Lee CH, Cheng MH, Lu PL, Sheu CC, Wang JY, Chong IW, Yang JM. One-month daily and three-month weekly rifapentine plus isoniazid are comparable in completion rate and safety for latent tuberculosis infection in non-HIV Population: a randomized controlled trial. Clin Microbiol Infect. 2024 Nov;30(11):1410-1417. doi: 10.1016/j.cmi.2024.06.024. Epub 2024 Jul 10.

  PMID: 38996972 DERIVED

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

Isoniazid; rifapentine

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: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: September 18, 2019
• Study Start: September 24, 2019
• Primary Completion: October 8, 2023
• Study Completion: December 15, 2023
• Last Updated: December 26, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)