Amphotericin-B and Voriconazole for Pulmonary Blastomycosis (BLASTO)

University of Manitoba

Status and phase: Terminated; Phase 4

Conditions: Blastomycosis

Treatments: Drug: voriconazole; Drug: amphotericin-B

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02283905

B2014:032

Details and patient eligibility

About

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.

Full 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).

Enrollment: 2 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

Amphotericin-B and Voriconazole

Other group

Description:

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.

Treatment:

Drug: amphotericin-B

Drug: voriconazole