A Multicentre Randomised Controlled Trial Comparing Two Strategies for the Diagnosis of Invasive Aspergillosis in High-risk Haematology Patients

This study has been completed.
Sponsor:
Collaborator:
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
Bayside Health
ClinicalTrials.gov Identifier:
NCT00163722
First received: September 11, 2005
Last updated: February 17, 2013
Last verified: September 2005

September 11, 2005
February 17, 2013
September 2005
January 2011   (final data collection date for primary outcome measure)
The proportion of patients treated with at least 1 course of empiric antifungal therapy as per protocol definition at 26 weeks following randomisation [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: No ]
The proportion of patients treated with at least 1 course of empiric antifungal therapy as per protocol definition at 26 weeks following randomisation
Complete list of historical versions of study NCT00163722 on ClinicalTrials.gov Archive Site
  • Invasive Aspergillosis related mortality rates [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: No ]
  • Other invasive fungal infection-related (IFI) mortality rates [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: No ]
  • All-cause mortality rates [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: No ]
  • Nephrotoxicity rates [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: Yes ]
  • Hepatotoxicity rates [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: Yes ]
  • Total number of courses of empiric antifungal therapy [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: No ]
  • Cost data associated with treatment and complications. [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: No ]
    To include number of hospital admissions, hospital length of stay, total duration of antifungal therapy and number of invasive procedures to diagnose invasive aspergillosis
  • Incidence of proven, probable and possible invasive aspergillosis [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: No ]
  • Incidence of proven, probable and possible other invasive fungal disease besides invasive aspergillosis [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: No ]
  • Invasive Aspergillosis related mortality rates
  • Other invasive fungal infection-related (IFI) mortality rates
  • All-cause mortality rates
  • Mean number of hospital admissions
  • Median hospital length of stay
  • Total duration of antifungal therapy
  • Nephrotoxicity rates
  • Hepatotoxicity rates
  • Median number of courses of empiric antifungal therapy
  • Median number of invasive procedures performed to diagnose IA
  • Cost data associated with treatment and complications.
  • All secondary outcomes will be measured at 26 weeks post randomisation
Sub-group analysis according to type of antifungal prophylaxis, underlying disease and centre [ Time Frame: 26 weeks of follow-up ] [ Designated as safety issue: No ]
Not Provided
 
A Multicentre Randomised Controlled Trial Comparing Two Strategies for the Diagnosis of Invasive Aspergillosis in High-risk Haematology Patients
A Multicentre Randomised Controlled Trial Comparing the Current Standard Diagnostic Strategy for Invasive Aspergillosis to the New Diagnostic Strategy for Invasive Aspergillosis in High-Risk Haematology Patients in Order to Determine Which Strategy Results in the Lower Rates of Use of Empiric Antifungal Therapy

Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of infection with Aspergillus (which is called Invasive Aspergillosis)are those with acute leukaemia who are having chemotherapy and those post bone marrow transplantation. Currently 15% of those at high-risk develop Invasive Aspergillosis and 60-90% of those with Invasive Aspergillosis die.

The main reason for this high death rate is that our current diagnostic tests are not good at detecting infection or often only detect the infection at advanced stages when treatment is ineffective. Because of the limitations of current diagnostic tests the current practice is to give empiric antifungal therapy (EAFT) early to treat suspected Invasive Aspergillosis. However studies have demonstrated that this therapy has only resulted in a minor reduction in the mortality rates and it also causes significant drug toxicity. It is a suboptimal treatment modality.

New tests have recently been developed to diagnose Invasive Aspergillosis. These tests are for the detection of an Aspergillus protein in blood and for the detection of Aspergillus DNA in blood. Available data suggests that these new tests make an early diagnosis and seem to be able to monitor responses to treatment. However no study has been reported to date which demonstrates that the use of these tests can impact on important patient outcomes. This trial is being performed to determine whether the use of the new diagnostic tests to guide antifungal therapy will help improve treatment of Invasive Aspergillosis, reduce drug toxicity and reduce the death rate in the high-risk patients as compared with the current standard method of diagnosis and treatment with EAFT.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Invasive Aspergillosis
  • Other: Culture and histology
  • Other: Aspergillus galactomannan and PCR
  • Active Comparator: Standard diagnostic strategy of culture and histology
    The standard-diagnostic strategy was designed to be consistent with the 2002 guidelines for antimicrobial use in neutropenic patients with cancer. When an invasive fungal infection was suspected (e.g. persistent fevers) cultures of blood, urine, sputum (if available) and faeces (if clinically indicated), and HRCT scans of chest were performed. Bronchoscopy and biopsies were performed according to institutional protocols. Empiric antifungal therapy was recommended whilst undergoing these investigations and was continued, de-escalated to prophylaxis, or changed to treatment of invasive aspergillosis or other IFD according to test results.
    Intervention: Other: Culture and histology
  • Experimental: Aspergillus galactomannan and PCR directed
    Results of once to twice weekly testing with Aspergillus galactomannan and PCR directed the timing of CT scan performance and whether antifungal therapy was given
    Intervention: Other: Aspergillus galactomannan and PCR
Morrissey CO, Chen SC, Sorrell TC, Bradstock KF, Szer J, Halliday CL, Gilroy NM, Schwarer AP, Slavin MA. Design issues in a randomized controlled trial of a pre-emptive versus empiric antifungal strategy for invasive aspergillosis in patients with high-risk hematologic malignancies. Leuk Lymphoma. 2011 Feb;52(2):179-93. doi: 10.3109/10428194.2010.542600. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
240
August 2011
January 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

Patients fulfilling all the following criteria will be eligible for enrolment 1. Aged 18-80 years 2. Undergoing allogeneic haematopoietic stem cell transplantation (HSCT) for any reason OR Undergoing intensive combination chemotherapy for acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL) 3. Has given written informed consent.

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Exclusion Criteria:

Patients with any of the following will be ineligible for enrolment 1. Other immunocompromised states (e.g. HIV infection, solid organ transplantation, autoimmune conditions treated with immunosuppressants etc.) besides those outlined in the inclusion criteria above 2. Currently enrolled in an antifungal treatment trial (not an antifungal prophylaxis trial) 3. Past history of proven or probable IA (as per standardized definitions) during a previous cycle of chemotherapy 4. Currently have active IA or other active invasive fungal infection 5. Prior enrolment in this study

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Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Australia
 
NCT00163722
55/05, ALLG SC01, NHMRC Project Grant 331305
Yes
Bayside Health
Bayside Health
National Health and Medical Research Council, Australia
Principal Investigator: Monica Slavin, MB BS FRACP Infectious Diseases Unit, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Victoria, Australia
Principal Investigator: Orla Morrissey, MB BCh FRACP Infectious Diseases Unit, Alfred Hospital, Level 2, Burnet Institute, Commercial Road, Melbourne, Victoria, 3004, Australia
Bayside Health
September 2005

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP