Trial Outcomes & Findings for An Observational Study of Fungal Biomarkers (MK-0000-089) (NCT NCT00854607)
NCT ID: NCT00854607
Last Updated: 2015-08-21
Results Overview
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.
COMPLETED
116 participants
Weeks 1 and 2
2015-08-21
Participant Flow
Participant milestones
| Measure |
Invasive Aspergillosis
Participants who enrolled with a presumptive diagnosis of possible, probable or proven Invasive Aspergillosis (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
|
|---|---|
|
Enrollment
STARTED
|
116
|
|
Enrollment
COMPLETED
|
116
|
|
Enrollment
NOT COMPLETED
|
0
|
|
2 Weeks After Start Anti-fungal Therapy
STARTED
|
116
|
|
2 Weeks After Start Anti-fungal Therapy
COMPLETED
|
51
|
|
2 Weeks After Start Anti-fungal Therapy
NOT COMPLETED
|
65
|
Reasons for withdrawal
| Measure |
Invasive Aspergillosis
Participants who enrolled with a presumptive diagnosis of possible, probable or proven Invasive Aspergillosis (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
|
|---|---|
|
2 Weeks After Start Anti-fungal Therapy
Diagnosed with Possible IA
|
65
|
Baseline Characteristics
An Observational Study of Fungal Biomarkers (MK-0000-089)
Baseline characteristics by cohort
| Measure |
Invasive Aspergillosis
n=51 Participants
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
|
|---|---|
|
Age, Continuous
|
56.9 years
STANDARD_DEVIATION 13.3 • n=39 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Weeks 1 and 2Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
-0.09 Average Z-Score
Standard Deviation 0.61
|
SECONDARY outcome
Timeframe: Weeks 1 and 2Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
0.08 Average Z-Score
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: Weeks 1 and 2Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
-0.12 Average Z-Score
Standard Deviation 0.69
|
SECONDARY outcome
Timeframe: Weeks 1 and 2Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
-0.00 Average Z-Score
Standard Deviation 0.79
|
SECONDARY outcome
Timeframe: Weeks 1 and 2Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=16 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=28 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
0.08 Average Z-Score
Standard Deviation 0.30
|
SECONDARY outcome
Timeframe: Weeks 1 and 2Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=16 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=28 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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 0.30
|
-0.09 Average Z-Score
Standard Deviation 0.61
|
SECONDARY outcome
Timeframe: Weeks 1 and 2Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=16 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=28 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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 1.40
|
-0.16 Average Z-Score
Standard Deviation 0.46
|
SECONDARY outcome
Timeframe: Week 1Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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 1.40
|
0.04 Average Z-Score
Standard Deviation 1.20
|
SECONDARY outcome
Timeframe: Week 1Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=16 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=28 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
0.01 Average Z-Score
Standard Deviation 1.06
|
SECONDARY outcome
Timeframe: Week 1Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
-0.10 Average Z-Score
Standard Deviation 0.49
|
SECONDARY outcome
Timeframe: Week 1Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=16 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=28 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
-0.10 Average Z-Score
Standard Deviation 0.47
|
SECONDARY outcome
Timeframe: Weeks 1 through 6Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
-0.12 Average Z-Score
Standard Deviation 0.33
|
SECONDARY outcome
Timeframe: Weeks 1 through 6Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=16 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=28 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
-0.16 Average Z-Score
Standard Deviation 0.30
|
SECONDARY outcome
Timeframe: Weeks 1 through 6Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=25 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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 1.40
|
0.08 Average Z-Score
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: Weeks 1 through 6Population: 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.
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.
Outcome measures
| Measure |
Non-Responders
n=16 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Non-Responders at Week 6.
|
Responders
n=28 Participants
Participants started on standard of care anti-fungal therapy on Day 0 who were diagnosed as Responders at Week 6.
|
|---|---|---|
|
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
|
0.08 Average Z-Score
Standard Deviation 0.20
|
Adverse Events
Invasive Aspergillosis
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Results disclosure agreements
- Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
- Publication restrictions are in place
Restriction type: OTHER