Prophylaxis Of Invasive Fungal Infections
Conditions
Keywords
Invasive Fungal Infection, Allogenic Stem Cell Transplant, prophylaxis, leukemia, voriconazole
Brief summary
To prevent recurrence of invasive fungal infection in patients with allogeneic stem cell transplants
Interventions
DRUGvoriconazole
Voriconazole is given to patients at least 48 hours after chemotherapy
Sponsors
European Society for Blood and Marrow Transplantation
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with proven or probable IFI in previous 12 months receiving an allogenic stem cell transplant for any haematological disease
Exclusion criteria
* Pregnant or lactating women * Severe disease other tham the underlying condition * Active, symptomatic uncontrolled Invasive Fungal Infection * Any evidence of active fungal disease as defined by MSG-EORTC criteria * Concomitant use of Voriconazole 36 hours before chemotherapy until 48 hours after chemotherapy * Other medical conditions, including HIV positive serology that would interfere with the evaluation of therapeutic response or safety of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 12-month Follow-up Visit | 12 months | Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 12-month follow up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Voriconazole Prophylaxis Until End of Prophylaxis Visit | 150 days | Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until the End of Prophylaxis visit |
| Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI) | 12 months | Time to occurrence of proven or probable IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI since the exact day on which the IFI began will not be known. |
| Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 6-month Follow-up Visit | 6 months | Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 6-month follow up |
| Time to Occurrence of Proven or Probable Recurrent Invasive Fungal Infection (IFI) (Same Pathogen as Previous Baseline IFI) | 12 months | Time to occurrence of proven or probable recurrent (same pathogen as baseline) IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI. The pathogen identified as the positive culture recorded nearest to, but not after, the proven or probable IFI, was assumed to be responsible for the IFI. |
| Survival Without Proven or Probable Invasive Fungal Infection (IFI) | 6 months, 12 months | Number of participants who survive (ie., are alive) without proven or probable IFI at each of the 6 and 12 month follow-up visits |
| Time to Occurrence of Proven or Probable New (New Pathogen) Invasive Fungal Infection (IFI) | 12 months | Time to occurrence of proven or probable new (new pathogen) IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI. |
Countries
Belgium, France, Germany, Portugal, Spain, Sweden, Switzerland, United Kingdom
Participant flow
Pre-assignment details
Subjects with proven or probable Invasive Fungal Infection (IFI) in the previous 12 months, who were receiving an allogeneic Stem Cell Transplant (SCT) for any hematologic disease, were enrolled into the study if all other inclusion/exclusion criteria were met.
Participants by arm
| Arm | Count |
|---|---|
| Voriconazole All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed \<40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 11 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Voriconazole |
|---|---|
| Age Continuous | 48.4 years STANDARD_DEVIATION 14.1 |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 45 |
| serious Total, serious adverse events | 23 / 45 |
Outcome results
Primary
Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 12-month Follow-up Visit
Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 12-month follow up
Time frame: 12 months
Population: Complete case analysis (ie, outcome must be observed and/or subject must be evaluable for entire period of interest) using modified intent-to-treat (MITT) population (ie, subjects had at least 1 dose of voriconazole \& at least 1 post-enrollment efficacy assessment \& previous diagnosis of proven or probable IFI, confirmed by Data Review Committee).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Voriconazole | Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 12-month Follow-up Visit | 3 participants |
95% CI: [2, 19]
95% CI: [2, 27]
Secondary
Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 6-month Follow-up Visit
Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 6-month follow up
Time frame: 6 months
Population: Complete case analysis (ie, outcome must be observed and/or subject must be evaluable for entire period of interest) using modified intent-to-treat (MITT) population (ie, subjects had at least 1 dose of voriconazole \& at least 1 post-enrollment efficacy assessment \& previous diagnosis of proven or probable IFI, confirmed by Data Review Committee).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Voriconazole | Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 6-month Follow-up Visit | 3 participants |
95% CI: [2, 24]
Secondary
Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Voriconazole Prophylaxis Until End of Prophylaxis Visit
Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until the End of Prophylaxis visit
Time frame: 150 days
Population: Complete case analysis (ie, outcome must be observed and/or subject must be evaluable for entire period of interest) using modified intent-to-treat (MITT) population (ie, subjects had at least 1 dose of voriconazole \& at least 1 post-enrollment efficacy assessment \& previous diagnosis of proven or probable IFI, confirmed by Data Review Committee).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Voriconazole | Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Voriconazole Prophylaxis Until End of Prophylaxis Visit | 3 participants |
95% CI: [2, 24]
Secondary
Survival Without Proven or Probable Invasive Fungal Infection (IFI)
Number of participants who survive (ie., are alive) without proven or probable IFI at each of the 6 and 12 month follow-up visits
Time frame: 6 months, 12 months
Population: Complete case analysis using MITT population (ie, all subjects who had at least 1 dose of study medication \& at least 1 post-enrollment efficacy assessment \& a previous diagnosis of proven or probable IFI, confirmed by Data Review Committee) \& either provided an IFI assessment at follow-up visit, died or experienced an IFI before that visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Voriconazole | Survival Without Proven or Probable Invasive Fungal Infection (IFI) | survived free of IFI until 6 months | 31 participants |
| Voriconazole | Survival Without Proven or Probable Invasive Fungal Infection (IFI) | survived free of IFI until 12 months | 27 participants |
95% CI: [64, 91]
95% CI: [52, 83]
Secondary
Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI)
Time to occurrence of proven or probable IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI since the exact day on which the IFI began will not be known.
Time frame: 12 months
Population: Modified intent-to-treat (MITT) population (considered evaluable for efficacy) consisted of all subjects who had at least 1 dose of voriconazole \& at least 1 post-enrollment efficacy assessment \& had a previous diagnosis of proven or probable IFI, confirmed by the Data Review Committee. Three subjects in the MITT population experienced an IFI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Voriconazole | Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI) | time to recurrent IFI (third subject) | 81 days |
| Voriconazole | Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI) | time to recurrent IFI (first subject) | 6 days |
| Voriconazole | Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI) | time to recurrent IFI (second subject) | 22 days |
Secondary
Time to Occurrence of Proven or Probable New (New Pathogen) Invasive Fungal Infection (IFI)
Time to occurrence of proven or probable new (new pathogen) IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI.
Time frame: 12 months
Population: Modified intent-to-treat (MITT) population (considered evaluable for efficacy) consisted of all subjects who had at least 1 dose of voriconazole \& at least 1 post-enrollment efficacy assessment \& had a previous diagnosis of proven or probable IFI, confirmed by the Data Review Committee. One subject in the MITT population experienced a new IFI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Voriconazole | Time to Occurrence of Proven or Probable New (New Pathogen) Invasive Fungal Infection (IFI) | 81 days |
Secondary
Time to Occurrence of Proven or Probable Recurrent Invasive Fungal Infection (IFI) (Same Pathogen as Previous Baseline IFI)
Time to occurrence of proven or probable recurrent (same pathogen as baseline) IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI. The pathogen identified as the positive culture recorded nearest to, but not after, the proven or probable IFI, was assumed to be responsible for the IFI.
Time frame: 12 months
Population: Modified intent-to-treat (MITT) population (considered evaluable for efficacy) consisted of all subjects who had at least 1 dose of voriconazole \& at least 1 post-enrollment efficacy assessment \& had a previous diagnosis of proven or probable IFI, confirmed by the Data Review Committee. Two subjects experienced a recurrent proven or probable IFI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Voriconazole | Time to Occurrence of Proven or Probable Recurrent Invasive Fungal Infection (IFI) (Same Pathogen as Previous Baseline IFI) | time to IFI (first subject) | 6 days |
| Voriconazole | Time to Occurrence of Proven or Probable Recurrent Invasive Fungal Infection (IFI) (Same Pathogen as Previous Baseline IFI) | time to IFI (second subject) | 22 days |