Effect of Inflammation on Pharmacokinetics of Posaconazole

Sponsor
University Medical Center Groningen (Other)
Overall Status
Completed
CT.gov ID
NCT02492802
Collaborator
(none)
64
1
23.6
2.7

Study Details

Study Description

Brief Summary

Posaconazole plasma concentration and inflammatory markers will be determined in all samples available from routine analysis.

Condition or Disease Intervention/Treatment Phase

Detailed Description

A prospective observational study will be performed at the University Medical Center Groningen, the Netherlands using longitudinal data collection. The design of the study will be that patients starting on posaconazole treatment will be evaluated. After informed consent is obtained medical data will be collected from the medical chart. Posaconazole plasma concentration (trough levels) and inflammatory markers (e.g. C-reactive protein) will be determined in all samples available from routine analysis (often daily). This will result in a detailed data set capturing day to day variations in inflammation and drug concentrations.

Study Design

Study Type:
Observational
Actual Enrollment :
64 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Effect of Inflammation on Pharmacokinetics of Posaconazole
Actual Study Start Date :
Aug 13, 2015
Actual Primary Completion Date :
Jun 1, 2017
Actual Study Completion Date :
Aug 1, 2017

Arms and Interventions

Arm Intervention/Treatment
posaconazole-group

patients receiving posaconazole for prophylaxis or treatment of invasive fungal infection

Drug: posaconazole
collection plasma samples for measuring posaconazole drug concentration
Other Names:
  • noxafil
  • Outcome Measures

    Primary Outcome Measures

    1. C Reactive Protein Levels in mg/L (CRP) on Posaconazole Concentrations in mg/L [6 months after start of treatment]

      Posaconazole drug exposure during treatment in different stages of inflammation. To determine the differences in concentrations between patients a random additive effect was used. Additionally, to correct for differences in intervals between observations a first-order autoregressive correlation was used. The Wald type III test was used to assess the influence of inflammation on posaconazole concentration.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 18 yrs

    • receiving posaconazole

    • Written informed consent

    Exclusion Criteria:
    • none

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Medical Center Groningen Groningen Netherlands 9700 RB

    Sponsors and Collaborators

    • University Medical Center Groningen

    Investigators

    • Principal Investigator: Jan-Willem Alffenaar, PharmD, PhD, UMCG

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Jan-Willem C Alffenaar, PharmD PhD, University Medical Center Groningen
    ClinicalTrials.gov Identifier:
    NCT02492802
    Other Study ID Numbers:
    • POSA-CRP
    First Posted:
    Jul 9, 2015
    Last Update Posted:
    Aug 6, 2019
    Last Verified:
    Jul 1, 2019
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Patients on Posaconazole
    Arm/Group Description Hematology patients receiving posaconazole for routine care.
    Period Title: Overall Study
    STARTED 64
    COMPLETED 64
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Patients on Posaconazole
    Arm/Group Description Patient characteristics and drug dosing information (oral and intravenous dosing, daily dose of posaconazole)
    Overall Participants 64
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    62
    Sex: Female, Male (Count of Participants)
    Female
    23
    35.9%
    Male
    41
    64.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    0
    0%
    More than one race
    0
    0%
    Unknown or Not Reported
    64
    100%
    Weight (kg) (kg) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [kg]
    79
    Height (cm) (cm) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [cm]
    178
    Acute myeloid leukemia (Count of Participants)
    Count of Participants [Participants]
    40
    62.5%
    Myelodysplastic syndrome (Count of Participants)
    Count of Participants [Participants]
    10
    15.6%
    Other underlying disease (Count of Participants)
    Count of Participants [Participants]
    14
    21.9%
    Allogeneic stem cell transplant (Count of Participants)
    Count of Participants [Participants]
    22
    34.4%
    Autologous stem cell transplant (Count of Participants)
    Count of Participants [Participants]
    2
    3.1%
    No stem cell transplant received (Count of Participants)
    Count of Participants [Participants]
    39
    60.9%
    Oral posaconazole (Count of Participants)
    Count of Participants [Participants]
    59
    92.2%
    Intravenous and oral posaconazole (Count of Participants)
    Count of Participants [Participants]
    5
    7.8%
    Daily dose of posaconazole (mg/kg) (mg/kg) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/kg]
    4.5
    Both stem cell transplantations received (Count of Participants)
    Count of Participants [Participants]
    1
    1.6%

    Outcome Measures

    1. Primary Outcome
    Title C Reactive Protein Levels in mg/L (CRP) on Posaconazole Concentrations in mg/L
    Description Posaconazole drug exposure during treatment in different stages of inflammation. To determine the differences in concentrations between patients a random additive effect was used. Additionally, to correct for differences in intervals between observations a first-order autoregressive correlation was used. The Wald type III test was used to assess the influence of inflammation on posaconazole concentration.
    Time Frame 6 months after start of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Posaconazole
    Arm/Group Description Patients who received posaconazole for routine care
    Measure Participants 64
    Posaconazole concentration
    1.8
    C reactive protein
    23.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Posaconazole
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.77
    Comments
    Method The Wald Type III test
    Comments

    Adverse Events

    Time Frame Adverse events (AEs) were evaluated from the start of the treatment up to 1 year.
    Adverse Event Reporting Description Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
    Arm/Group Title Posaconazole
    Arm/Group Description Route of administration: Oral (MDR tablet), intravenous (infusion) Daily dose (mg/kg body weight): 3.75 (3.4-4.9)
    All Cause Mortality
    Posaconazole
    Affected / at Risk (%) # Events
    Total 5/64 (7.8%)
    Serious Adverse Events
    Posaconazole
    Affected / at Risk (%) # Events
    Total 0/64 (0%)
    Other (Not Including Serious) Adverse Events
    Posaconazole
    Affected / at Risk (%) # Events
    Total 3/64 (4.7%)
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders 1/64 (1.6%) 1
    Blood and lymphatic system disorders 1/64 (1.6%) 1
    Hepatobiliary disorders
    Hepatobiliary disorders 1/64 (1.6%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Jan-Willem Alffenaar, PhD
    Organization University Medical Center Groningen
    Phone +31503614035
    Email j.w.c.alffenaar@umcg.nl
    Responsible Party:
    Jan-Willem C Alffenaar, PharmD PhD, University Medical Center Groningen
    ClinicalTrials.gov Identifier:
    NCT02492802
    Other Study ID Numbers:
    • POSA-CRP
    First Posted:
    Jul 9, 2015
    Last Update Posted:
    Aug 6, 2019
    Last Verified:
    Jul 1, 2019