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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00163722




Registration number
NCT00163722
Ethics application status
Date submitted
11/09/2005
Date registered
14/09/2005
Date last updated
20/02/2013

Titles & IDs
Public title
A Multicentre Randomised Controlled Trial Comparing Two Strategies for the Diagnosis of Invasive Aspergillosis in High-risk Haematology Patients
Scientific 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
Secondary ID [1] 0 0
ALLG SC01
Secondary ID [2] 0 0
55/05
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Invasive Aspergillosis 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.

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
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The proportion of patients treated with at least 1 course of empiric antifungal therapy as per protocol definition at 26 weeks following randomisation
Timepoint [1] 0 0
26 weeks of follow-up
Secondary outcome [1] 0 0
Invasive Aspergillosis related mortality rates
Timepoint [1] 0 0
26 weeks of follow-up
Secondary outcome [2] 0 0
Other invasive fungal infection-related (IFI) mortality rates
Timepoint [2] 0 0
26 weeks of follow-up
Secondary outcome [3] 0 0
All-cause mortality rates
Timepoint [3] 0 0
26 weeks of follow-up
Secondary outcome [4] 0 0
Nephrotoxicity rates
Timepoint [4] 0 0
26 weeks of follow-up
Secondary outcome [5] 0 0
Hepatotoxicity rates
Timepoint [5] 0 0
26 weeks of follow-up
Secondary outcome [6] 0 0
Total number of courses of empiric antifungal therapy
Timepoint [6] 0 0
26 weeks of follow-up
Secondary outcome [7] 0 0
Cost data associated with treatment and complications.
Timepoint [7] 0 0
26 weeks of follow-up
Secondary outcome [8] 0 0
Incidence of proven, probable and possible invasive aspergillosis
Timepoint [8] 0 0
26 weeks of follow-up
Secondary outcome [9] 0 0
Incidence of proven, probable and possible other invasive fungal disease besides invasive aspergillosis
Timepoint [9] 0 0
26 weeks of follow-up

Eligibility
Key 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.

-
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

-

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2011
Sample size
Target
Accrual to date
Final
240
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Sydney
Recruitment hospital [2] 0 0
Westmead Hospital - Sydney
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [6] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
3002 - Melbourne
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
3052 - Melbourne

Funding & Sponsors
Primary sponsor type
Government body
Name
Bayside Health
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00163722
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Monica Slavin, MB BS FRACP
Address 0 0
Infectious Diseases Unit, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Victoria, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00163722