An Observational Study of Fungal Biomarkers (MK-0000-089 AM3)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00854607
First received: February 27, 2009
Last updated: September 12, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention
Aspergillosis
Other: No Intervention

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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. [ Time Frame: Weeks 1 and 2 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • 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. [ Time Frame: Weeks 1 and 2 ] [ Designated as safety issue: No ]
    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 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. [ Time Frame: Weeks 1 and 2 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Weeks 1 and 2 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Weeks 1 and 2 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Weeks 1 and 2 ] [ Designated as safety issue: No ]
    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 %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. [ Time Frame: Weeks 1 and 2 ] [ Designated as safety issue: No ]
    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 TWA of Fungal Biomarkers GM and βDG Over the First Week of Treatment for R and NonR to Anti-fungal Treatment at Week 6. [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    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 Week of Treatment for R and NonR to Anti-fungal Treatment at Week 12. [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    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 6. [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    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 12. [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Weeks 1 through 6 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Weeks 1 through 6 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Weeks 1 through 6 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Weeks 1 through 6 ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA

Blood samples are collected for 12 weeks to evaluate levels of fungal biomarkers.


Enrollment: 116
Study Start Date: March 2009
Study Completion Date: August 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Invasive Aspergillosis
Observational
Other: No Intervention
Blood samples will be collected for 12 weeks to evaluate levels of fungal biomarkers.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Participants will be selected through collaborations with clinicians.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00854607

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00854607     History of Changes
Other Study ID Numbers: MK-0000-089, 2009_553
Study First Received: February 27, 2009
Results First Received: July 24, 2012
Last Updated: September 12, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Aspergillosis
Mycoses

ClinicalTrials.gov processed this record on July 29, 2014