Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as voriconazole (Vfend)
voriconazole · 9 trials · 9 indications
Number of deaths measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
Number of participants with proven (deep tissue infection, fungemia, or endemic fungal infections) or probable IFI (at least 1 host criterion \[fever, body temperature \<36 or \>38 degrees Celsius, graft-versus-host disease, use of corticosteroids\]; and 1 microbiological criterion \[fungal or yeasts\]; or clinical criteria \[abnormal site consistent with infection\]) as defined by European Organization for Research and Treatment of Cancer Mycosis Study Group (EORTC/MSG) criteria. Complete case analysis: must be evaluable until Day 28 or had developed a proven or probable IFI by the final visit.
AUC12,ss was obtained by the Linear/Log trapezoidal method.
AUC12,ss was obtained by the Linear/Log trapezoidal method.
AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method.
AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method.
Successful global outcome: composite assessment of radiological and mycological responses; defined as complete or partial radiological response and mycological eradication (absence of aspergillus); no success=criteria not met. Assessment was determined by the Data Review Committee (DRC). Complete response: resolution of radiographic and or bronchoscopic abnormalities attributable to aspergillosis present at baseline; partial response: reduction in diameter ≥ 50 percent on chest tomodensitometry (TDM) or regressed lesion on endoscopy witnessed by 2 different operators without any new lesion.
| Arm | Type | Description |
|---|---|---|
| Voriconazole | ACTIVE_COMPARATOR | Voriconazole monotherapy |
| Voriconazole and Anidulafungin | EXPERIMENTAL | Combination therapy with voriconazole and anidulafungin |
| Early treatment | EXPERIMENTAL | Voriconazole starts within 18 hours of onset of fever intravenously with a loading dose of 6 mg/kg q12h for the first two doses followed by 4 mg/kg q12h (maintenance dose). Switched to oral treatment (200 mg BID) is possible after at least four days. Treatment will be ended if the patient is afebrile (\< 38.0 °C) for 7 days with neutrophil counts \< 500/µL, or if the patient is afebrile (\< 38.0 °C) for 2 days with neutrophil counts \> 500/µL. |
| Deferred treatment | OTHER | Treatment with voriconazole (for dosage see "early treatment arm") is initiated only if a patient is persistently febrile on day 5 after the onset of fever despite antibiotic treatment. |
| 1.0 | EXPERIMENTAL | Immunocompromised children aged 2 to \<15 and 12 to \<15 years weighing \<50 kg who are at high risk for systemic fungal infection. |
| 2.0 | EXPERIMENTAL | Immunocompromised children aged 12 to \<15 years weighing more than 50 kg who are at high risk for systemic fungal infection. |
| Children aged 2 to <12 years | EXPERIMENTAL | Immunocompromised children aged 2 to \<12 years who are at high risk for systemic fungal infection. |
| 1 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| voriconazole | DRUG | First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV BID plus anidulafungin placebo IV qd. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin placebo IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin placebo IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. |
| anidulafungin | DRUG | First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin 100 mg IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. |
| voriconazole (Vfend) | DRUG | voriconazole, early treatment |
Inclusion Criteria: * Immunocompromised state due to either 1. receipt of hematopoeitic stem cell transplantation or 2. hematologic malignancy; * Diagnosis of possible, probable, or proven invasive aspergillosis. Exclusion Criteria: * Patients with aspergilloma or chronic aspergillosis * Receipt ...