The Relationship of Defeverscence and Itraconazole Plasma Level Study in Immunocompromised Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Korea, Ltd., Korea
ClinicalTrials.gov Identifier:
NCT01021683
First received: November 25, 2009
Last updated: July 24, 2013
Last verified: July 2013
  Purpose

The purpose of this observational study is to investigate whether a sufficient concentration of itraconazole can influence disappearance of a fever (defeverscence) when intravenous (into the vein) itraconazole is administered for resolving unknown neutropenic fever of participants who are given itraconazole oral solution as a prophylaxis under general treatment conditions.


Condition Intervention Phase
Hematologic Neoplasms
Neutropenia
Fever
Drug: Itraconazole
Phase 4

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: The Relationship of Defeverscence and Itraconazole Plasma Level Using Sporanox IV as an Empiric Therapy in Immunocompromised Patients Who Have Been Treated With Sporanox Oral Solution as Prophylaxis

Resource links provided by NLM:


Further study details as provided by Janssen Korea, Ltd., Korea:

Primary Outcome Measures:
  • Percentage of Participants Achieving Plasma Level of Itraconazole at 1000 Nanogram Per Milliliter (ng/mL) or Higher After Administration of Study Treatment [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Percentage of participants who achieved more than or equal to 1000 ng/ml level after administration of study treatment were reported. Plasma level of itraconazole was defined as the sum of itraconazole concentration (IC) and hydroxyitraconazole concentration (HIC).


Secondary Outcome Measures:
  • Percentage of Participants With Deferevescence After Administration of Study Treatment [ Time Frame: Day 0 up to Day 14 ] [ Designated as safety issue: No ]
    Defervescence was defined as fall of the body temperature below 38.0 degree Celsius (C) at least once after starting to receive the study treatment.

  • Mean Time to Defervescence in Participants Who Received the Study Treatment [ Time Frame: Day 0 up to Day 14 ] [ Designated as safety issue: No ]
    The mean time to defervescence was reported in participants who received the study treatment. Defervescence was defined as fall of the body temperature below 38.0 degree C at least once after starting to receive the study treatment.

  • Duration of Neutropenia [ Time Frame: Day 0 up to Day 14 ] [ Designated as safety issue: No ]
    The duration of neutropenia was reported. Neutropenia was defined as neutrophil count less than or equal to (<=) 500 cells per cubic millimeter (cells/mm^3), or neutrophil count <=1000 cells/mm^3 and anticipated to decrease to <=500 cells/mm^3 within several days.

  • Absolute Neutrophil Count (ANC) [ Time Frame: Baseline (Day 0) ] [ Designated as safety issue: No ]
    The mean values for ANC based on blood tests performed on Day 0 (before starting the study treatment) constitute a Baseline measure for ANC.

  • Percentage of Participants With Defervescence by Plasma Level of Itraconazole [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Defervescence was defined as fall of the body temperature below 38.0 degree C at least once after starting to receive the study treatment. Plasma level of itraconazole was defined as the sum of IC and HIC.

  • Plasma Concentration of Itraconazole by Overall Success Rate (OSR) in Participants Who Received the Study Treatment [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Plasma level of itraconazole was defined as the sum of IC and HIC. The OSR was defined based on satisfaction of the following criteria: (1) participants if treated for baseline fungal infection, there was either eradication (removal of fungus in culture), or presumed eradication; no evidence in culture but appeared to be treated clinically, (2) absence of breakthrough fungal infection during the treatment and for 7 days after completing the treatment, (3) survival for 7 days after completing the treatment, (4) absence of early withdrawal due to adverse events or lack of efficacy, and (5) defervescence. The presence and absence of OS was reported.

  • Percentage of Participants With Baseline Fungal Infection [ Time Frame: Baseline (Day 0) ] [ Designated as safety issue: No ]
    Blood cultures (a laboratory test on a sample of blood) were assessed to identify fungus. Percentage of participants with presence or absence of fungus before starting the study drug were calculated.

  • Plasma Concentration of Itraconazole by Breakthrough Fungal Infection [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Plasma level of itraconazole was defined as the sum of IC and HIC. A breakthrough fungal infection was defined as any fungal infection that was diagnosed more than (>) 3 days on or during therapy or within 7 days after completion of therapy. Blood cultures were assessed to identify fungus.


Biospecimen Retention:   Samples Without DNA

Blood cultures


Enrollment: 203
Study Start Date: July 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Itraconazole
Participants who have been receiving itraconazole will be observed prospectively. Itraconazole will be administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, followed by itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia is recovered.
Drug: Itraconazole
Itraconazole will be administered as an infusion (a fluid or a medicine delivered into a vein by way of a needle) over one hour at the dose of 200 milligram (mg) per dose twice daily for 2 days, followed by 200 mg once daily for 12 days, followed by itraconazole oral solution at the dose of 200 mg per dose twice daily for 14 days until clinically significant neutropenia is recovered.

Detailed Description:

This is a prospective (study following patients forward in time), open-label (all people know the identity of the intervention), multi-center (conducted in more than one center) observational study to examine the correlation between a sufficient blood concentration of itraconazole and disappearance of a fever (defeverscence) when itraconazole injection is administered for resolving unknown neutropenic fever of participants who are given itraconazole oral solution as a prophylaxis under general treatment conditions. The recommended dose of the drug will be 200 milligram (mg), which will be administered intravenously, twice daily for 2 days (a total of 4 doses) and then 200 mg once daily for 12 days. After the administration for a total of 14 days, itraconazole oral solution 200 mg (which is equivalent to 20 ml) twice daily will be continued for a total of 14 days until clinically significant neutropenia is resolved.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Immunocompromized participants with neutropenic fever who have been treated with itraconazole oral solution as prophylaxis and eligible for intravenous (into the vein) itraconazole in accordance with the local label.

Criteria

Inclusion Criteria:

  • Immunocompromised participants with neutropenic fever who have been treated with itraconazole oral solution as prophylaxis
  • Female participants who are postmenopausal or received contraceptive operation or refrain from sexual relations and women of childbearing potential should conduct an effective method of birth control (oral contraceptives, injections, intrauterine device, double barrier method, contraceptive patch and male partner's sterilization) before participation and during the study
  • Male participants who will not have a baby within 2 months after the completion of itraconazole therapy

Exclusion Criteria:

  • Fever due to documented deep-seated fungal infection at the entry into the study, but documented candidemia will be included
  • Participants with kidney function related abnormalities with calculated creatinine clearance of 30 milliliter per minute (mL/min) or lower
  • Aminotransferase level 5 times or higher of normal limit and total bilirubin level 5 milliliter per deciliter (mL/dL) or higher due to hepatic dysfunction
  • Participants with dementia (mental decline) related to head injury and hypoxic brain injury
  • Participants with mental illness which may interfere with cooperation in treatment and monitoring condition of the clinical study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01021683

Sponsors and Collaborators
Janssen Korea, Ltd., Korea
Investigators
Study Director: Janssen Korea, Ltd., Korea Clinical Trial Janssen Korea, Ltd., Korea
  More Information

No publications provided

Responsible Party: Janssen Korea, Ltd., Korea
ClinicalTrials.gov Identifier: NCT01021683     History of Changes
Other Study ID Numbers: CR016597, ITR-KOR-5085, ITRFUN4049
Study First Received: November 25, 2009
Results First Received: April 15, 2013
Last Updated: July 24, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Janssen Korea, Ltd., Korea:
Hematological neoplasms
Neutropenia
Fever
Itraconazole
Sporanox
Antifungal prophylaxis
Defeverscence

Additional relevant MeSH terms:
Neoplasms
Fever
Neutropenia
Hematologic Neoplasms
Body Temperature Changes
Signs and Symptoms
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Neoplasms by Site
Itraconazole
Hydroxyitraconazole
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 21, 2014