Possible Fungal Infection
Conditions
Keywords
Neutropenia, Fever of unknown origin, Empirical treatment, Voriconazole
Brief summary
A well-known side-effect of cytostatics (drugs against malignancies) is a decrease in the number of white blood cells, especially of the so-called neutrophil granulocytes, which are very important for the defense against infections. Hence their decrease (called neutropenia) leads to a predisposition to infections. Since infections during neutropenia can be very dangerous, the patients are treated with antibiotics from the very first signs of such an infection (usually fever). If the antibiotics (drugs against bacteria) do not lead to a normalization of the body temperature within four days, a drug against fungi is added. In the IDEA study, one half of the patients receive the antifungal drug voriconazole (as usual) only in case the antibiotics alone do not lead to a normalization of the body temperature (current standard of care). The other half of the patients receive voriconazole immediately after onset of fever (concomitantly with the antibiotics). The research question is, whether in the early-treatment group fewer manifest fungal infections will be observed than in the late-treatment group.
Interventions
voriconazole, early treatment
Sponsors
Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Acute leukemia, aggressive lymphoma, bone marrow or stem cell transplantation; * Neutropenia (\<500 neutrophils/µL) of at least 10 days; * Newly diagnosed fever; * Positive panfungal polymerase chain reaction assay
Exclusion criteria
* Documented bacterial infection during screening or at randomization * Fungemia or other documented invasive fungal infection during screening or at randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis | Day 2 through Day 28 | Number of participants with proven (deep tissue infection, fungemia, or endemic fungal infections) or probable IFI (at least 1 host criterion \[fever, body temperature \<36 or \>38 degrees Celsius, graft-versus-host disease, use of corticosteroids\]; and 1 microbiological criterion \[fungal or yeasts\]; or clinical criteria \[abnormal site consistent with infection\]) as defined by European Organization for Research and Treatment of Cancer Mycosis Study Group (EORTC/MSG) criteria. Complete case analysis: must be evaluable until Day 28 or had developed a proven or probable IFI by the final visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Defervescence Day 9 (8 Days After Initiation of Study Treatment) | Day 9 (192 hours through 216 hours after start of study treatment) | Number of participants who achieved defervescence (were afebrile). Defervescence stated if all of a participant's body temperatures within 24 hours of evaluation time were \<38.0 degrees C. Defervescence was not stated and participant was discontinued from the study if participant received antipyretics (non-steroidal anti-inflammatory drugs or paracetamol). |
| Time to Continuous Defervescence | Day 2 through Day 28 | Time (in days) from start of study medication to continuous defervescence. Continuous defervescence stated if participant maintains a body temperature of \<38.0 degrees C for at least 96 hours. |
| Number of Participants Per Reason for Lack of Defervescence | Day 2 through Day 28 | — |
| Number of Participants That Died on or Before Day 28 (Mortality) | Day 2 through Day 28 | Number of participants that died on or before Day 28 after start of study treatment. A participant must be evaluable until Day 28 (final visit) or have died before the final visit. |
| Time to Negative Panfungal Polymerase Chain Reaction (PCR) | Day 2 through Day 28 | Time (in days) from start of study medication to negative panfungal PCR; assessed for participants whose most recent panfungal PCR result prior to start of study medication was positive. Defined as negative if at least 2 successive and all following panfungal PCR assessments from start of study medication until 24 hours after end of treatment are negative. Measured as first quartile of time (point in time measurement; no median or measure of dispersion calculated); median time was not estimable for deferred voriconazole treatment group. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (Yes) | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with achievement of continuous defervescence (response=Yes). Continuous defervescence stated if participant maintains a body temperature of \<38.0 degrees C for at least 96 hours. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (No) | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with achievement of continuous defervescence (response=No). Continuous defervescence stated if participant maintains a body temperature of \<38.0 degrees C for at least 96 hours. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Age | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with age for participants who completed the study and have a non-missing value for percent of positive panfungal PCR. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with gender (Female or Male). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with primary underlying neoplastic disease. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with allogeneic bone marrow transplant or allogeneic peripheral stem cell transplant (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole | Day 2 through Day 28 | Percent positive panfungal PCR assessments during treatment phase of study in association with use of concomitant (prophylaxis) fluconazole (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with neutrophil count \>500 uL (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Number of Participants With Defervescence Day 5 (4 Days After Initiation of Study Treatment) | Day 5 (96 hours through 120 hours after start of study treatment) | Number of participants who achieved defervescence (were afebrile). Defervescence stated if all of a participants's body temperatures within 24 hours of evaluation time were \<38.0 degrees C. Defervescence was not stated and participant was discontinued from the study if participant received antipyretics (non-steroidal anti-inflammatory drugs or paracetamol). |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with fungal species (singular \[one species\]=sp; plural \[many species\]=spp) identified (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified (Aspergillus Spp=Yes) | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with fungal species (singular \[one species\]=sp; plural \[many species\]=spp) identified (Yes). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Proven or Probable IFI (Complete Cases) Between Day 2 and Day 28 | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with proven or probable IFI (complete cases) between Day 2 and Day 28 (Yes or No). Complete case analysis: participant must be evaluable until Day 28 (final visit) or have developed a proven or probable IFI by the final visit. Participant considered evaluable until Day 28 if participant completed the study and completed an assessment of IFI at Day 28 or final visit. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence Day 5 (4 Days After Initiation of Study Treatment) | Day 5 (96 hours through 120 hours after start of study treatment) | Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 5 (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (Yes) by Day 9 (8 Days After Initiation of Study Treatment) | Day 2 through Day 9 (192 hours through 216 hours after start of study treatment) | Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 9 (Yes). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (No) by Day 9 (8 Days After Initiation of Study Treatment) | Day 2 through Day 9 (192 hours through 216 hours after start of study treatment) | Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 9 (No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Time to Defervescence | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with time to defervescence. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with lack of continuous defervescence (No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence: Unknown Infection (Yes) | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with lack of continuous defervescence (Yes). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Alive) | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with mortality on or before Day 28 after start of study treatment (Alive). A participant must be evaluable until Day 28 (final visit). |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Died) | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with mortality on or before Day 28 after start of study treatment (Died). A participant must have died before Day 28 (final visit). |
| Number of Participants Assessed as Needing Further Antineoplastic Therapy as Planned | Day 28 | — |
| Number of Participants With Reasons Why Antineoplastic Therapy Not Continued as Planned | Day 28 | — |
| Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With C-reactive Protein Level >1.25 Times the Upper Limit of Normal (x ULN) | Day 2 through Day 28 | Percent of positive panfungal PCR assessments during treatment phase of study in association with c-reactive protein level (measured in milligrams per liter \[mg/L\]) \>1.25 x ULN (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100. |
Countries
Germany
Participant flow
Recruitment details
810 participants screened; 81 assigned to immediate voriconazole treatment and 66 to deferred voriconazole treatment. Study should be considered a pilot study; planned sample size (n=200) was not based on statistical power considerations.
Pre-assignment details
Screening phase started with cytoreductive treatment; screening phase ended at onset of fever or if reconstitution of leukocytes to \>1000 per microliter (1000/uL) or neutrophils to \>500/uL. Randomization occurred within 18 hours after onset of fever (if febrile or had positive polymerase chain reaction (PCR) assay prior to onset of fever).
Participants by arm
| Arm | Count |
|---|---|
| Immediate Voriconazole Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (\< 38.0 degrees Celsius \[C\]) for 7 days with neutrophil counts \< 500 per microliter (500/uL) or if participant was afebrile (\< 38.0 degrees C) for 2 days with neutrophil counts \> 500/uL. | 81 |
| Deferred Voriconazole Treatment Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (\< 38.0 degrees C) for 7 days with neutrophil counts \< 500/uL or if participant was afebrile (\< 38.0 degrees C) for 2 days with neutrophil counts \> 500/uL. | 66 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 6 |
| Overall Study | Death | 5 | 2 |
| Overall Study | Laboratory abnormality | 1 | 2 |
| Overall Study | Lack of Efficacy | 5 | 4 |
| Overall Study | Other | 12 | 14 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Total | Deferred Voriconazole Treatment | Immediate Voriconazole |
|---|---|---|---|
| Age, Customized >=65 years | 35 participants | 14 participants | 21 participants |
| Age, Customized Between 18 and 44 years | 46 participants | 17 participants | 29 participants |
| Age, Customized Between 45 and 64 years | 66 participants | 35 participants | 31 participants |
| Height | 172.0 centimeters (cm) | 171.9 centimeters (cm) | 172.1 centimeters (cm) |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 146 participants | 65 participants | 81 participants |
| Sex: Female, Male Female | 68 Participants | 29 Participants | 39 Participants |
| Sex: Female, Male Male | 79 Participants | 37 Participants | 42 Participants |
| Weight | 78.1 kilograms (kg) | 79.2 kilograms (kg) | 77.1 kilograms (kg) |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 81 | 38 / 66 |
| serious Total, serious adverse events | 8 / 81 | 8 / 66 |
Outcome results
Primary
Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis
Number of participants with proven (deep tissue infection, fungemia, or endemic fungal infections) or probable IFI (at least 1 host criterion \[fever, body temperature \<36 or \>38 degrees Celsius, graft-versus-host disease, use of corticosteroids\]; and 1 microbiological criterion \[fungal or yeasts\]; or clinical criteria \[abnormal site consistent with infection\]) as defined by European Organization for Research and Treatment of Cancer Mycosis Study Group (EORTC/MSG) criteria. Complete case analysis: must be evaluable until Day 28 or had developed a proven or probable IFI by the final visit.
Time frame: Day 2 through Day 28
Population: Modified Intent-to-Treat population (MITT): participants in ITT population (at least 1 dose of study treatment) with valid post-baseline proven or probable IFI, did not have fungemia or other IFI at screening or randomization, no antipyretic analgesics on Day 5 (or Day 9 of open-label voriconazole). N=number of complete case evaluable participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Voriconazole | Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis | 6 participants |
| Deferred Voriconazole Treatment | Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis | 9 participants |
Comparison: Hypothesis: H0: rv - rp = 0 vs H1: rv - rp does not equal 0, where ri is rate of IFI (i=v for voriconazole group, i=p for deferred voriconazole group). Logit model (including important covariates) used. The adjusted odds ratio and 95 percent (%) confidence interval (CI) for adjusted odds ratio calculated. If 95% CI around odds ratio does not contain a value of 1, then the null hypothesis of equal rates of IFI between immediate voriconazole and deferred voriconazole to be rejected.p-value: 0.25895% CI: [0.129, 1.755]Regression, Logistic
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (No)
Percent of positive panfungal PCR assessments during treatment phase of study in association with achievement of continuous defervescence (response=No). Continuous defervescence stated if participant maintains a body temperature of \<38.0 degrees C for at least 96 hours. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (No) | 21.7 percent of positive PCR assessments | Standard Deviation 20.21 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (Yes)
Percent of positive panfungal PCR assessments during treatment phase of study in association with achievement of continuous defervescence (response=Yes). Continuous defervescence stated if participant maintains a body temperature of \<38.0 degrees C for at least 96 hours. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (Yes) | 10.6 percent of positive PCR assessments | Standard Deviation 14.11 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (Yes) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
Comparison: Continuous defervescence achieved=Yesp-value: 0.04995% CI: [-44.004, -0.059]Regression, Linear
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Age
Percent of positive panfungal PCR assessments during treatment phase of study in association with age for participants who completed the study and have a non-missing value for percent of positive panfungal PCR.
Time frame: Day 2 through Day 28
Population: MITT. Correlation of positive panfungal PCR assessments with age was not summarized as planned.
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole
Percent positive panfungal PCR assessments during treatment phase of study in association with use of concomitant (prophylaxis) fluconazole (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole | Association Yes (n=8, 4) | 13.5 percent of positive PCR assessments | Standard Deviation 15.39 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole | Association No (n=31, 23) | 10.9 percent of positive PCR assessments | Standard Deviation 14.63 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole | Association Yes (n=8, 4) | 6.3 percent of positive PCR assessments | Standard Deviation 12.5 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole | Association No (n=31, 23) | 8.3 percent of positive PCR assessments | Standard Deviation 15.28 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With C-reactive Protein Level >1.25 Times the Upper Limit of Normal (x ULN)
Percent of positive panfungal PCR assessments during treatment phase of study in association with c-reactive protein level (measured in milligrams per liter \[mg/L\]) \>1.25 x ULN (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT. Correlation of positive panfungal PCR assessments with c-reactive protein level was not summarized as planned.
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence Day 5 (4 Days After Initiation of Study Treatment)
Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 5 (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 5 (96 hours through 120 hours after start of study treatment)
Population: MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence Day 5 (4 Days After Initiation of Study Treatment) | Association Yes (n=28, 21) | 14.5 percent of positive PCR assessments | Standard Deviation 14.58 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence Day 5 (4 Days After Initiation of Study Treatment) | Association No (n=11, 6) | 3.6 percent of positive PCR assessments | Standard Deviation 12.06 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence Day 5 (4 Days After Initiation of Study Treatment) | Association Yes (n=28, 21) | 8.3 percent of positive PCR assessments | Standard Deviation 15.81 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence Day 5 (4 Days After Initiation of Study Treatment) | Association No (n=11, 6) | 6.9 percent of positive PCR assessments | Standard Deviation 11.08 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (No) by Day 9 (8 Days After Initiation of Study Treatment)
Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 9 (No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 9 (192 hours through 216 hours after start of study treatment)
Population: MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (No) by Day 9 (8 Days After Initiation of Study Treatment) | 20.0 percent of positive PCR assessments | Standard Deviation 28.28 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (Yes) by Day 9 (8 Days After Initiation of Study Treatment)
Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 9 (Yes). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 9 (192 hours through 216 hours after start of study treatment)
Population: MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (Yes) by Day 9 (8 Days After Initiation of Study Treatment) | 11.0 percent of positive PCR assessments | Standard Deviation 14.11 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (Yes) by Day 9 (8 Days After Initiation of Study Treatment) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified
Percent of positive panfungal PCR assessments during treatment phase of study in association with fungal species (singular \[one species\]=sp; plural \[many species\]=spp) identified (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Aspergillus flavus: No (n=39, 27) | 11.4 percent of positive PCR assessments | Standard Deviation 14.62 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Aspergillus fumig: No (n=38, 27) | 11.7 percent of positive PCR assessments | Standard Deviation 14.7 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Aspergillus nidulans: No (n=39, 27) | 11.4 percent of positive PCR assessments | Standard Deviation 14.62 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Aspergillus sp: No (n=39, 27) | 11.4 percent of positive PCR assessments | Standard Deviation 14.62 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Aspergillus spp: No (n=37, 27) | 11.6 percent of positive PCR assessments | Standard Deviation 14.88 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida albicans: Yes (n=2, 4) | 16.7 percent of positive PCR assessments | Standard Deviation 23.57 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida albicans: No (n=37, 23) | 11.2 percent of positive PCR assessments | Standard Deviation 14.45 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida glabrata: Yes (n=2, 1) | 33.3 percent of positive PCR assessments | Standard Deviation 0 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida glabrata: No (n=37, 26) | 10.3 percent of positive PCR assessments | Standard Deviation 14.06 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida krusei: No (n=39, 26) | 11.4 percent of positive PCR assessments | Standard Deviation 14.62 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida spp: No (n=38, 27) | 11.7 percent of positive PCR assessments | Standard Deviation 14.7 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida tropicalis: No (n=39, 27) | 11.4 percent of positive PCR assessments | Standard Deviation 14.62 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida spp: No (n=38, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Aspergillus flavus: No (n=39, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida albicans: No (n=37, 23) | 9.4 percent of positive PCR assessments | Standard Deviation 15.55 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Aspergillus fumig: No (n=38, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida krusei: No (n=39, 26) | 8.3 percent of positive PCR assessments | Standard Deviation 14.91 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Aspergillus nidulans: No (n=39, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida glabrata: Yes (n=2, 1) | 0.0 percent of positive PCR assessments | Standard Deviation 0 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Aspergillus sp: No (n=39, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida tropicalis: No (n=39, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Aspergillus spp: No (n=37, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida glabrata: No (n=37, 26) | 8.3 percent of positive PCR assessments | Standard Deviation 14.91 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified | Candida albicans: Yes (n=2, 4) | 0.0 percent of positive PCR assessments | Standard Deviation 0 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified (Aspergillus Spp=Yes)
Percent of positive panfungal PCR assessments during treatment phase of study in association with fungal species (singular \[one species\]=sp; plural \[many species\]=spp) identified (Yes). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified (Aspergillus Spp=Yes) | 8.3 percent of positive PCR assessments | Standard Deviation 11.79 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender
Percent of positive panfungal PCR assessments during treatment phase of study in association with gender (Female or Male). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender | Female (n=21, 12) | 12.3 percent of positive PCR assessments | Standard Deviation 14.82 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender | Male (n=18, 15) | 10.4 percent of positive PCR assessments | Standard Deviation 14.75 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender | Female (n=21, 12) | 4.2 percent of positive PCR assessments | Standard Deviation 10.36 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender | Male (n=18, 15) | 11.1 percent of positive PCR assessments | Standard Deviation 17.16 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Alive)
Percent of positive panfungal PCR assessments during treatment phase of study in association with mortality on or before Day 28 after start of study treatment (Alive). A participant must be evaluable until Day 28 (final visit).
Time frame: Day 2 through Day 28
Population: MITT; participants who completed the study and had a non-missing value for percent of positive panfungal PCR. N=number of participants for category Alive.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Alive) | 11.4 percent of positive PCR assessments | Standard Deviation 14.62 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Alive) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Died)
Percent of positive panfungal PCR assessments during treatment phase of study in association with mortality on or before Day 28 after start of study treatment (Died). A participant must have died before Day 28 (final visit).
Time frame: Day 2 through Day 28
Population: MITT; participants who completed the study and had a non-missing value for percent of positive panfungal PCR: no participants met this criteria within the category Died.
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL
Percent of positive panfungal PCR assessments during treatment phase of study in association with neutrophil count \>500 uL (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL | Association Yes (n=24, 20) | 10.9 percent of positive PCR assessments | Standard Deviation 14.6 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL | Association No (n=15, 7) | 12.3 percent of positive PCR assessments | Standard Deviation 15.13 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL | Association Yes (n=24, 20) | 7.9 percent of positive PCR assessments | Standard Deviation 15.17 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL | Association No (n=15, 7) | 8.3 percent of positive PCR assessments | Standard Deviation 14.43 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants
Percent of positive panfungal PCR assessments during treatment phase of study in association with allogeneic bone marrow transplant or allogeneic peripheral stem cell transplant (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants | Association Yes (n=13, 9) | 10.5 percent of positive PCR assessments | Standard Deviation 14.88 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants | Association No (n=26, 18) | 11.9 percent of positive PCR assessments | Standard Deviation 14.77 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants | Association Yes (n=13, 9) | 6.5 percent of positive PCR assessments | Standard Deviation 13.03 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants | Association No (n=26, 18) | 8.8 percent of positive PCR assessments | Standard Deviation 15.78 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease
Percent of positive panfungal PCR assessments during treatment phase of study in association with primary underlying neoplastic disease. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease | Acute lymphatic leukemia (n=6, 6) | 13.9 percent of positive PCR assessments | Standard Deviation 16.39 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease | Acute myeloid leukemia (n=29, 18) | 10.5 percent of positive PCR assessments | Standard Deviation 14.39 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease | Acute lymphatic leukemia (n=6, 6) | 9.7 percent of positive PCR assessments | Standard Deviation 15.29 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease | Acute myeloid leukemia (n=29, 18) | 8.8 percent of positive PCR assessments | Standard Deviation 15.78 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Proven or Probable IFI (Complete Cases) Between Day 2 and Day 28
Percent of positive panfungal PCR assessments during treatment phase of study in association with proven or probable IFI (complete cases) between Day 2 and Day 28 (Yes or No). Complete case analysis: participant must be evaluable until Day 28 (final visit) or have developed a proven or probable IFI by the final visit. Participant considered evaluable until Day 28 if participant completed the study and completed an assessment of IFI at Day 28 or final visit. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Proven or Probable IFI (Complete Cases) Between Day 2 and Day 28 | Association Yes (n=2, 2) | 0.0 percent of positive PCR assessments | Standard Deviation 0 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Proven or Probable IFI (Complete Cases) Between Day 2 and Day 28 | Association No (n=37, 25) | 12.1 percent of positive PCR assessments | Standard Deviation 14.77 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Proven or Probable IFI (Complete Cases) Between Day 2 and Day 28 | Association Yes (n=2, 2) | 16.7 percent of positive PCR assessments | Standard Deviation 23.57 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Proven or Probable IFI (Complete Cases) Between Day 2 and Day 28 | Association No (n=37, 25) | 7.3 percent of positive PCR assessments | Standard Deviation 14.3 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No)
Percent of positive panfungal PCR assessments during treatment phase of study in association with lack of continuous defervescence (No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Bacterial infection: No (n=39, 27) | 11.4 percent of positive PCR assessments | Standard Deviation 14.62 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Unknown infection: No (n=36, 27) | 10.6 percent of positive PCR assessments | Standard Deviation 14.11 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Viral infection: No (n=39, 27) | 11.4 percent of positive PCR assessments | Standard Deviation 14.62 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Other infection: No (n=39, 27) | 11.4 percent of positive PCR assessments | Standard Deviation 14.62 |
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Fungal infection: No (n=39, 27) | 11.4 percent of positive PCR assessments | Standard Deviation 14.62 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Other infection: No (n=39, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Fungal infection: No (n=39, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Bacterial infection: No (n=39, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Viral infection: No (n=39, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
| Deferred Voriconazole Treatment | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No) | Unknown infection: No (n=36, 27) | 8.0 percent of positive PCR assessments | Standard Deviation 14.71 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence: Unknown Infection (Yes)
Percent of positive panfungal PCR assessments during treatment phase of study in association with lack of continuous defervescence (Yes). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immediate Voriconazole | Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence: Unknown Infection (Yes) | 21.7 percent of positive PCR assessments | Standard Deviation 20.21 |
Secondary
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Time to Defervescence
Percent of positive panfungal PCR assessments during treatment phase of study in association with time to defervescence. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time frame: Day 2 through Day 28
Population: MITT. Correlation of positive panfungal PCR assessments with time to defervescence was not summarized as planned.
Secondary
Number of Participants Assessed as Needing Further Antineoplastic Therapy as Planned
Time frame: Day 28
Population: MITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Voriconazole | Number of Participants Assessed as Needing Further Antineoplastic Therapy as Planned | 42 participants |
| Deferred Voriconazole Treatment | Number of Participants Assessed as Needing Further Antineoplastic Therapy as Planned | 32 participants |
Comparison: Difference in proportions expressed as a percent: immediate voriconazole vs deferred voriconazole treatment95% CI: [-14.96, 19.97]
Secondary
Number of Participants Per Reason for Lack of Defervescence
Time frame: Day 2 through Day 28
Population: MITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Immediate Voriconazole | Number of Participants Per Reason for Lack of Defervescence | Bacterial infection | 7 participants |
| Immediate Voriconazole | Number of Participants Per Reason for Lack of Defervescence | Fungal infection | 3 participants |
| Immediate Voriconazole | Number of Participants Per Reason for Lack of Defervescence | Viral infection | 1 participants |
| Immediate Voriconazole | Number of Participants Per Reason for Lack of Defervescence | Unknown | 4 participants |
| Immediate Voriconazole | Number of Participants Per Reason for Lack of Defervescence | Other | 3 participants |
| Immediate Voriconazole | Number of Participants Per Reason for Lack of Defervescence | Missing evaluation response | 0 participants |
| Deferred Voriconazole Treatment | Number of Participants Per Reason for Lack of Defervescence | Other | 3 participants |
| Deferred Voriconazole Treatment | Number of Participants Per Reason for Lack of Defervescence | Unknown | 4 participants |
| Deferred Voriconazole Treatment | Number of Participants Per Reason for Lack of Defervescence | Fungal infection | 3 participants |
| Deferred Voriconazole Treatment | Number of Participants Per Reason for Lack of Defervescence | Bacterial infection | 6 participants |
| Deferred Voriconazole Treatment | Number of Participants Per Reason for Lack of Defervescence | Missing evaluation response | 1 participants |
| Deferred Voriconazole Treatment | Number of Participants Per Reason for Lack of Defervescence | Viral infection | 0 participants |
Secondary
Number of Participants That Died on or Before Day 28 (Mortality)
Number of participants that died on or before Day 28 after start of study treatment. A participant must be evaluable until Day 28 (final visit) or have died before the final visit.
Time frame: Day 2 through Day 28
Population: MITT; N=number of participants evaluable until Day 28 (final visit) or died before the final visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Voriconazole | Number of Participants That Died on or Before Day 28 (Mortality) | 4 participants |
| Deferred Voriconazole Treatment | Number of Participants That Died on or Before Day 28 (Mortality) | 1 participants |
Comparison: Difference in proportions expressed as a percent: immediate voriconazole versus (vs) deferred voriconazole treatment95% CI: [-5.08, 16.78]
Secondary
Number of Participants With Defervescence Day 5 (4 Days After Initiation of Study Treatment)
Number of participants who achieved defervescence (were afebrile). Defervescence stated if all of a participants's body temperatures within 24 hours of evaluation time were \<38.0 degrees C. Defervescence was not stated and participant was discontinued from the study if participant received antipyretics (non-steroidal anti-inflammatory drugs or paracetamol).
Time frame: Day 5 (96 hours through 120 hours after start of study treatment)
Population: MITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Voriconazole | Number of Participants With Defervescence Day 5 (4 Days After Initiation of Study Treatment) | 32 participants |
| Deferred Voriconazole Treatment | Number of Participants With Defervescence Day 5 (4 Days After Initiation of Study Treatment) | 28 participants |
p-value: 0.59695% CI: [0.398, 1.696]Regression, Logistic
Secondary
Number of Participants With Defervescence Day 9 (8 Days After Initiation of Study Treatment)
Number of participants who achieved defervescence (were afebrile). Defervescence stated if all of a participant's body temperatures within 24 hours of evaluation time were \<38.0 degrees C. Defervescence was not stated and participant was discontinued from the study if participant received antipyretics (non-steroidal anti-inflammatory drugs or paracetamol).
Time frame: Day 9 (192 hours through 216 hours after start of study treatment)
Population: MITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Voriconazole | Number of Participants With Defervescence Day 9 (8 Days After Initiation of Study Treatment) | 42 particpants |
| Deferred Voriconazole Treatment | Number of Participants With Defervescence Day 9 (8 Days After Initiation of Study Treatment) | 34 particpants |
p-value: 0.86495% CI: [0.441, 1.988]Regression, Logistic
Secondary
Number of Participants With Reasons Why Antineoplastic Therapy Not Continued as Planned
Time frame: Day 28
Population: MITT; data not summarized as planned; data insufficient for analysis due to missing data.
Secondary
Time to Continuous Defervescence
Time (in days) from start of study medication to continuous defervescence. Continuous defervescence stated if participant maintains a body temperature of \<38.0 degrees C for at least 96 hours.
Time frame: Day 2 through Day 28
Population: MITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Immediate Voriconazole | Time to Continuous Defervescence | 6.0 days |
| Deferred Voriconazole Treatment | Time to Continuous Defervescence | 5.0 days |
p-value: 0.955Log Rank
Secondary
Time to Negative Panfungal Polymerase Chain Reaction (PCR)
Time (in days) from start of study medication to negative panfungal PCR; assessed for participants whose most recent panfungal PCR result prior to start of study medication was positive. Defined as negative if at least 2 successive and all following panfungal PCR assessments from start of study medication until 24 hours after end of treatment are negative. Measured as first quartile of time (point in time measurement; no median or measure of dispersion calculated); median time was not estimable for deferred voriconazole treatment group.
Time frame: Day 2 through Day 28
Population: MITT; N=number of participants whose most recent panfungal PCR result prior to start of study medication was positive.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Voriconazole | Time to Negative Panfungal Polymerase Chain Reaction (PCR) | 4.0 days |
| Deferred Voriconazole Treatment | Time to Negative Panfungal Polymerase Chain Reaction (PCR) | 5.5 days |
p-value: 0.19Log Rank