Anidulafungin Plus Voriconazole Versus Voriconazole For The Treatment Of Invasive Aspergillosis

• Global Response at Week 6 [ Time Frame: Baseline, Day 42 (Week 6) ] [ Designated as safety issue: No ]
  Number of participants with a successful response (complete or partial global response). Complete response = resolution of all clinical signs and symptoms and >90% of lesions due to IA that were visible on radiologic studies at baseline (BL); partial response = clinical improvement and >50% improvement in radiological findings present at BL.
• All-cause Mortality at Week 6 in Participants With Possible, Probable, or Proven Invasive Aspergillosis (IA) [ Time Frame: Day 1 to Day 42 (Week 6) ] [ Designated as safety issue: Yes ]
  Number of deaths due to any cause measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
• All-cause Mortality at Week 12 in Participants With Probable or Proven Invasive Aspergillosis (IA) [ Time Frame: Day 1 to Day 84 (Week 12) ] [ Designated as safety issue: Yes ]
  Number of deaths due to any cause measured 12 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
• Mortality Due to Invasive Aspergillosis (IA) at Week 6 in Participants With Probable or Proven IA [ Time Frame: Day 1 to Day 42 (Week 6) ] [ Designated as safety issue: Yes ]
  Number of deaths due to Invasive Aspergillosis measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
• Time to Death: All-Cause Mortality [ Time Frame: Day 1 to Day 84 (Week 12) ] [ Designated as safety issue: Yes ]
  Survival time from start of treatment. Time to death defined as date of death due to any cause minus first treatment date + 1.
• Time to Death Due to Invasive Aspergillosis (IA) [ Time Frame: Day 1 to Day 84 (Week 12) ] [ Designated as safety issue: Yes ]
  Survival time from start of treatment. Time to death defined as date of death due to IA minus first treatment date + 1.

• Rate of global response at 6 weeks
• All cause mortality at 12 weeks
• Time to death (all cause mortality)

This study compares the effectiveness and safety of the combination of anidulafungin and voriconazole compared to that of voriconazole alone (which is generally considered the standard of care) for the treatment of Invasive Aspergillosis.

• Drug: voriconazole

  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.

  Other Name: Vfend
• Drug: anidulafungin

  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.

  Other Name: Eraxis
• Drug: voriconazole

  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.

  Other Name: Vfend

• Active Comparator: Voriconazole
  Voriconazole monotherapy
  Intervention: Drug: voriconazole
• Experimental: Voriconazole and Anidulafungin
  Combination therapy with voriconazole and anidulafungin
  Interventions:

  • Drug: anidulafungin
  • Drug: voriconazole

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 of 4 or more days of systemic antifungal treatment for the current episode of invasive aspergillosis
• Anticipated survival of less than 5 days or Karnofsky score <=20