Table 2.
Severity Scale Threshold and Definition for Clinically Relevant Adverse Events of Special Interest in the endTB Observational Study
| Adverse Events of Special Interest | Threshold Grade for Clinically Relevant Adverse Events of Special Interest and Definitions | |
|---|---|---|
| Grade(s) | Definition(s), by Grade | |
| QT prolongation | ≥3 | Grade 3, QTcF ≥501 msec, no symptoms Grade 4, QTcF ≥501 or 60 msec increase and symptomsa |
| Peripheral neuropathy | All grades | Impairment or discomfort/BPNS subjective sensory neuropathy score: Grade 1, mild/BPNS 1–3 on any side Grade 2, moderate/BPNS 4–6 Grade 3, severe/BPNS 7–10 Grade 4, sensory loss, incapacitating |
| Optic neuritis | All grades | Grade 1, clinical diagnosis, no symptoms ≥Grade 2, limiting vision (20/40 or worse) |
| Myelosuppression | Anemia ≥3 | Grade 3, haemoglobin <7.9 g/dL |
| Thrombocytopenia ≥3 | Grade 3, platelets decreased <50 000/mm3 | |
| Leukopenia ≥3 | Grade 3, white blood cell decrease <2000/mm3 | |
| Lymphocytopenia ≥3 | Grade 3, lymphocyte decrease <500/mm3 | |
| Neutropenia ≥2 | Grade 2, absolute neutrophil count <750/mm3 | |
| Pancytopenia ≥2 | Grade 2, any combination of the above | |
| Hearing loss | All grades | Grade 1, threshold shift of ≥15–25 dB at ≥2 frequencies; for patients with no baseline, an adverse event was declared if abnormal hearing was identified during treatment |
| Acute renal failure | ≥2 | Grade 2, creatinine, ≥2–3 times above baseline or, in absence of
baseline, 1.6–3 times above the upper limit of normal creatinine Grade 2, creatinine clearance, <90–60 mL/min or 10%– <30% decrease from baseline |
| Electrolyte depletion | All grades | Grade 1, potassium <3.4 mmol/L requiring potassium
replacement Grade 1, magnesium <0.7 mmol/L requiring magnesium replacement |
| Hepatotoxicity | ≥3 | Grade 3, alanine aminotransferase and/or aspartate aminotransferase >5 times the upper limit of normal |
| Hypothyroidism | ≥2 | Grade 2, symptomatic requiring thyroxin replacement |
Abbreviations: BPNS, brief peripheral neuropathy screen; QT, QTcF, corrected QT interval by Fredericia formula.
Symptoms include 1 of the following: Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia.