Back to resultsA Study Comparing the Efficacy of Intravenous Followed by Oral Itraconazole With Intravenous Caspofungin For Empiric Antifungal Therapy in Neutropenic Participants With Hematological Malignancy
Primary Purpose
Hematologic Neoplasms
Status
Terminated
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Itraconazole
Caspofungin
Sponsored by
About this trial
This is an interventional treatment trial for Hematologic Neoplasms
Eligibility Criteria
Inclusion Criteria:
- Participant must be hospitalized with hematologic malignancy treated by myelosuppressive therapy and/or Hematopoietic stem cell transplantation
- Participant must have a diagnosis of neutropenia with neutrophil count < 500/microliters (mcL) (0.5 × 10^9/ liters [L]) for at least 96 hours at screening
- Participant must have a diagnosis of fever and meet the following criteria: 1) Oral/rectal temperature greater than or equal to (>=) 38 degree celsius or axillary temperature (>=) 37.5 degree celsius and is not considered related to blood products transfusion or drug fever, 2) Not responding to broad-spectrum gram-positive and gram-negative antibiotics for 4-7 days with or without signs and symptoms that potentially attributable to deep fungal infection and 3) Defervescence within 3 days after the first broad-spectrum antibiotics but recurrence afterwards.
- A woman of childbearing potential must have a negative serum (beta human chorionic gonadotropin [b hCG]) and pregnancy test at screening
- A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study period and until the menstrual period following the end of study treatment
Exclusion Criteria:
- Is concomitantly using other systematic antifungal drugs as empirical treatment
- Has evidence of inadequately managed bacterial infection
- Is currently receiving any Cytochrome P450 3A4 (CYP3A4)-metabolized/P-glycoprotein-transported drugs (including but not limited to cisapride, pimozide, quinidine, dofetilide, levacetylmethadol, terfenadine, astemizole, mizolastine, bepridil, sertindole, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase) inhibitor [for example, simvastatin, lovastatin], oral midazolam, triazolam, ergot alkaloids [eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine] and nisoldipine) that should be prohibited in this study
- Has known allergy, intolerance or hypersensitivity to azole and echinocandin antifungals or its excipients
- Has a contraindication to the use of sodium chloride injection
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Itraconazole
Caspofungin
Arm Description
Outcomes
Primary Outcome Measures
Response Rate Measured by the Percentage of Participants That Achieve all of the Following 5 Composite Endpoints
Response rate in each of the 2 treatment groups will be measured by the percentage of participants that achieve all of the following 5 composite endpoints: 1) survival for 7 days after completion of treatment, 2) absence of breakthrough invasive fungal infection during the study drug administration and within the first 7 days after completion of treatment, 3) successful treatment of baseline fungal infection, 4) defervescence and 5) no premature withdrawal from the study due to drug-related toxicity or lack of efficacy.
Secondary Outcome Measures
Percentage of Participants With Survival for 7 Days After Completion of Treatment
Percentage of Participants With Absence of Breakthrough Invasive Fungal Infection
Absence of breakthrough invasive fungal infection is defined as the clinically or/and microbiologically documented fungal infection with an onset on or after day 3 of the study treatment during the study drug administration and within the first 7 days after completion of treatment.
Percentage of Participants With Successful Treatment of Baseline Fungal Infection
Successful treatment of baseline fungal infection is defined as the clinically and microbiologically documented fungal infection with an onset within screening to 2 days after the study treatment.
Percentage of Participants With Defervescence During the Period of Neutropenia
Defervescence is defined as oral/rectal temperature less than (<) 38 degree celsius or axillary temperature (<) 37.5 degree celsius for over 48 hours) during the period of neutropenia.
Percentage of Participants With No Premature Withdrawal From the Study due to Drug-related Toxicity or Lack of Efficacy
Response Rate Measured by the Percentage of Participants That Achieve all of the Following 5 Composite Endpoints With Oral Administration of Itraconazole
Response rate will be measured by the percentage of participants (who received oral administration of itraconazole) that achieve all of the following 5 composite endpoints: 1) survival for 7 days after completion of treatment, 2) absence of breakthrough invasive fungal infection during the study drug administration and within the first 7 days after completion of treatment, 3) successful treatment of baseline fungal infection, 4) defervescence and 5) no premature withdrawal from the study due to drug-related toxicity or lack of efficacy.
Full Information
NCT ID
NCT02895529
First Posted
September 6, 2016
Last Updated
May 2, 2019
Sponsor
Xian-Janssen Pharmaceutical Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02895529
Brief Title
A Study Comparing the Efficacy of Intravenous Followed by Oral Itraconazole With Intravenous Caspofungin For Empiric Antifungal Therapy in Neutropenic Participants With Hematological Malignancy
Official Title
A Multicenter, Randomized Trial Comparing The Efficacy of Intravenous Followed by Oral Itraconazole With Intravenous Caspofungin For Empiric Antifungal Therapy in Neutropenic Subjects With Hematological Malignancy
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
Study is a commitment for license renew, we target on Apr19 submission, considering timeline, a cut off should be scheduled in Apr18.
Study Start Date
November 30, 2016 (Actual)
Primary Completion Date
May 2, 2018 (Actual)
Study Completion Date
May 2, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xian-Janssen Pharmaceutical Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to investigate the hypothesis that the efficacy of intravenous (IV) itraconazole followed by oral itraconazole is non-inferior to that of intravenous caspofungin as empiric therapy for suspected fungal infection participants with fever and neutropenia.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Itraconazole
Arm Type
Experimental
Arm Title
Caspofungin
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Itraconazole
Intervention Description
Participants will receive 200 milligram (mg) of itraconazole intravenously (IV) twice daily on Day 1 and Day 2, followed by 200 mg once daily through Day 14. From Day 15 to Day 28, participants will receive 200 mg (20 milliliters [mL]) of itraconazole oral solution orally twice daily. Participants, who are not suitable for oral administration of itraconazole based on the investigator's judgment, will receive 200 mg of itaconazole IV once daily from Day 15 to Day 28.
Intervention Type
Drug
Intervention Name(s)
Caspofungin
Intervention Description
Participants will receive 70 mg of caspofungin IV once daily on Day 1 followed by 50 mg IV infusion once daily thereafter through Day 28.
Primary Outcome Measure Information:
Title
Response Rate Measured by the Percentage of Participants That Achieve all of the Following 5 Composite Endpoints
Description
Response rate in each of the 2 treatment groups will be measured by the percentage of participants that achieve all of the following 5 composite endpoints: 1) survival for 7 days after completion of treatment, 2) absence of breakthrough invasive fungal infection during the study drug administration and within the first 7 days after completion of treatment, 3) successful treatment of baseline fungal infection, 4) defervescence and 5) no premature withdrawal from the study due to drug-related toxicity or lack of efficacy.
Time Frame
Up to 36 days
Secondary Outcome Measure Information:
Title
Percentage of Participants With Survival for 7 Days After Completion of Treatment
Time Frame
Up to 36 days
Title
Percentage of Participants With Absence of Breakthrough Invasive Fungal Infection
Description
Absence of breakthrough invasive fungal infection is defined as the clinically or/and microbiologically documented fungal infection with an onset on or after day 3 of the study treatment during the study drug administration and within the first 7 days after completion of treatment.
Time Frame
Day 3 up to Day 28 (End of treatment [EoT]) and within 7 days after EoT (Day 29 up to Day 35)
Title
Percentage of Participants With Successful Treatment of Baseline Fungal Infection
Description
Successful treatment of baseline fungal infection is defined as the clinically and microbiologically documented fungal infection with an onset within screening to 2 days after the study treatment.
Time Frame
Screening up to Day 3
Title
Percentage of Participants With Defervescence During the Period of Neutropenia
Description
Defervescence is defined as oral/rectal temperature less than (<) 38 degree celsius or axillary temperature (<) 37.5 degree celsius for over 48 hours) during the period of neutropenia.
Time Frame
Up to 36 days
Title
Percentage of Participants With No Premature Withdrawal From the Study due to Drug-related Toxicity or Lack of Efficacy
Time Frame
Up to 36 days
Title
Response Rate Measured by the Percentage of Participants That Achieve all of the Following 5 Composite Endpoints With Oral Administration of Itraconazole
Description
Response rate will be measured by the percentage of participants (who received oral administration of itraconazole) that achieve all of the following 5 composite endpoints: 1) survival for 7 days after completion of treatment, 2) absence of breakthrough invasive fungal infection during the study drug administration and within the first 7 days after completion of treatment, 3) successful treatment of baseline fungal infection, 4) defervescence and 5) no premature withdrawal from the study due to drug-related toxicity or lack of efficacy.
Time Frame
Up to 36 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant must be hospitalized with hematologic malignancy treated by myelosuppressive therapy and/or Hematopoietic stem cell transplantation
Participant must have a diagnosis of neutropenia with neutrophil count < 500/microliters (mcL) (0.5 × 10^9/ liters [L]) for at least 96 hours at screening
Participant must have a diagnosis of fever and meet the following criteria: 1) Oral/rectal temperature greater than or equal to (>=) 38 degree celsius or axillary temperature (>=) 37.5 degree celsius and is not considered related to blood products transfusion or drug fever, 2) Not responding to broad-spectrum gram-positive and gram-negative antibiotics for 4-7 days with or without signs and symptoms that potentially attributable to deep fungal infection and 3) Defervescence within 3 days after the first broad-spectrum antibiotics but recurrence afterwards.
A woman of childbearing potential must have a negative serum (beta human chorionic gonadotropin [b hCG]) and pregnancy test at screening
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study period and until the menstrual period following the end of study treatment
Exclusion Criteria:
Is concomitantly using other systematic antifungal drugs as empirical treatment
Has evidence of inadequately managed bacterial infection
Is currently receiving any Cytochrome P450 3A4 (CYP3A4)-metabolized/P-glycoprotein-transported drugs (including but not limited to cisapride, pimozide, quinidine, dofetilide, levacetylmethadol, terfenadine, astemizole, mizolastine, bepridil, sertindole, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase) inhibitor [for example, simvastatin, lovastatin], oral midazolam, triazolam, ergot alkaloids [eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine] and nisoldipine) that should be prohibited in this study
Has known allergy, intolerance or hypersensitivity to azole and echinocandin antifungals or its excipients
Has a contraindication to the use of sodium chloride injection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xian-Janssen Pharmaceutical Ltd., China Clinical Trial
Organizational Affiliation
Xian-Janssen Pharmaceutical Ltd.
Official's Role
Study Director
Facility Information:
City
Beijign
Country
China
City
Beijing
Country
China
City
Changchun
Country
China
City
Changzhou
Country
China
City
Fuzhou
Country
China
City
Guangzhou
Country
China
City
Guiyang
Country
China
City
Hefei
Country
China
City
Shanghai
Country
China
City
Suzhou
Country
China
City
Tianjin
Country
China
City
Zhengzhou
Country
China
12. IPD Sharing Statement
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR108202&attachmentIdentifier=0de79b23-8b15-44f4-88da-5508c86ad8b0&fileName=CR108202_CSR.pdf&versionIdentifier=
Description
A Multicenter, Randomized Trial Comparing The Efficacy of Intravenous Followed by Oral Itraconazole With Intravenous Caspofungin For Empiric Antifungal Therapy in Neutropenic Subjects With Hematological Malignancy
Learn more about this trial
A Study Comparing the Efficacy of Intravenous Followed by Oral Itraconazole With Intravenous Caspofungin For Empiric Antifungal Therapy in Neutropenic Participants With Hematological Malignancy
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