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

Fever Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01021683
• Other study ID #: CR016597
• Secondary ID: ITR-KOR-5085ITRF
• Status: Completed
• Phase: Phase 4
• First received: November 25, 2009
• Last updated: July 24, 2013
• Start date: July 2009
• Est. completion date: July 2010

Study information

• Verified date: July 2013
• Source: Janssen Korea, Ltd., Korea
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Fever
• Hematologic Neoplasms
• Neutropenia

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Korea, Ltd., Korea

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Plasma Level of Itraconazole at 1000 Nanogram Per Milliliter (ng/mL) or Higher After Administration of Study Treatment	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).	Day 5	No
Secondary	Percentage of Participants With Deferevescence After Administration of Study Treatment	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.	Day 0 up to Day 14	No
Secondary	Mean Time to Defervescence in Participants Who Received the Study Treatment	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.	Day 0 up to Day 14	No
Secondary	Duration of Neutropenia	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.	Day 0 up to Day 14	No
Secondary	Absolute Neutrophil Count (ANC)	The mean values for ANC based on blood tests performed on Day 0 (before starting the study treatment) constitute a Baseline measure for ANC.	Baseline (Day 0)	No
Secondary	Percentage of Participants With Defervescence by Plasma Level of Itraconazole	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.	Day 5	No
Secondary	Plasma Concentration of Itraconazole by Overall Success Rate (OSR) in Participants Who Received the Study Treatment	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.	Day 5	No
Secondary	Percentage of Participants With Baseline Fungal Infection	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.	Baseline (Day 0)	No
Secondary	Plasma Concentration of Itraconazole by Breakthrough Fungal Infection	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.	Day 5	No