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Efficacy of Itraconazole as Secondary Prophylaxis in Patients Undergoing Allogeneic Stem Cell Transplantation or Chemotherapy With Prior Invasive Fungal Infection

Primary Purpose

Invasive Fungal Infection

Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Itraconazole
Sponsored by
Zhejiang University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Invasive Fungal Infection focused on measuring hematological malignancy, previous proven or probable invasive fungal infection

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Man or woman between 18 and 65 years of age, inclusive.
  • Patients who affected by hematological malignancies, receiving chemotherapy, or submitted to stem cell transplantation.
  • Patients with previous proven or probable invasive fungal infections, with residual or absent lesions on CT scan or X-ray and the absence of clinical signs of fungal infection at the time of enrollment. Or, possible IFI patients without microbiological evidence but with effective anti-fungal therapy history.

(The diagnosis is according to the definitions of Chinese guideline for the diagnosis and treatment of invasive fungal infections in immunocompromised patients with cancer cancer and hematopoietic stem cell transplant.)

  • Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
  • Lack of clinical symptoms of invasive fungal infection

Exclusion Criteria:

  • Patient has no response to the previous intravenous itraconazole antifungal therapy.
  • Currently taking the contra-indicated medications such as teldane, astemizol, cisapride and HMG-CoA reductase inhibitor（e.g. Simvastatin, ovastatin, oral Midazolam and Triazolam）
  • History of allergy or intolerance to imidazole or azoles anti-fungal agents（e.g. Fluconazol, Itraconazole, Ketoconazole, Miconazole, Clotrimazole）
  • Pregnant women, lactating women or women of child bearing potential without applying valid contraceptive measures
  • Patients with current cardiac dysfunction (especially with congestive heart failure) or with the history of congestive heart failure
  • Patients with severe liver dysfunction (aminotransferase levels ≥5 times the upper limit of normal and total bilirubin level ≥3mg/dL(51.3 μmol/L); or the severity of liver dysfunction does not match this criteria but the patient is in bad condition and not suitable for this trial( doctors make the decision);
  • Patients with renal insufficiency having serum Ccr level <30ml/min, calculated from the following formula:

Male: Ccr (ml/min)=(140-age)×weight (kg) /(0.8136×Crea (μmol/L) ) Female:Ccr (ml/min)=(140-age)×weight (kg) ×0.85/(0.8136× Crea (μmol/L) )

  • Patients received any experimental drug within 10 days before the planned start of treatment.
  • Patients with bad whole body status and not suitable for the trial (doctors make the decision)

Sites / Locations

  • The First Hospital of Zhejiang Medical Colleage Zhejiang University

Outcomes

Primary Outcome Measures

successful prophylaxis rate
The rate of patients without documented relapse of the fungal infection and the absence of new proven, probable or possible IFI at the end of secondary prophylaxis treatment and 7 days later.

Secondary Outcome Measures

rate of patients who developed persistent fever or pulmonary infiltrates of unknown etiology
The rate of patients who developed persistent fever or pulmonary infiltrates of unknown etiology. For those neutropenic patients with persistent fever, antibiotics should be used according to the International anti-infection guideline in order to exclude the possibility of bacterial infection. If the fever persists after 5-6 days' combination use of itraconazole and antibiotics, this case would be regarded as "secondary prophylaxis failure" and the trial is terminated , while doctors should search for further clinical therapy to save the patient.

Full Information

First Posted
September 9, 2010
Last Updated
October 13, 2011
Sponsor
Zhejiang University
Collaborators
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Zhejiang Provincial Hospital of TCM, First Affiliated Hospital of Wenzhou Medical University, Guangdong Provincial People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01198236
Brief Title
Efficacy of Itraconazole as Secondary Prophylaxis in Patients Undergoing Allogeneic Stem Cell Transplantation or Chemotherapy With Prior Invasive Fungal Infection
Official Title
Efficacy of Itraconazole as Secondary Prophylaxis in Patients Undergoing Allogeneic Stem Cell Transplantation or Chemotherapy With Prior Invasive Fungal Infection
Study Type
Interventional

2. Study Status

Record Verification Date
October 2011
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Zhejiang University
Collaborators
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Zhejiang Provincial Hospital of TCM, First Affiliated Hospital of Wenzhou Medical University, Guangdong Provincial People's Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Invasive fungal infections (IFI) remain the major cause of death among neutropenic patients receiving chemotherapy for leukemia, or submitted to stem cell transplantation. Patients with a history of invasive fungal infection (IFI) are at high risk of developing relapse and fatal complications. Prompt intensive antifungal therapy, have improved responses and survival, allowing an increase of antifungal treatments, including secondary antifungal prophylaxis. Few studies have addressed the role of previous IFI in the feasibility of stem cell transplant, or the secondary prophylaxis with antifungal drugs in preventing recurrence of infection after transplantation. However, given the lack of prospective studies, the role of secondary antifungal prophylaxis remains unclear. Itraconazole is a wide-spectrum triazole antifungal agent active against Candida albicans, non-albicans, Aspergillus spp., Blastomyces dermatitidis, Blastomyces coccidioides, Cryptococcus neoformans, Sporothrix schenkii, Paracoccidioides brasiliensis, Histoplasma spp. and various kinds of yeast fungi and mycetes. The role of itraconazole IFI prophylaxis treatment has been proved by many interventional studies. In this prospective, multicentric study of secondary prophylaxis, itraconazole will be given at standard dose to patients undergoing allogeneic stem cell transplantation or chemotherapy with prior invasive fungal infection, to assess the efficacy and safety of itraconazole secondary prophylaxis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Fungal Infection
Keywords
hematological malignancy, previous proven or probable invasive fungal infection

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Itraconazole
Other Intervention Name(s)
Sporanox IV and Oral solution
Intervention Description
Itraconazole will be administered intravenously 2×200 mg/d(200mg twice a day, with 12 hours interval, and should be completed in no less than 60 minutes each time) in the first two days of treatment as a loading dose, then 200mg/d intravenously (200mg once a day with 24 hours interval and completed in no less than 60 minutes) until the end of the at-risk period. In transplant patients, the end of "at-risk period" is defined as a stable engraftment of 1*109/L neutrophil cells; in patients who have undergone chemotherapy, it is defined as the resolution of neutropenia (neutrophil cells> 0.5*109/L). If needed, the patients will take itraconazole solution orally after intravenous administration.
Primary Outcome Measure Information:
Title
successful prophylaxis rate
Description
The rate of patients without documented relapse of the fungal infection and the absence of new proven, probable or possible IFI at the end of secondary prophylaxis treatment and 7 days later.
Time Frame
more than 7 days
Secondary Outcome Measure Information:
Title
rate of patients who developed persistent fever or pulmonary infiltrates of unknown etiology
Description
The rate of patients who developed persistent fever or pulmonary infiltrates of unknown etiology. For those neutropenic patients with persistent fever, antibiotics should be used according to the International anti-infection guideline in order to exclude the possibility of bacterial infection. If the fever persists after 5-6 days' combination use of itraconazole and antibiotics, this case would be regarded as "secondary prophylaxis failure" and the trial is terminated , while doctors should search for further clinical therapy to save the patient.
Time Frame
at least 7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Man or woman between 18 and 65 years of age, inclusive. Patients who affected by hematological malignancies, receiving chemotherapy, or submitted to stem cell transplantation. Patients with previous proven or probable invasive fungal infections, with residual or absent lesions on CT scan or X-ray and the absence of clinical signs of fungal infection at the time of enrollment. Or, possible IFI patients without microbiological evidence but with effective anti-fungal therapy history. (The diagnosis is according to the definitions of Chinese guideline for the diagnosis and treatment of invasive fungal infections in immunocompromised patients with cancer cancer and hematopoietic stem cell transplant.) Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Lack of clinical symptoms of invasive fungal infection Exclusion Criteria: Patient has no response to the previous intravenous itraconazole antifungal therapy. Currently taking the contra-indicated medications such as teldane, astemizol, cisapride and HMG-CoA reductase inhibitor（e.g. Simvastatin, ovastatin, oral Midazolam and Triazolam） History of allergy or intolerance to imidazole or azoles anti-fungal agents（e.g. Fluconazol, Itraconazole, Ketoconazole, Miconazole, Clotrimazole） Pregnant women, lactating women or women of child bearing potential without applying valid contraceptive measures Patients with current cardiac dysfunction (especially with congestive heart failure) or with the history of congestive heart failure Patients with severe liver dysfunction (aminotransferase levels ≥5 times the upper limit of normal and total bilirubin level ≥3mg/dL(51.3 μmol/L); or the severity of liver dysfunction does not match this criteria but the patient is in bad condition and not suitable for this trial( doctors make the decision); Patients with renal insufficiency having serum Ccr level <30ml/min, calculated from the following formula: Male: Ccr (ml/min)=(140-age)×weight (kg) /(0.8136×Crea (μmol/L) ) Female:Ccr (ml/min)=(140-age)×weight (kg) ×0.85/(0.8136× Crea (μmol/L) ) Patients received any experimental drug within 10 days before the planned start of treatment. Patients with bad whole body status and not suitable for the trial (doctors make the decision)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
He Huang, MD
Organizational Affiliation
The First Hopspital of Zhejiang Medical Colleage, Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Hospital of Zhejiang Medical Colleage Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
15034546
Citation
Cordonnier C, Maury S, Pautas C, Bastie JN, Chehata S, Castaigne S, Kuentz M, Bretagne S, Ribaud P. Secondary antifungal prophylaxis with voriconazole to adhere to scheduled treatment in leukemic patients and stem cell transplant recipients. Bone Marrow Transplant. 2004 May;33(9):943-8. doi: 10.1038/sj.bmt.1704469.
Results Reference
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PubMed Identifier
17529996
Citation
de Fabritiis P, Spagnoli A, Di Bartolomeo P, Locasciulli A, Cudillo L, Milone G, Busca A, Picardi A, Scime R, Bonini A, Cupelli L, Chiusolo P, Olivieri A, Santarone S, Poidomani M, Fallani S, Novelli A, Majolino I. Efficacy of caspofungin as secondary prophylaxis in patients undergoing allogeneic stem cell transplantation with prior pulmonary and/or systemic fungal infection. Bone Marrow Transplant. 2007 Aug;40(3):245-9. doi: 10.1038/sj.bmt.1705720. Epub 2007 May 28.
Results Reference
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Efficacy of Itraconazole as Secondary Prophylaxis in Patients Undergoing Allogeneic Stem Cell Transplantation or Chemotherapy With Prior Invasive Fungal Infection

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