A Study of the Safety and Efficacy of Posaconazole Versus Voriconazole for the Treatment of Invasive Aspergillosis (MK-5592-069)
Condition: Fungal Infections; Invasive Pulmonary Aspergillosis
MeSH terms: Mycoses; Aspergillosis; Pulmonary Aspergillosis; Invasive Pulmonary Aspergillosis
Intervention: Posaconazole; Voriconazole; Placebo
Intervention description: POS IV: Day 1: 300 mg BID Day 2-84: 300 mg QD POS oral: Day 1: 300 mg BID Day 2-84: 300 mg QD; VOR IV: Day 1: 6 mg/kg per body weight administered BID Day 2-84: 4 mg/kg per body weight administered BID VOR oral: Day 1: 300 mg BID Day 2-84: 200 mg BID; Matching placebo received for Posaconazole (IV and oral) or Voriconazole (oral)
Intervention MeSH terms: Voriconazole; Posaconazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 585.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety and efficacy of posaconazole (POS) versus
      voriconazole (VOR) in the treatment of adults and adolescents with invasive aspergillosis
      (IA). The primary hypothesis is that the all-cause mortality through Day 42 in the POS
      treatment group is non-inferior to that in the VOR treatment group.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Weight >40 kg (88 lb) and ≤150 kg (330 lb); if between 13 and 14 years of age must
             weigh >= 50 kg (110 lb)

          -  Must meet the criteria for proven, probable, or possible IA as per 2008 European
             Organization for Research and Treatment of Cancer/Invasive Fungal Infections
             Cooperative Group and the National Institute of Allergy and Infectious Diseases
             Mycoses Study Group (EORTC/MSG) disease definitions at the time of randomization.
             Proven IA will include those participants with the demonstration of fungal elements
             (by cytology, microscopy, or culture) in diseased tissue (sterile sampling). Probable
             IA includes participants with at least 1 host factor, clinical criteria, as well as
             mycological criteria including both direct and indirect methods. Possible IA includes
             participants with at least 1 host factor and clinical criteria but without mycological
             criteria. A modification to the 2008 EORTC/MSG criteria regarding risk factors has
             been made to allow for the inclusion of participants with any duration of neutropenia
             as an acceptable inclusion host factor.

          -  If with possible IA at time of randomization must be willing or be in process of an
             ongoing diagnostic work up which is anticipated to result in a mycological diagnosis
             of proven or probable IA postrandomization.

          -  Must have a central line (e.g., central venous catheter, peripherally-inserted central
             catheter, etc.) in place or planned to be in place prior to beginning IV study
             therapy. If without central catheter access, must be clinically stable and able to
             receive oral study therapy.

          -  Acute IA defined as duration of clinical syndrome of <30 days.

          -  Must be willing to adhere to dosing, study visit schedule, and mandatory procedures as
             outlined in the protocol. The participant must be willing to continue on study therapy
             for up to 12 weeks and remain in the study through the 1-month follow-up visit.

          -  The participant must have the ability to transition to oral study therapy during the
             course of the study.

          -  Female participants of child-bearing potential must be using a medically accepted
             method of birth control before beginning study-drug treatment and agree to continue
             its use for 30 days after stopping study medication

          -  Is not taking prohibited antifungal prophylaxis or treatment

        Exclusion Criteria:

          -  Chronic (>1 month duration) IA, relapsed/recurrent IA, or refractory IA which has not
             responded to antifungal therapy.

          -  Has pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis
             (ABPA).

          -  Known mixed invasive mold fungal infection including Zygomycetes, and/or a known
             invasive Aspergillus fungal infection in which either study drug may not be considered
             active.

          -  Receipt of any systemic (oral, intravenous, or inhaled) antifungal therapy for this
             infection episode for 4 or more consecutive days (>= 96 hours) immediately before
             randomization.

          -  Developed the current episode of IA infection during receipt of >13 days of antifungal
             prophylaxis with an agent considered to be a mold-active antifungal agent.

          -  Receipt of posaconazole or voriconazole as empirical treatment for this infection for
             4 days (96 hours) or more within the 15 days immediately before randomization.

          -  Has condition that, in the opinion of the investigator, may interfere with optimal
             participation in the study.

          -  Known hypersensitivity or other serious adverse reaction to any azole antifungal
             therapy or to any other ingredient of the study medication used.

          -  Females who are pregnant, intend to become pregnant, or are nursing at the time of
             randomization.

          -  Known history of Torsade de Pointes, unstable cardiac arrhythmia or proarrhythmic
             conditions, or a history of recent myocardial infarction within 90 days of study
             entry.

          -  Has significant liver dysfunction

          -  Hepatic cirrhosis or a Child-Pugh score of C (severe hepatic impairment) at the time
             of randomization.

          -  Severe renal insufficiency (estimated creatinine clearance <20 mL/min) or on
             hemodialysis at the time of randomization or likely to require dialysis during the
             study.

          -  Known hereditary problem of galactose intolerance, Lapp lactase deficiency, or
             glucose-galactose malabsorption.

          -  Acute symptomatic pancreatitis within 6 months of study entry or a diagnosis of
             chronic pancreatitis at the time of randomization.

          -  Active skin lesion consistent with squamous cell carcinoma at the time of
             randomization, or a current or prior history of malignant melanoma within 5 years of
             study entry.

          -  On artificial ventilation or receiving acute Continuous Positive Airway Pressure
             (CPAP)/Bilevel Positive Airway Pressure (BPAP) at the time of randomization.

          -  Known or suspected Gilbert's disease at the time of randomization.

          -  Requires treatment with other medications that cannot be stopped and for which there
             is a known contraindication to co-administration of one or more of the study drugs.