Aspergillosis
Conditions
Brief summary
The purpose of this study is to evaluate the relationship between fungal biomarker levels during anti-fungal therapy and the success of treatment for fungal infection. The primary hypothesis is that over the initial two weeks of anti-fungal therapy, fungal biomarkers from participants with invasive aspergillosis (IA) will be lower for those with a successful clinical outcome compared to those with a failed clinical outcome.
Interventions
OTHERNo Intervention
Blood samples will be collected for 12 weeks to evaluate levels of fungal biomarkers.
Sponsors
Merck Sharp & Dohme LLC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is 16 years of age or older * Female is either post-menopausal, surgically sterilized, willing to use 2 adequate methods of birth control, or agrees to abstain from heterosexual activity throughout the study * Female of child bearing potential must have a negative pregnancy test * Male is surgically sterilized, agrees to use an adequate method of contraception, or agrees to abstain from heterosexual activity for the duration of the study * Has possible, probable, or confirmed invasive aspergillosis (IA) * Has had a computed tomography (CT) or magnetic resonance imaging (MRI) scan 72 hours prior to initiation of anti-fungal therapy
Exclusion criteria
* Has had hemodialysis using cellulose membrane within 2 weeks of study start
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average of the Z-scores of the Time-Weighted Averages (TWA) of Fungal Biomarkers Galactomannan (GM) and (1,3)-β-D-glucan (βDG) Over the First Two Weeks of Treatment for Responders (R) and Non-Responders (NonR) to Anti-fungal Treatment at Week 6. | Weeks 1 and 2 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for biomarker analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA divided by the overall standard deviation (SD). The average of the Z-scores of the TWA for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average of the Z-scores of the TWA of the Changes From Baseline (CFB) of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | Weeks 1 and 2 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA CFB divided by the overall SD. The average of the Z-scores of the TWA CFB for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the Percent Changes From Baseline (%CFB) of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | Weeks 1 and 2 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for biomarker analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual %CFB divided by the overall SD. The average of the Z-scores of the %CFB for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | Weeks 1 and 2 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for biomarker analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the TWA of the CFB of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | Weeks 1 and 2 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA CFB divided by the overall SD. The average of the Z-scores of the TWA CFB for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | Week 1 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA divided by the overall SD. The average of the Z-scores of the TWA for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of %CFB of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | Weeks 1 and 2 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for biomarker analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual %CFB divided by the overall SD. The average of the Z-scores of the %CFB for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the Slopes of Least-Squares Straight Lines (SLSSL) Fitted to the Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | Weeks 1 and 2 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of biomarkers GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | Week 1 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA divided by the overall SD. The average of the Z-scores of the TWA for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | Week 1 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of biomarkers GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | Weeks 1 through 6 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA divided by the overall SD. The average of the Z-scores of the TWA for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | Weeks 1 through 6 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA divided by the overall SD. The average of the Z-scores of the TWA for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | Weeks 1 through 6 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of biomarkers GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | Weeks 1 through 6 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of biomarkers GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
| Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | Week 1 | After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of biomarkers GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Invasive Aspergillosis Participants who enrolled with a presumptive diagnosis of possible, probable or proven IA infection, were started on standard of care antifungal therapy. Within 14 days of the start of therapy participants were re-evaluated, and those diagnosed with possible IA were discontinued from the study, while those with probable and proven IA were defined as the baseline population | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 2 Weeks After Start Anti-fungal Therapy | Diagnosed with Possible IA | 65 |
Baseline characteristics
| Characteristic | Invasive Aspergillosis |
|---|---|
| Age, Continuous | 56.9 years STANDARD_DEVIATION 13.3 |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 116 |
| serious Total, serious adverse events | 0 / 116 |
Outcome results
Primary
Average of the Z-scores of the Time-Weighted Averages (TWA) of Fungal Biomarkers Galactomannan (GM) and (1,3)-β-D-glucan (βDG) Over the First Two Weeks of Treatment for Responders (R) and Non-Responders (NonR) to Anti-fungal Treatment at Week 6.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for biomarker analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA divided by the overall standard deviation (SD). The average of the Z-scores of the TWA for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 and 2
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and whose clinical outcome was determined at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the Time-Weighted Averages (TWA) of Fungal Biomarkers Galactomannan (GM) and (1,3)-β-D-glucan (βDG) Over the First Two Weeks of Treatment for Responders (R) and Non-Responders (NonR) to Anti-fungal Treatment at Week 6. | 0.20 Average Z-Score | Standard Deviation 1.32 |
| Responders | Average of the Z-scores of the Time-Weighted Averages (TWA) of Fungal Biomarkers Galactomannan (GM) and (1,3)-β-D-glucan (βDG) Over the First Two Weeks of Treatment for Responders (R) and Non-Responders (NonR) to Anti-fungal Treatment at Week 6. | -0.09 Average Z-Score | Standard Deviation 0.61 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.16690% CI: [-0.2, 0.77]t-test, 1 sided
Secondary
Average of the Z-scores of %CFB of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for biomarker analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual %CFB divided by the overall SD. The average of the Z-scores of the %CFB for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 and 2
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of %CFB of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | 0.31 Average Z-Score | Standard Deviation 1.4 |
| Responders | Average of the Z-scores of %CFB of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | -0.16 Average Z-Score | Standard Deviation 0.46 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.05490% CI: [-0.01, 0.96]t-test, 1 sided
Secondary
Average of the Z-scores of the Percent Changes From Baseline (%CFB) of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for biomarker analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual %CFB divided by the overall SD. The average of the Z-scores of the %CFB for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 and 2
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the Percent Changes From Baseline (%CFB) of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | 0.02 Average Z-Score | Standard Deviation 1.06 |
| Responders | Average of the Z-scores of the Percent Changes From Baseline (%CFB) of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | -0.00 Average Z-Score | Standard Deviation 0.79 |
Comparison: Mean Difference Between Non-Responders and Respondersp-value: 0.45790% CI: [-0.42, 0.47]t-test, 1 sided
Secondary
Average of the Z-scores of the Slopes of Least-Squares Straight Lines (SLSSL) Fitted to the Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of biomarkers GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 and 2
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the Slopes of Least-Squares Straight Lines (SLSSL) Fitted to the Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | -0.09 Average Z-Score | Standard Deviation 1.37 |
| Responders | Average of the Z-scores of the Slopes of Least-Squares Straight Lines (SLSSL) Fitted to the Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | 0.08 Average Z-Score | Standard Deviation 0.32 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.26990% CI: [-0.65, 0.3]t-test, 1 sided
Secondary
Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of biomarkers GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 through 6
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | -0.19 Average Z-Score | Standard Deviation 1.76 |
| Responders | Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | 0.08 Average Z-Score | Standard Deviation 0.2 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.21390% CI: [-0.83, 0.29]t-test, 1 sided
Secondary
Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of biomarkers GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 through 6
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | -0.08 Average Z-Score | Standard Deviation 1.4 |
| Responders | Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | 0.08 Average Z-Score | Standard Deviation 0.21 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.29390% CI: [-0.63, 0.32]t-test, 1 sided
Secondary
Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for biomarker analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 and 2
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | -0.24 Average Z-Score | Standard Deviation 1.71 |
| Responders | Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | 0.08 Average Z-Score | Standard Deviation 0.3 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.16890% CI: [-0.87, 0.23]t-test, 1 sided
Secondary
Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 12.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of biomarkers GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Week 1
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | 0.08 Average Z-Score | Standard Deviation 0.17 |
| Responders | Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | -0.10 Average Z-Score | Standard Deviation 0.47 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.07890% CI: [-0.03, 0.38]t-test, 1 sided
Secondary
Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 6.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of biomarkers GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual SLSSL divided by the overall SD. The average Z-scores of the SLSSL for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Week 1
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | 0.05 Average Z-Score | Standard Deviation 0.14 |
| Responders | Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | -0.10 Average Z-Score | Standard Deviation 0.49 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.07190% CI: [-0.02, 0.32]t-test, 1 sided
Secondary
Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA divided by the overall SD. The average of the Z-scores of the TWA for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 through 6
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | 0.49 Average Z-Score | Standard Deviation 1.75 |
| Responders | Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | -0.16 Average Z-Score | Standard Deviation 0.3 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.0390% CI: [0.09, 1.22]t-test, 1 sided
Secondary
Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA divided by the overall SD. The average of the Z-scores of the TWA for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 through 6
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | 0.27 Average Z-Score | Standard Deviation 1.53 |
| Responders | Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First 6 Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | -0.12 Average Z-Score | Standard Deviation 0.33 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.10990% CI: [-0.13, 0.91]t-test, 1 sided
Secondary
Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 12.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA divided by the overall SD. The average of the Z-scores of the TWA for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Week 1
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | 0.41 Average Z-Score | Standard Deviation 1.61 |
| Responders | Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | 0.01 Average Z-Score | Standard Deviation 1.06 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.15990% CI: [-0.27, 1.08]t-test, 1 sided
Secondary
Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 6.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA divided by the overall SD. The average of the Z-scores of the TWA for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Week 1
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | 0.25 Average Z-Score | Standard Deviation 1.4 |
| Responders | Average of the Z-scores of the TWA of Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | 0.04 Average Z-Score | Standard Deviation 1.2 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.28590% CI: [-0.41, 0.83]t-test, 1 sided
Secondary
Average of the Z-scores of the TWA of the CFB of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA CFB divided by the overall SD. The average of the Z-scores of the TWA CFB for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 and 2
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the TWA of the CFB of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | 0.10 Average Z-Score | Standard Deviation 0.3 |
| Responders | Average of the Z-scores of the TWA of the CFB of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 12. | -0.09 Average Z-Score | Standard Deviation 0.61 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.12790% CI: [-0.09, 0.46]t-test, 1 sided
Secondary
Average of the Z-scores of the TWA of the Changes From Baseline (CFB) of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6.
After enrollment blood was collected at baseline, twice per week for the first six weeks, then weekly through twelve weeks for analysis of GM and βDG. Clinical outcome was assessed for qualified participants at 6 and 12 weeks after initiation of antifungal treatment. For a given biomarker the Z-score is the difference from the mean of each individual TWA CFB divided by the overall SD. The average of the Z-scores of the TWA CFB for qualified participants is then calculated across all biomarkers, and used to derive the mean for R and NonR to antifungal therapy.
Time frame: Weeks 1 and 2
Population: Surviving participants with proven or probable IA at Day 14 post antifungal therapy, who had at least two valid results for each biomarker, and had a clinical outcome determined at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non-Responders | Average of the Z-scores of the TWA of the Changes From Baseline (CFB) of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | 0.07 Average Z-Score | Standard Deviation 0.26 |
| Responders | Average of the Z-scores of the TWA of the Changes From Baseline (CFB) of Fungal Biomarkers GM and βDG Over the First Two Weeks of Treatment for R and NonR to Anti-fungal Treatment at Week 6. | -0.12 Average Z-Score | Standard Deviation 0.69 |
Comparison: Mean Difference between Non-Responders and Respondersp-value: 0.10190% CI: [-0.06, 0.44]t-test, 1 sided