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

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

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. To compare the risk of SDRs in 1HP treatment and in 3HP treatment

2. To explore side effect profile of 1HP

Methods:

This multicenter randomized control trial will compare the risk of SDRs under conventional 3HP regimen (Arm 1: 3HP), and a new regimen consisting of daily rifapentine (10 mg/kg) plus isoniazid (5 mg/kg) for 1 month (Arm 2: 1HP).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Taiwan University Hospital
• Treatments: Isoniazid; Rifapentine

Criteria

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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