Amphotericin-B and Voriconazole for Pulmonary Blastomycosis (BLASTO)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02283905|
Recruitment Status : Terminated (Poor enrollment numbers of patients)
First Posted : November 5, 2014
Last Update Posted : September 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|Blastomycosis||Drug: amphotericin-B Drug: voriconazole||Phase 4|
To evaluate six intensively studied patients admitted to medical intensive care with pulmonary blastomycosis requiring mechanical ventilation. Interventionally, all patients will receive continuously infused amphotericin-B (1 mg/kg/d); and then stepped down to oral or i.v. voriconazole once clinically responding. Blood will be sampled for amphotericin-B concentrations for the 3 first days (i.e. one blood sample per day); and when eventually changed over to voriconazole (i.e. generally after a total dose of 1 g has been reached of Amphotericin-B; as per usual practice). Once switched to oral or intravenous voriconazole, at the treating physicians discretion, then blood would once again be sampled for the next 3 days for voriconazole concentrations. MIC's of the infecting blastomyces would also be analyzed. The fungal isolate would be sent off to the Fungus Testing Laboratory at the University of Texas in San Antonio for susceptibility testing.
Clinical response to therapy relative to their initial pharmacokinetic and pharmacodynamic indices for amphotericin-B (i.e. daily free maximal concentration divided by the MIC) would be assessed in these 6 intensively studied patients. Clinical parameters assessed would be 1). time to fever defervescence; 2). time to white cell count resolution, and 3). improvements in respiratory gas exchange (i.e. specifically the rate of rise of the pressure of arterial oxygen (Pa02) divided by the fraction of inspired oxygen (Fi02) delivered through the ventilator (or PF ratio).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Case Series of Continuously-infused Amphotericin-B and Follow-up Voriconazole Therapy for Severe Blastomycosis Pulmonary Infections|
|Actual Study Start Date :||June 2015|
|Actual Primary Completion Date :||September 25, 2020|
|Actual Study Completion Date :||September 25, 2020|
Amphotericin-B and Voriconazole
Treatment with a 24 hour continuous infusion of amphotericin B deoxycholate at 1.0 mg/kg/day for a total dose of at least 1 g (i.e. ~ 14 days); and then the patient is stepped down to voriconazole 6 mg/kg i.v. q12h for 2 doses, then 4 mg/kg q12h either i.v. or orally as appropriate. The oral dose will be rounded for convenience to either the 200 mg or 400 mg tablet twice daily.
Other Name: Fungizone
intravenously or orally administered
Other Name: Vfend
- The concentration-time profile of antifungals during treatment relative to the level of susceptibility of the infecting organism [ Time Frame: within the first month of therapy ]
- Clinical recovery - as assessed by time to fever defervescence; and white blood cell (WBC) count resolution [ Time Frame: 2 to 3 days ]Temperature would be assessed at least 4 times daily; and once there was a sustained temp < 38 degrees Celsius the timing would stop. WBC would be assessed at least twice daily and once the count fell less than 12,000 the timing would stop.
- Clinical recovery - time to discontinuation of mechanical ventilation [ Time Frame: less than 7 days ]Defined as the interval between initiation of amphotericin-B infusion and when the patient was considered ready for extubation. A patient was considered ready for extubation if awake or arousable, neurologically intact, cooperative and comfortable, fraction of inspired oxygen (FiO2) < or = 0.4, positive end-expiratory pressure (PEEP) < or = 5 cm water (H2O); and at the attending physicians discretion. Patient status will be assessed for extubation at least once daily.
- Clinical recovery - time to respiratory dysfunction resolution [ Time Frame: less than 4 days ]The daily assessment of the lowest pressure of arterial oxygen divided by the fraction of inspired oxygen (PF ratio = Pa02/Fi02) to detect the time until the PF ratio exceeds 200
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02283905
|St. Boniface General Hospital|
|Winnipeg, Manitoba, Canada, R2H 2A6|
|Principal Investigator:||Robert E. Ariano, Pharm.D.||St. Boniface Hospital|