An Observational Study of Fungal Biomarkers (MK-0000-089)

Aspergillosis Clinical Trial

Official title:

A Prospective, Non-Intervention, Observational Assessment of the Correlation Between Circulating Biomarkers of Fungal Bioburden and Clinical Outcome in the Setting of Invasive Aspergillosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00854607
• Other study ID #: 0000-089
• Secondary ID: 2009_553
• Status: Completed
• Phase: N/A
• First received: February 27, 2009
• Last updated: August 4, 2015
• Start date: March 2009
• Est. completion date: August 2011

Study information

• Verified date: August 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: August 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Aspergillosis

Intervention

Other:
• No Intervention
Blood samples will be collected for 12 weeks to evaluate levels of fungal biomarkers.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Neofytos D, Railkar R, Mullane KM, Fredricks DN, Granwehr B, Marr KA, Almyroudis NG, Kontoyiannis DP, Maertens J, Fox R, Douglas C, Iannone R, Kauh E, Shire N. Correlation between Circulating Fungal Biomarkers and Clinical Outcome in Invasive Aspergillosi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average of the Z-scores of the Time-Weighted Averages (TWA) of Fungal Biomarkers Galactomannan (GM) and (1,3)-ß-D-glucan (ßDG) 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 ßDG. 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.	Weeks 1 and 2	No
Secondary	Average of the Z-scores of the Slopes of Least-Squares Straight Lines (SLSSL) Fitted to the Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Weeks 1 and 2	No
Secondary	Average of the Z-scores of the TWA of the Changes From Baseline (CFB) of Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Weeks 1 and 2	No
Secondary	Average of the Z-scores of the Percent Changes From Baseline (%CFB) of Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Weeks 1 and 2	No
Secondary	Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Weeks 1 and 2	No
Secondary	Average of the Z-scores of the TWA of the CFB of Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Weeks 1 and 2	No
Secondary	Average of the Z-scores of %CFB of Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Weeks 1 and 2	No
Secondary	Average of the Z-scores of the TWA of Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Week 1	No
Secondary	Average of the Z-scores of the TWA of Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Week 1	No
Secondary	Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Week 1	No
Secondary	Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Week 1	No
Secondary	Average of the Z-scores of the TWA of Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Weeks 1 through 6	No
Secondary	Average of the Z-scores of the TWA of Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Weeks 1 through 6	No
Secondary	Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Weeks 1 through 6	No
Secondary	Average of the Z-scores of the SLSSL Fitted to the Fungal Biomarkers GM and ßDG 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 ßDG. 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.	Weeks 1 through 6	No