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Trial record 1 of 1 for:    NCT02283905
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Amphotericin-B and Voriconazole for Pulmonary Blastomycosis (BLASTO)

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ClinicalTrials.gov Identifier: NCT02283905
Recruitment Status : Terminated (Poor enrollment numbers of patients)
First Posted : November 5, 2014
Last Update Posted : September 29, 2020
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Robert Ariano, University of Manitoba

Tracking Information
First Submitted Date  ICMJE October 31, 2014
First Posted Date  ICMJE November 5, 2014
Last Update Posted Date September 29, 2020
Actual Study Start Date  ICMJE June 2015
Actual Primary Completion Date September 25, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2014)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2014)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Amphotericin-B and Voriconazole for Pulmonary Blastomycosis
Official Title  ICMJE Case Series of Continuously-infused Amphotericin-B and Follow-up Voriconazole Therapy for Severe Blastomycosis Pulmonary Infections
Brief Summary All patients with pulmonary blastomycosis requiring mechanical ventilation will have their blood concentrations measured for the antifungal drugs, amphotericin-B and voriconazole; as well as an analysis of the susceptibility of their infecting species of blastomyces. This information will then be analyzed relative to their rate of clinical recovery from this serious fungal infection.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Blastomycosis
Intervention  ICMJE
  • Drug: amphotericin-B
    continuously infused
    Other Name: Fungizone
  • Drug: voriconazole
    intravenously or orally administered
    Other Name: Vfend
Study Arms  ICMJE 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.
Interventions:
  • Drug: amphotericin-B
  • Drug: voriconazole
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 25, 2020)
2
Original Estimated Enrollment  ICMJE
 (submitted: November 4, 2014)
6
Actual Study Completion Date  ICMJE September 25, 2020
Actual Primary Completion Date September 25, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All adult patients 18 years of age or older admitted to the intensive care units of St. Boniface General Hospital with a diagnosis of acute pulmonary blastomycosis requiring mechanical ventilation.

Exclusion Criteria:

  • The patient's data will be excluded if they die within 3 days of hospital admission.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02283905
Other Study ID Numbers  ICMJE B2014:032
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Robert Ariano, University of Manitoba
Study Sponsor  ICMJE University of Manitoba
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Robert E. Ariano, Pharm.D. St. Boniface Hospital
PRS Account University of Manitoba
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP