BlastomycosisPhase 4BLASTONCT02283905
Amphotericin-B and Voriconazole for Pulmonary Blastomycosis
A Phase 4 study testing amphotericin-B and voriconazole in people with Blastomycosis, run by University of Manitoba at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Blastomycosis
- What is being tested?
- amphotericin-B and voriconazole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2015to 25 Sep 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- The patient's data will be excluded if they die within 3 days of hospital admission.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Case Series of Continuously-infused Amphotericin-B and Follow-up Voriconazole Therapy for Severe Blastomycosis Pulmonary Infections
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.
Read the 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).
- Conditions
- Blastomycosis
- Being tested
- amphotericin-B, voriconazole
- Keywords
- amphotericin-B, continuously infused, voriconazole
- Medical subject headings
- Blastomycosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
amphotericin-BDrug
Also called Fungizone
continuously infused
voriconazoleDrug
Also called Vfend
intravenously or orally administered
| Study group | Role | What they receive |
|---|---|---|
| Amphotericin-B and Voriconazole | Other | 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. Receives: Drug: amphotericin-B; Drug: voriconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
The concentration-time profile of antifungals during treatment relative to the level of susceptibility of the infecting organism
Measured: within the first month of therapy
Secondary outcomes (3)
Clinical recovery - as assessed by time to fever defervescence; and white blood cell (WBC) count resolution
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.
Measured: 2 to 3 days
Clinical recovery - time to discontinuation of mechanical ventilation
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.
Measured: less than 7 days
Clinical recovery - time to respiratory dysfunction resolution
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
Measured: less than 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2014 (estimated)
- Study startJun 2015
- Primary completion25 Sep 2020
- Study completion25 Sep 2020
Why it stopped: Poor enrollment numbers of patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for BlastomycosisStudies of the same condition, open and under way.
- More trials run by University of ManitobaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Robert Ariano, University of Manitoba
- Investigators
- Robert E. Ariano, Pharm.D., Principal investigator, St. Boniface Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02283905
- Sponsor's protocol ID
- B2014:032
- Acronym
- BLASTO
- Status last verified
- Sep 2020
- First submitted
- 31 Oct 2014
- Last updated
- 29 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, Threlkeld MG, Kauffman CA; Infectious Diseases Society of America. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Jun 15;46(12):1801-12. doi: 10.1086/588300.
PubMed 18462107Chowfin A, Tight R, Mitchell S. Recurrent blastomycosis of the central nervous system: case report and review. Clin Infect Dis. 2000 Jun;30(6):969-71. doi: 10.1086/313828.
PubMed 10880319Ariano RE, Mitchelmore BR, Lagace-Wiens PR, Zelenitsky SA. Successful treatment of pulmonary blastomycosis with continuously infused amphotericin B deoxycholate after failure with liposomal amphotericin B. Ann Pharmacother. 2013 Jun;47(6):e26. doi: 10.1345/aph.1R703. Epub 2013 May 14.
PubMed 23673538Eriksson U, Seifert B, Schaffner A. Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial. BMJ. 2001 Mar 10;322(7286):579-82. doi: 10.1136/bmj.322.7286.579.
PubMed 11238151
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Case Series of Continuously-infused Amphotericin-B and Follow-up Voriconazole Therapy for Severe Blastomycosis Pulmonary Infections
- ClinicalTrials.gov ID
- NCT02283905
- Acronym / sponsor ID
- BLASTO / B2014:032
- Conditions
- Blastomycosis
- Keywords
- amphotericin-B, continuously infused, voriconazole
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor enrollment numbers of patients
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Jun 2015 (actual)
- Primary completion
- 25 Sep 2020 (actual)
- Study completion
- 25 Sep 2020 (actual)
- First posted
- 5 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Amphotericin-B and Voriconazole | Other | Drug: amphotericin-B, Drug: voriconazoleTreatment 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- The patient's data will be excluded if they die within 3 days of hospital admission.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| amphotericin-BAlso: Fungizonecontinuously infused | Drug | Amphotericin-B and Voriconazole |
| voriconazoleAlso: Vfendintravenously or orally administered | Drug | Amphotericin-B and Voriconazole |
Primary outcome
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
3 secondary outcomes
Clinical recovery - as assessed by time to fever defervescence; and white blood cell (WBC) count resolution
Time frame: 2 to 3 days
Clinical recovery - time to discontinuation of mechanical ventilation
Time frame: less than 7 days
Clinical recovery - time to respiratory dysfunction resolution
Time frame: less than 4 days
Results and safety
The study was stopped early (reason given: Poor enrollment numbers of patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2020.
- Background: PubMed 18462107Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, Threlkeld MG, Kauffman CA; Infectious Diseases Society of America. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Jun 15;46(12):1801-12. doi: 10.1086/588300.
- Background: PubMed 10880319Chowfin A, Tight R, Mitchell S. Recurrent blastomycosis of the central nervous system: case report and review. Clin Infect Dis. 2000 Jun;30(6):969-71. doi: 10.1086/313828.
- Background: PubMed 23673538Ariano RE, Mitchelmore BR, Lagace-Wiens PR, Zelenitsky SA. Successful treatment of pulmonary blastomycosis with continuously infused amphotericin B deoxycholate after failure with liposomal amphotericin B. Ann Pharmacother. 2013 Jun;47(6):e26. doi: 10.1345/aph.1R703. Epub 2013 May 14.
- Background: PubMed 11238151Eriksson U, Seifert B, Schaffner A. Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial. BMJ. 2001 Mar 10;322(7286):579-82. doi: 10.1136/bmj.322.7286.579.
- Individual participant dataSharing planned: No
Related trials for Blastomycosis
Not yet recruitingPhase 2
Platform Trial for Salvage Consolidation Therapy in Dimorphic Fungi
Coccidioidomycosis, Blastomycosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert E. Ariano, Pharm.D. principal investigator
St. Boniface Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing amphotericin-B and voriconazole in people with Blastomycosis, run by University of Manitoba at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor enrollment numbers of patients). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02283905, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2020.