<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03260634</url>
  </required_header>
  <id_info>
    <org_study_id>496-59</org_study_id>
    <nct_id>NCT03260634</nct_id>
  </id_info>
  <brief_title>The Study of Voriconazole Trough Level in the First Two Weeks After Administration in King Chulalongkorn Memorial Hospital.</brief_title>
  <official_title>The Study of Voriconazole Trough Level in the First Two Weeks After Administration in King Chulalongkorn Memorial Hospital.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chulalongkorn University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chulalongkorn University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Invasive fungal infections are a significant cause of morbidity and mortality in&#xD;
      immunocompromised host such as prolong neutropenic patients , post transplantation patients,&#xD;
      malignancies or advanced AIDS . The majority of these infections were caused by Aspergillus&#xD;
      species, which the first line of treatment is antifungal agent, Voriconazole , a triazole&#xD;
      antifungal drug which was approved by the Food and Drug Administration in May 2002 for the&#xD;
      treatment of invasive aspergillosis and refractory infections of Scedosporium apiospermum and&#xD;
      Fusarium spp. There are two forms of Voriconazole , oral and intravenous form. The&#xD;
      recommendation dose is 6 mg/kg twice daily for two dosages, followed by 4 mg/kg twice daily&#xD;
      in intravenous form or a loading dose of 400 mg twice daily for two doses is used (for&#xD;
      individuals &gt;40 kg), followed by 200 mg twice daily, and in individuals &lt;40 kg the&#xD;
      maintenance dose is 100 mg twice daily in oral form.&#xD;
&#xD;
      Voriconazole has a narrow therapeutic window and nonlinear pharmacokinetic profile with wide&#xD;
      inter-individual and intra-individual variability, such as age, race, genotypic variation,&#xD;
      liver dysfunction, the presence of food and drug-drug interactions with CYP450 inhibitors.&#xD;
      These large variations in pharmacokinetics may be associated with decreased efficacy or&#xD;
      increased toxicity. Therefore , monitoring of serum trough concentrations is recommended in&#xD;
      the following infections: invasive aspergillosis treatment , endophthalmitis; meningitis or&#xD;
      osteoarticular infections due to Exserohilum rostratum.&#xD;
&#xD;
      In Thai population , there are different genetic polymorphism from Caucasian ,resulting in a&#xD;
      different response to the initial dose and there is limited resources in Thailand , mostly&#xD;
      patients are unaccessible for Voriconazole level. Especially,in the period of starting drug,&#xD;
      which is the critical period for patients ,most of them are post chemotherapy which may have&#xD;
      gastrointestinal problems, mucositis , vomiting or diarrhea ,as well as receiving multiple&#xD;
      concurrent medications. All of these affect drug absorption,drug level and efficacy of&#xD;
      treatment. Thus, this study was designed to evaluated Voriconazole level in Thai patients in&#xD;
      the first two week after administration.&#xD;
&#xD;
      Primary question&#xD;
&#xD;
        -  From the first collected of Voriconazole drug level , Are the invasive fungal infection&#xD;
           patients in King Chulalongkorn Memorial Hospital achieved the drug level more than 60% ?&#xD;
&#xD;
      Secondary question&#xD;
&#xD;
        -  Which factor affecting Voriconazole through level in the first two weeks after&#xD;
           administration?&#xD;
&#xD;
      Research Design&#xD;
&#xD;
        -  Observational Studies (Descriptive retrospective and prospective study)&#xD;
&#xD;
      Research Methodology&#xD;
&#xD;
      Target Population&#xD;
&#xD;
        -  Patients received Voriconazole for treatment or prophylaxis invasive fungal infection&#xD;
&#xD;
      Study population&#xD;
&#xD;
        -  Patients in King Chulalongkorn Memorial hospital received Voriconazole for treatment or&#xD;
           prophylaxis invasive fungal infection&#xD;
&#xD;
      Sample size&#xD;
&#xD;
      n= ZZ/2P(1-P) /dd&#xD;
&#xD;
        -  n = sample size&#xD;
&#xD;
        -  P =Incident rate&#xD;
&#xD;
        -  From the pilot study of 15 Invasive fungal infection patients in King Chulalongkorn&#xD;
           memorial hospital from February to September 2015 , 60% ( 9 of 15 patients) of the first&#xD;
           collected of Voriconazole trough level achieved the therapeutic level.&#xD;
&#xD;
      replaced P = 0.6&#xD;
&#xD;
        -  Z = 95% confident interval = 1.96&#xD;
&#xD;
        -  d = acceptable error = 0.10&#xD;
&#xD;
      n = (1.96) (1.96) (0.60)(1-0.60) / (0.10)(0.10)&#xD;
&#xD;
      n =92 , sample size = 92&#xD;
&#xD;
      Study processing and data collection&#xD;
&#xD;
      Data collection&#xD;
&#xD;
        -  Collected data of patients received Voriconazole in first two weeks of treatment or&#xD;
           prophylaxis invasive fungal infection in King Chulalongkorn Memorial hospital in&#xD;
           2015-2017 from outpatient records , inpatient records and computer database in King&#xD;
           Chulalongkorn Memorial hospital. This data included&#xD;
&#xD;
        -  Baseline characteristics : sex, age ,weight ,BMI ,co-morbid ,personal history of smoking&#xD;
           or alcohol drinking&#xD;
&#xD;
        -  Basic laboratory investigation : complete blood count , Creatinin , liver function test&#xD;
           , albumin level&#xD;
&#xD;
        -  Gastrointestinal problems&#xD;
&#xD;
        -  Indication of Voriconazole treatment&#xD;
&#xD;
        -  Data of invasive fungal infection :&#xD;
&#xD;
        -  Data of Voriconazole usage : Loading dose, Maintenance dose, Trough level , Data of drug&#xD;
           adjustment, Concurrent medication used, Side effect&#xD;
&#xD;
        -  All data was summarized and recorded in case report forms.&#xD;
&#xD;
      Data Analysis and Statistics&#xD;
&#xD;
      The data was analysed by computer using SPSS17 program This study used descriptive statistics&#xD;
      ,describing general information, age, results, laboratory results and side effects of the&#xD;
      drug in mean ,percentage or standard deviation. And used the chi-square test for analysis of&#xD;
      the proportion of patients with serum drug levels within the therapeutic range.&#xD;
&#xD;
      This study used a confidence level of 95%, p-value less than 0.05 was statistically&#xD;
      significant.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 1, 2016</start_date>
  <completion_date type="Anticipated">January 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of patients achieved therapeutic level of voriconazole in the first two weeks after administration</measure>
    <time_frame>2015-2017</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Factors have significant impact to voriconazole through level .</measure>
    <time_frame>2015-2017</time_frame>
    <description>Factors that have significant impact to voriconazole through level will be assess in this study such as drug interaction , oral mucositis .</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">92</enrollment>
  <condition>Voriconazole</condition>
  <condition>Fungal Infection</condition>
  <arm_group>
    <arm_group_label>Voriconazole</arm_group_label>
    <description>Patient was received voriconazole according to individual indication. The starting dose is 6 mg/kg iv twice daily for two dosages, followed by 4 mg/kg iv twice daily in intravenous form or a loading dose of 400 mg twice daily for two doses is used (for individuals &gt;40 kg), followed by 200 mg twice daily, and in individuals &lt;40 kg the maintenance dose is 100 mg twice daily in oral form.&#xD;
The dosage was adjusted by drug level and toxicity. The duration of drug used was depended on indication of treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Voriconazole</intervention_name>
    <arm_group_label>Voriconazole</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Thai patient in King Chulalongkorn Memorial Hospital ,Bangkok , Thailand, age between 18&#xD;
        and 80 year olds ,receiving Voriconazole for treatment or prophylaxis invasive fungal&#xD;
        infection , between 2015-2017.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Thai patient in King Chulalongkorn Memorial Hospital , age between 18 and 80 years old&#xD;
&#xD;
          -  Receiving Voriconazole for treatment or prophylaxis invasive fungal infection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe hepatic or renal dysfunction&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Presence of history of allergy to any Azole antifungal agents&#xD;
&#xD;
          -  Death within 2 weeks after treatment of invasive fungal infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Chulalongkorn university</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <reference>
    <citation>Hamada Y, Tokimatsu I, Mikamo H, Kimura M, Seki M, Takakura S, Ohmagari N, Takahashi Y, Kasahara K, Matsumoto K, Okada K, Igarashi M, Kobayashi M, Mochizuki T, Nishi Y, Tanigawara Y, Kimura T, Takesue Y. Practice guidelines for therapeutic drug monitoring of voriconazole: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. J Infect Chemother. 2013 Jun;19(3):381-92. doi: 10.1007/s10156-013-0607-8. Epub 2013 May 15. No abstract available.</citation>
    <PMID>23673473</PMID>
  </reference>
  <reference>
    <citation>Park WB, Kim NH, Kim KH, Lee SH, Nam WS, Yoon SH, Song KH, Choe PG, Kim NJ, Jang IJ, Oh MD, Yu KS. The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial. Clin Infect Dis. 2012 Oct;55(8):1080-7. doi: 10.1093/cid/cis599. Epub 2012 Jul 3.</citation>
    <PMID>22761409</PMID>
  </reference>
  <reference>
    <citation>Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis. 2008 Jan 15;46(2):201-11. doi: 10.1086/524669.</citation>
    <PMID>18171251</PMID>
  </reference>
  <reference>
    <citation>Tan K, Brayshaw N, Tomaszewski K, Troke P, Wood N. Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities. J Clin Pharmacol. 2006 Feb;46(2):235-43. doi: 10.1177/0091270005283837.</citation>
    <PMID>16432276</PMID>
  </reference>
  <reference>
    <citation>Ueda K, Nannya Y, Kumano K, Hangaishi A, Takahashi T, Imai Y, Kurokawa M. Monitoring trough concentration of voriconazole is important to ensure successful antifungal therapy and to avoid hepatic damage in patients with hematological disorders. Int J Hematol. 2009 Jun;89(5):592-9. doi: 10.1007/s12185-009-0296-3. Epub 2009 Apr 2.</citation>
    <PMID>19340528</PMID>
  </reference>
  <reference>
    <citation>Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Nguyen MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young JA, Bennett JE. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60. doi: 10.1093/cid/ciw326. Epub 2016 Jun 29.</citation>
    <PMID>27365388</PMID>
  </reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>August 21, 2017</last_update_submitted>
  <last_update_submitted_qc>August 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>voriconazole</keyword>
  <keyword>therapeutic drug monitoring</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycoses</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Voriconazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03260634
org study id: 496-59
nct id: NCT03260634
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Invasive fungal infections are a significant cause of morbidity and mortality in
      immunocompromised host such as prolong neutropenic patients , post transplantation patients,
      malignancies or advanced AIDS . The majority of these infections were caused by Aspergillus
      species, which the first line of treatment is antifungal agent, Voriconazole , a triazole
      antifungal drug which was approved by the Food and Drug Administration in May 2002 for the
      treatment of invasive aspergillosis and refractory infections of Scedosporium apiospermum and
      Fusarium spp. There are two forms of Voriconazole , oral and intravenous form. The
      recommendation dose is 6 mg/kg twice daily for two dosages, followed by 4 mg/kg twice daily
      in intravenous form or a loading dose of 400 mg twice daily for two doses is used (for
      individuals >40 kg), followed by 200 mg twice daily, and in individuals <40 kg the
      maintenance dose is 100 mg twice daily in oral form.

      Voriconazole has a narrow therapeutic window and nonlinear pharmacokinetic profile with wide
      inter-individual and intra-individual variability, such as age, race, genotypic variation,
      liver dysfunction, the presence of food and drug-drug interactions with CYP450 inhibitors.
      These large variations in pharmacokinetics may be associated with decreased efficacy or
      increased toxicity. Therefore , monitoring of serum trough concentrations is recommended in
      the following infections: invasive aspergillosis treatment , endophthalmitis; meningitis or
      osteoarticular infections due to Exserohilum rostratum.

      In Thai population , there are different genetic polymorphism from Caucasian ,resulting in a
      different response to the initial dose and there is limited resources in Thailand , mostly
      patients are unaccessible for Voriconazole level. Especially,in the period of starting drug,
      which is the critical period for patients ,most of them are post chemotherapy which may have
      gastrointestinal problems, mucositis , vomiting or diarrhea ,as well as receiving multiple
      concurrent medications. All of these affect drug absorption,drug level and efficacy of
      treatment. Thus, this study was designed to evaluated Voriconazole level in Thai patients in
      the first two week after administration.

      Primary question

        -  From the first collected of Voriconazole drug level , Are the invasive fungal infection
           patients in King Chulalongkorn Memorial Hospital achieved the drug level more than 60% ?

      Secondary question

        -  Which factor affecting Voriconazole through level in the first two weeks after
           administration?

      Research Design

        -  Observational Studies (Descriptive retrospective and prospective study)

      Research Methodology

      Target Population

        -  Patients received Voriconazole for treatment or prophylaxis invasive fungal infection

      Study population

        -  Patients in King Chulalongkorn Memorial hospital received Voriconazole for treatment or
           prophylaxis invasive fungal infection

      Sample size

      n= ZZ/2P(1-P) /dd

        -  n = sample size

        -  P =Incident rate

        -  From the pilot study of 15 Invasive fungal infection patients in King Chulalongkorn
           memorial hospital from February to September 2015 , 60% ( 9 of 15 patients) of the first
           collected of Voriconazole trough level achieved the therapeutic level.

      replaced P = 0.6

        -  Z = 95% confident interval = 1.96

        -  d = acceptable error = 0.10

      n = (1.96) (1.96) (0.60)(1-0.60) / (0.10)(0.10)

      n =92 , sample size = 92

      Study processing and data collection

      Data collection

        -  Collected data of patients received Voriconazole in first two weeks of treatment or
           prophylaxis invasive fungal infection in King Chulalongkorn Memorial hospital in
           2015-2017 from outpatient records , inpatient records and computer database in King
           Chulalongkorn Memorial hospital. This data included

        -  Baseline characteristics : sex, age ,weight ,BMI ,co-morbid ,personal history of smoking
           or alcohol drinking

        -  Basic laboratory investigation : complete blood count , Creatinin , liver function test
           , albumin level

        -  Gastrointestinal problems

        -  Indication of Voriconazole treatment

        -  Data of invasive fungal infection :

        -  Data of Voriconazole usage : Loading dose, Maintenance dose, Trough level , Data of drug
           adjustment, Concurrent medication used, Side effect

        -  All data was summarized and recorded in case report forms.

      Data Analysis and Statistics

      The data was analysed by computer using SPSS17 program This study used descriptive statistics
      ,describing general information, age, results, laboratory results and side effects of the
      drug in mean ,percentage or standard deviation. And used the chi-square test for analysis of
      the proportion of patients with serum drug levels within the therapeutic range.

      This study used a confidence level of 95%, p-value less than 0.05 was statistically
      significant.
observational model: Other
time perspective: Other
measure: Percentage of patients achieved therapeutic level of voriconazole in the first two weeks after administration
time frame: 2015-2017
measure: Factors have significant impact to voriconazole through level .
time frame: 2015-2017
description: Factors that have significant impact to voriconazole through level will be assess in this study such as drug interaction , oral mucositis .
arm group label: Voriconazole
description: Patient was received voriconazole according to individual indication. The starting dose is 6 mg/kg iv twice daily for two dosages, followed by 4 mg/kg iv twice daily in intravenous form or a loading dose of 400 mg twice daily for two doses is used (for individuals >40 kg), followed by 200 mg twice daily, and in individuals <40 kg the maintenance dose is 100 mg twice daily in oral form.
The dosage was adjusted by drug level and toxicity. The duration of drug used was depended on indication of treatment.
intervention type: Drug
intervention name: Voriconazole
arm group label: Voriconazole
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Thailand
citation: Hamada Y, Tokimatsu I, Mikamo H, Kimura M, Seki M, Takakura S, Ohmagari N, Takahashi Y, Kasahara K, Matsumoto K, Okada K, Igarashi M, Kobayashi M, Mochizuki T, Nishi Y, Tanigawara Y, Kimura T, Takesue Y. Practice guidelines for therapeutic drug monitoring of voriconazole: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. J Infect Chemother. 2013 Jun;19(3):381-92. doi: 10.1007/s10156-013-0607-8. Epub 2013 May 15. No abstract available.
PMID: 23673473
citation: Park WB, Kim NH, Kim KH, Lee SH, Nam WS, Yoon SH, Song KH, Choe PG, Kim NJ, Jang IJ, Oh MD, Yu KS. The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial. Clin Infect Dis. 2012 Oct;55(8):1080-7. doi: 10.1093/cid/cis599. Epub 2012 Jul 3.
PMID: 22761409
citation: Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis. 2008 Jan 15;46(2):201-11. doi: 10.1086/524669.
PMID: 18171251
citation: Tan K, Brayshaw N, Tomaszewski K, Troke P, Wood N. Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities. J Clin Pharmacol. 2006 Feb;46(2):235-43. doi: 10.1177/0091270005283837.
PMID: 16432276
citation: Ueda K, Nannya Y, Kumano K, Hangaishi A, Takahashi T, Imai Y, Kurokawa M. Monitoring trough concentration of voriconazole is important to ensure successful antifungal therapy and to avoid hepatic damage in patients with hematological disorders. Int J Hematol. 2009 Jun;89(5):592-9. doi: 10.1007/s12185-009-0296-3. Epub 2009 Apr 2.
PMID: 19340528
citation: Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Nguyen MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young JA, Bennett JE. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60. doi: 10.1093/cid/ciw326. Epub 2016 Jun 29.
PMID: 27365388
responsible party type: Sponsor
mesh term: Mycoses
mesh term: Voriconazole
sharing ipd: No