Clinical trial NCT00811928: Safety and Efficacy Study of Posaconazole vs. Fluconazole for Prevention of Invasive Fungal Infection (P05387 AM1)(COMPLETED)
Official title: A Randomized, Open Label Parallel Controlled, Multicenter Study to Evaluate Safety and Efficacy of Posaconazole Oral Suspension Vs. Fluconazole (Capsule) in High-risk Leukopenic Patients for Prevention of Invasive Fungal Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukopenia
Keywords: high-risk leukopenic patients
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-12-19
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: A randomized, open label parallel controlled, multicenter study to evaluate safety and efficacy of Posaconazole oral suspension vs Fluconazole (capsule) in high-risk leukopenic patients for prevention of invasive fungal infection


Eligibility criteria: Inclusion Criteria:

* Participants must be 18-70 years of age of either sex
* Persistent neutropenia (Absolute Neutrophil Count \[ANC\] \< 500/mm\^3 \[0.5x10\^9/L\]）or probable neutropenia in 3-5 days is anticipated. Neutropenia \>= 7 days caused by the following reasons

  * Standard or dose-intense chemotherapy, anthracyclines or other acceptable chemotherapies ( any investigational drug is not permitted) for Acute Myelogenous Leukemia (AML) treatment
  * Retreatment of chemotherapy in case of AML recurrence
  * Myelodysplastic syndrome (MDS) shifts to AML and bone marrow arrest induction chemotherapy is required (not including acute phase of chronic myelogenous leukemia \[CML\])
* Informed consent obtained from participant or legal guardian

Exclusion Criteria:

* Participants previously treated with amphotericin B (AMB), fluconazole (FLZ), or itraconazole (ITZ) within 30 days of enrollment.
* Participants who have taken the following drugs:

  * terfenadine, cisapride, and ebastine within 24 hours before entry
  * astemizole at entry or within 10 days before entry
  * cimetidine, rifampin, carbamazepine, phenytoin, rifabutin, barbiturates, isoniazid atharanthine and anthracyclines within 24 hours before entry
* The above drugs are refrained during the investigation
* Serious organ diseases except hematological disorder such as cardiac or neurologic disorders or impairment expected to be unstable or progressive during the course of this study (eg, seizures or demyelinating syndromes, acute myocardial infarction within 3 months of study entry, myocardial ischemia, congestive heart failure, atrial fibrillation with ventricular rate \<60/min, or history of torsades de pointes, symptomatic ventricular or sustained arrhythmias), unstable electrolyte abnormalities.
* Participants who have used any investigational drugs or biologic agents other than their chemotherapy regimens within 30 days of study entry.
* Prior enrollment in this study.
* Participants with known or suspected hypersensitivity or idiosyncratic reaction to azole agents or amphotericin B.
* Participants with known or suspected invasive fungal infection (IFI) at screen
* Participants with severe renal insufficiency (estimated creatinine clearance less than 50 mL/minute or likely to require dialysis during the study), Alanine transaminase (ALT), Aspartate transaminase (AST), alkaline phosphatase or total bilirubin are \>2× (Upper Limit of Normal) ULN.
* Participants having an electrocardiogram (ECG) with a prolonged QTc interval: QTc greater than 450 msec for men and greater than 470 msec for women.
* Participants with AML or CML history.
* Participants with a history of allogeneic hematopoietic stem cell, bone marrow transplantation, autologous stem cell transplantation history.
* Female participants who are pregnant or are nursing.
* Alcohol and/or drug abuse.
* Participants cannot be compliant in the opinion of the investigator.

Primary outcomes:
measure: Number of Participants With Proven or Probable Diagnosis of Invasive Fungal Infection (IFI) During the Treatment Period
timeFrame: Up to 12 Weeks (84 days) plus 7 days
Secondary outcomes:
measure: Number of Participants With Proven or Probable Diagnosis of IFI Within 100 Days From Randomization
timeFrame: From randomization date to Day 100
measure: Time From Randomization to the First Onset of Proven or Probable IFI
timeFrame: From randomization date to Day 100
measure: Time From Randomization to Administration of First Systemic Antifungal Intravenous (IV) Therapy
timeFrame: Up to 12 weeks (84 days)
measure: Number of Participants With Clinical Failure During Treatment
timeFrame: Up to 12 weeks (84 days)
measure: Number of Participants in Whom All-cause Mortality Occurred Within 100 Days From Randomization
timeFrame: Randomization date to Day 100
measure: Number of Participants in Whom Mortality is Unlikely, Possibly, and Probably Related to Fungal Infection Occurred Within 100 Days From Randomization
timeFrame: From randomization date to Day 100
Other outcomes:
Locations:
Study officials:
References:
citation: Shen Y, Huang XJ, Wang JX, Jin J, Hu JD, Yu K, Wu DP, Wang SJ, Yu L, Chen XQ, Liu T, Liang YM, Chen FP, Li Y, Shen ZX. Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study. Int J Clin Pharmacol Ther. 2013 Sep;51(9):738-45. doi: 10.5414/CP201880.