Clinical trial NCT00163722: A Multicentre Randomised Controlled Trial Comparing Two Strategies for the Diagnosis of Invasive Aspergillosis in High-risk Haematology Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Invasive Aspergillosis
Lead sponsor: Bayside Health
Sponsor class: OTHER_GOV
Collaborators: name: National Health and Medical Research Council, Australia
First posted: 2005-09-14
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility 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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Primary outcomes:
measure: The proportion of patients treated with at least 1 course of empiric antifungal therapy as per protocol definition at 26 weeks following randomisation
timeFrame: 26 weeks of follow-up
Secondary outcomes:
measure: Invasive Aspergillosis related mortality rates
timeFrame: 26 weeks of follow-up
measure: Other invasive fungal infection-related (IFI) mortality rates
timeFrame: 26 weeks of follow-up
measure: All-cause mortality rates
timeFrame: 26 weeks of follow-up
measure: Nephrotoxicity rates
timeFrame: 26 weeks of follow-up
measure: Hepatotoxicity rates
timeFrame: 26 weeks of follow-up
measure: Total number of courses of empiric antifungal therapy
timeFrame: 26 weeks of follow-up
measure: Cost data associated with treatment and complications.
timeFrame: 26 weeks of follow-up
measure: Incidence of proven, probable and possible invasive aspergillosis
timeFrame: 26 weeks of follow-up
measure: Incidence of proven, probable and possible other invasive fungal disease besides invasive aspergillosis
timeFrame: 26 weeks of follow-up
Other outcomes:
measure: Sub-group analysis according to type of antifungal prophylaxis, underlying disease and centre
timeFrame: 26 weeks of follow-up
Locations:
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: Infectious Diseases Unit, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Victoria, Australia
name: Monica Slavin, MB BS FRACP
role: PRINCIPAL_INVESTIGATOR
affiliation: Infectious Diseases Unit, Alfred Hospital, Level 2, Burnet Institute, Commercial Road, Melbourne, Victoria, 3004, Australia
name: Orla Morrissey, MB BCh FRACP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morrissey CO, Chen SC, Sorrell TC, Milliken S, Bardy PG, Bradstock KF, Szer J, Halliday CL, Gilroy NM, Moore J, Schwarer AP, Guy S, Bajel A, Tramontana AR, Spelman T, Slavin MA; Australasian Leukaemia Lymphoma Group and the Australia and New Zealand Mycology Interest Group. Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: a randomised controlled trial. Lancet Infect Dis. 2013 Jun;13(6):519-28. doi: 10.1016/S1473-3099(13)70076-8. Epub 2013 Apr 30.
citation: 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.