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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

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.

Condition or disease Intervention/treatment Phase
Blastomycosis Drug: amphotericin-B Drug: voriconazole Phase 4

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.
Drug: amphotericin-B
continuously infused
Other Name: Fungizone

Drug: voriconazole
intravenously or orally administered
Other Name: Vfend




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

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


Locations
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Canada, Manitoba
St. Boniface General Hospital
Winnipeg, Manitoba, Canada, R2H 2A6
Sponsors and Collaborators
University of Manitoba
Pfizer
Investigators
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Principal Investigator: Robert E. Ariano, Pharm.D. St. Boniface Hospital
Publications:
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Responsible Party: Robert Ariano, Professor of Pharmacy and Medicine, Critical Care Pharmacist, University of Manitoba
ClinicalTrials.gov Identifier: NCT02283905    
Other Study ID Numbers: B2014:032
First Posted: November 5, 2014    Key Record Dates
Last Update Posted: September 29, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Robert Ariano, University of Manitoba:
amphotericin-B
continuously infused
voriconazole
Additional relevant MeSH terms:
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Blastomycosis
Dermatomycoses
Skin Diseases, Infectious
Infection
Mycoses
Lung Diseases, Fungal
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Skin Diseases
Voriconazole
Amphotericin B
Liposomal amphotericin B
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Bacterial Agents