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

Condition(s) targeted: Invasive Aspergillosis

Intervention: Aspergillus galactomannan ELISA and Aspergillus PCR assay (Device)

Phase: Phase 3

Status: Recruiting

Sponsored by: Bayside Health

Official(s) and/or principal investigator(s):
Monica Slavin, MB BS FRACP, Principal Investigator, Affiliation: Infectious Diseases Unit, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Victoria, Australia
Orla Morrissey, MB BCh FRACP, Principal Investigator, Affiliation: Infectious Diseases Unit, Alfred Hospital, Level 2, Burnet Institute, Commercial Road, Melbourne, Victoria, 3004, Australia

Overall contact:
Orla Morrissey, MB BCh FRACP, Phone: 61 3 9276 2000, Ext: 2631, Email: o.morrissey@alfred.org.au

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.

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 design: Diagnostic, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: The proportion of patients treated with at least 1 course of empiric antifungal therapy as per protocol definition at 26 weeks following randomisation

Secondary outcome:

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

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

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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Orla Morrissey, MB BCh FRACP, Phone: 61 3 9276 2000, Ext: 2631, Email: o.morrissey@alfred.org.au

Westmead Hospital, Sydney, New South Wales 2145, Australia; Recruiting
Tania Sorrell, MD BS FRACP, Phone: 61 2 9845 7191, Ext: 7191, Email: tanias@icpmr.wsahs.nsw.gov.au
Sharon Chen, MB BS FRACP, Phone: 61 2 9845 6255, Ext: 6255, Email: sharonc@icpmr.wsahs.nsw.gov.au
Tania Sorrell, MD BS FRACP, Principal Investigator

St. Vincent's Hospital, Sydney, New South Wales 2010, Australia; Not yet recruiting
Sam Milliken, MB BS FRACP, Phone: 61 2 8382 2697, Email: smilliken@stvincents.com.au
Rachelle Carter, RN, Phone: 61 2 8382 2697, Email: rcarter@stvincents.com.au
Sam Milliken, MB BS FRACP, Principal Investigator

Alfred Hospital, Melbourne, Victoria 3004, Australia; Recruiting
Orla Morrissey, MB BCh FRAP, Phone: 61 3 9276 2000, Ext: 2631, Email: o.morrissey@alfred.org.au
Tim Luff, RN, Phone: 61 3 9207 1884, Ext: 1884, Email: t.luff@alfred.org.au
Orla Morrissey, MB BCh FRACP, Principal Investigator

Royal Melbourne Hospital, Melbourne, Victoria 3052, Australia; Recruiting
Monica Slavin, MB BS FRACP, Phone: 61 3 9342 7000, Ext: 7212, Email: Monica.Slavin@mh.org.au
Tim Luff, RN, Phone: 61 3 9342 7000, Ext: 8896, Email: Tim.Luff@mh.org.au
Monica Slavin, MB BS FRACP, Principal Investigator

Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia; Not yet recruiting
Monica Slavin, MB BS FRACP, Phone: 61 3 9656 1111, Ext: 1526, Email: Monica.Slavin@petermac.org
Miles Prince, MD FRACP, Phone: 61 3 9656 1111, Ext: 1700, Email: Miles.Prince@petermac.org
Monica Slavin, MB BS FRACP, Principal Investigator

Starting date: September 2005
Ending date: March 2009
Last updated: October 2, 2006