The Relationship of Defeverscence and Itraconazole Plasma Level Study in Immunocompromised Participants
- Registration Number
- NCT01021683
- Lead Sponsor
- Janssen Korea, Ltd., Korea
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 203
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Itraconazole 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Plasma Level of Itraconazole at 1000 Nanogram Per Milliliter (ng/mL) or Higher After Administration of Study Treatment Day 5 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
Name Time Method Absolute Neutrophil Count (ANC) Baseline (Day 0) The mean values for ANC based on blood tests performed on Day 0 (before starting the study treatment) constitute a Baseline measure for ANC.
Plasma Concentration of Itraconazole by Breakthrough Fungal Infection Day 5 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.
Mean Time to Defervescence in Participants Who Received the Study Treatment Day 0 up to Day 14 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.
Plasma Concentration of Itraconazole by Overall Success Rate (OSR) in Participants Who Received the Study Treatment Day 5 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 Deferevescence After Administration of Study Treatment Day 0 up to Day 14 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.
Percentage of Participants With Defervescence by Plasma Level of Itraconazole Day 5 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.
Percentage of Participants With Baseline Fungal Infection Baseline (Day 0) 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.
Duration of Neutropenia Day 0 up to Day 14 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.