Table 3.
Safety and Premature Discontinuation of Assigned Regimen.*
| Variable | Control (N = 825) | Rifapentine–Moxifloxacin (N = 846) | Rifapentine (N = 835) | Total (N = 2506) |
|---|---|---|---|---|
| Primary safety outcome | ||||
| Grade 3 or higher adverse event — no. (%) | 159 (19.3) | 159 (18.8) | 119 (14.3) | 437 (17.4) |
| Percentage-point difference from control (95% CI)† | NA | −0.6 (−4.3 to 3.2) | −5.1 (−8.7 to −1.5) | NA |
| Secondary safety outcome | ||||
| Treatment-related grade 3 or higher adverse event — no. (%) | 81 (9.8) | 109 (12.9) | 64 (7.7) | 254 (10.1) |
| Percentage-point difference from control (95% CI)† | NA | 3.0 (−0.0 to 6.1) | −2.2 (−4.9 to 0.6) | NA |
| Other safety outcomes | ||||
| Any serious adverse event — no. (%) | 56 (6.8) | 37 (4.4) | 39 (4.7) | 132 (5.3) |
| Death — no. (%)‡ | 7 (0.8) | 3 (0.4) | 4 (0.5) | 14 (0.6) |
| Any adverse event resulting in discontinuation of assigned treatment — no. (%)§ | 7 (0.8) | 16 (1.9) | 11 (1.3) | 34 (1.4) |
| Any grade 3 or higher adverse event within 28 weeks after randomization | 159 (19.3) | 194 (22.9) | 138 (16.5) | 491 (19.6) |
| ALT or AST level ≥5×ULN — no. (%)¶ | 24 (2.9) | 16 (1.9) | 13 (1.6) | 53 (2.1) |
| ALT or AST level ≥10×ULN — no. (%) | 9 (1.1) | 4 (0.5) | 5 (0.6) | 18 (0.7) |
| Serum total bilirubin level ≥3×ULN — no. (%)‖ | 8 (1.0) | 28 (3.3) | 20 (2.4) | 56 (2.2) |
| Hy’s law criteria of ALT or AST level ≥3×ULN plus serum total bilirubin level ≥2×ULN — no. (%) | 7 (0.8) | 10 (1.2) | 8 (1.0) | 25 (1.0) |
| Premature discontinuation of assigned regimen in the microbiologically eligible population | ||||
| Discontinuation of assigned regimen for any reason — no./total no. (%) | 61/768 (7.9) | 55/791 (7.0) | 37/784 (4.7) | 153/2343 (6.5) |
| Percentage-point difference from control (95% CI)† | NA | −1.0 (−3.6 to 1.6) | −3.3 (−5.7 to −0.9) | NA |
The safety analysis population included all the participants who had undergone randomization and received at least one dose of the assigned treatment. Safety was assessed during the on-treatment period (the time during which the participants were receiving the trial medications and up to 14 days after the last dose), unless otherwise specified. Adverse events were graded by the site investigators according to the National Cancer Institute Common Terminology Criteria for Adverse Events.31 ALT denotes alanine aminotransferase, AST aspartate aminotransferase, and ULN upper limit of the normal range.
The analysis was adjusted for the stratification factors of presence of cavitation on baseline chest radiography at baseline and HIV status.
In the control group, death was due to paracoccidioides infection, sepsis, papillary thyroid cancer, central nervous system lesion, hemoptysis, or pulmonary embolism (in 1 participant each), and there was one unexplained death. In the rifapentine–moxifloxacin group, death was due to thrombotic thrombocytopenic purpura, congestive cardiac failure, or pulmonary tuberculosis (in 1 participant each). In the rifapentine group, death was due to alcohol poisoning, road traffic accident, or pulmonary embolism (in 1 participant each), and there was one unexplained death.
The assigned treatment was discontinued because of hepatitis (in 6 participants) or seizure (in 1 participant) in the control group; because of hepatitis (in 11 participants) or thrombocytopenia, QT prolongation, tendonitis, pruritus, or maculopapular rash (in 1 participant each) in the rifapentine–moxifloxacin group; and because of hepatitis (in 8 participants) or neutropenia, bacterial pneumonia, or drug reaction with eosinophilia and systemic symptoms (in 1 participant each) in the rifapentine group.
An ALT or AST level of at least 5×ULN corresponds with an adverse event of grade 3 or higher.
A total bilirubin level of at least 3×ULN corresponds with an adverse event of grade 3 or higher.