Rifampin in latent TB
Trial question
Is 4-month regimen of rifampin noninferior to 9-month regimen of isoniazid for the prevention of active tuberculosis in adults with latent tuberculosis infection?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
59.0% female
41.0% male
N = 6012
6012 patients (3552 female, 2460 male).
Inclusion criteria: adult patients with latent tuberculosis infection.
Key exclusion criteria: exposure to a patient with active tuberculosis whose isolates were resistant to either trial drug, current or planned pregnancy, use of medications with potentially serious interactions with either trial drug, history of allergy to either trial drug, or current active tuberculosis.
Interventions
N=3023 rifampin (oral dose of 10 mg/kg body weight, maximum dose of 600 mg, taken daily for 4 months).
N=2989 isoniazid (oral dose of 5 mg/kg of body weight, maximum dose of 300 mg, taken daily for 9 months).
Primary outcome
Incidence of confirmed active tuberculosis
0.05
0.05
0.1/100 py
0.0/100 py
0.0/100 py
0.0/100 py
0.0/100 py
Rifampin
Isoniazid
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in the incidence of confirmed active tuberculosis (0.05/100 py vs. 0.05/100 py).
Secondary outcomes
No significant difference in the incidence of confirmed or clinically diagnosed active tuberculosis (0.1/100 py vs. 0.11/100 py).
Safety outcomes
No significant difference in trial drug discontinued due to death.
Significant differences in adverse events (2.8% vs. 5.8%), discontinuation of trial drug due to grade 3-5 adverse events (0.8% vs. 2.1%) and grade 3-4 hepatotoxic events (0.3% vs. 1.7%).
Conclusion
In adult patients with latent tuberculosis infection, rifampin was noninferior to isoniazid with respect to the incidence of confirmed active tuberculosis.
Reference
Menzies D, Adjobimey M, Ruslami R et al. Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults. N Engl J Med. 2018 Aug 2;379(5):440-453.
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