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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
History of Changes
  Purpose

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.


Condition Intervention Phase
Invasive Aspergillosis
 Other: Culture and histology
Other: Aspergillus galactomannan and PCR
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: 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

Resource links provided by NLM:

MedlinePlus related topics: Aspergillosis Molds
U.S. FDA Resources

Further study details as provided by Bayside Health:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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 ]
Enrollment: 240
Study Start Date: September 2005
Study Completion Date: August 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
 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
 Other: Aspergillus galactomannan and PCR

  Eligibility
Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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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  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: NCT00163722

Locations
Australia, New South Wales
St. Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Westmead Hospital
Sydney, New South Wales, Australia, 2145
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Australia, Victoria
Alfred Hospital
Melbourne, Victoria, Australia, 3004
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia, 3002
Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3052
Sponsors and Collaborators
Bayside Health
National Health and Medical Research Council, Australia
Investigators
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
  More Information

No publications provided by Bayside Health

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Bayside Health
ClinicalTrials.gov Identifier: NCT00163722     History of Changes
Other Study ID Numbers: 55/05, ALLG SC01, NHMRC Project Grant 331305
Study First Received: September 11, 2005
Last Updated: February 17, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Additional relevant MeSH terms:
Aspergillosis
Dermatomycoses
Hyalohyphomycosis
Infection
 Mycoses
Skin Diseases
Skin Diseases, Infectious

ClinicalTrials.gov processed this record on February 27, 2015