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

This study has been completed.
Sponsor:
Collaborators:
Shanghai First People's Hospital
Chinese Medicine Hospital Zhejiang Province
Wenzhou Medical University
Guangdong Provincial People's Hospital
Information provided by:
Zhejiang University
ClinicalTrials.gov Identifier:
NCT01198236
First received: September 9, 2010
Last updated: October 13, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Invasive Fungal Infection
Drug: Itraconazole
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Efficacy of Itraconazole as Secondary Prophylaxis in Patients Undergoing Allogeneic Stem Cell Transplantation or Chemotherapy With Prior Invasive Fungal Infection

Resource links provided by NLM:


Further study details as provided by Zhejiang University:

Primary Outcome Measures:
  • successful prophylaxis rate [ Time Frame: more than 7 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: at least 7 days ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 150
Study Start Date: July 2008
Study Completion Date: November 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Itraconazole

    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.

    Other Name: Sporanox IV and Oral solution
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01198236

Locations
China, Zhejiang
The First Hospital of Zhejiang Medical Colleage Zhejiang University
Hangzhou, Zhejiang, China, 310003
Sponsors and Collaborators
Zhejiang University
Shanghai First People's Hospital
Chinese Medicine Hospital Zhejiang Province
Wenzhou Medical University
Guangdong Provincial People's Hospital
Investigators
Principal Investigator: He Huang, MD The First Hopspital of Zhejiang Medical Colleage, Zhejiang University
  More Information

Publications:
Responsible Party: Shushen Zheng, The president of the Hospital, The First Hospital of Zhejiang Medical Colleage, Zhejiang University
ClinicalTrials.gov Identifier: NCT01198236     History of Changes
Other Study ID Numbers: SpoIV-CHA-IIS-0802, ITRFUN4044
Study First Received: September 9, 2010
Last Updated: October 13, 2011
Health Authority: China: Food and Drug Administration

Keywords provided by Zhejiang University:
hematological malignancy
previous proven or probable invasive fungal infection

Additional relevant MeSH terms:
Mycoses
Itraconazole
Hydroxyitraconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014