Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12605000137695
Ethics application status
Approved
Date submitted
4/08/2005
Date registered
12/08/2005
Date last updated
28/09/2023
Date data sharing statement initially provided
4/08/2023
Date results information initially provided
4/08/2023
Type of registration
Prospectively registered

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 Two Strategies for the Diagnosis of Invasive Aspergillosis in High-Risk Haematology Patients
Secondary ID [1] 113 0
Australasian Leukaemia and Lymphoma Group (ALLG): ALLG SC01
Universal Trial Number (UTN)
Trial acronym
ASPID
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Invasive Aspergillosis 227 0
Condition category
Condition code
Infection 257 257 0 0
Studies of infection and infectious agents
Blood 258 258 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study design: A multicentre, randomised parallel-group trial which compares 2 strategies for the diagnosis of Invasive Aspergillosis (IA) in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) and in patients undergoing intensive combination chemotherapy for acute leukaemia. Eligible patients will be stratified by centre and randomised 1:1 to the either the current standard diagnostic strategy (comparator or control arm) or the new diagnostic strategy (intervention arm) for IA. The study will not be blinded to enrolled patients or participating clinicians. However the assessment of the endpoints/outcomes will be by the Outcome Committee who will be blinded to the patients randomisation status.Experimental Protocol:Comparator arm: The current standard diagnostic work-up for IA will be implemented in patients with persistent or recurrent neutropenic fevers despite broad-spectrum antibiotics. The diagnostic components of this arm include serial blood cultures and serial urine, faeces, sputum and mouth swill samples for fungal culture; chest x-ray, high resolution computerised tomographic (HRCT) scan of thorax; bronchoscopy and culture of bronchoalveolar lavage (BAL) fluid; biopsy for histological examination etc. The results of the tests will determine the type of antifungal therapy given namely, empiric antifungal therapy or fungal therapy for proven or probable IA as per the predefined treatment protocol.New diagnostic strategy (index arm): Screening will be performed with Aspergillus galactomannan enzyme-linked immunosorbent assay (GM-ELISA) and an Aspergillus nested polymerase chain reaction (PCR) assay twice weekly for inpatients and weekly for outpatients. The results of the tests will determine if antifungal therapy is administered as per the same predefined treatment protocol, the timing of HRCT scan and what other procedures (e.g. bronchoscopy and culture of bronchoalveolar lavage (BAL) fluid etc.) are performed to further investigate persistent or recurrent neutropenic fevers. Duration on study:Each patient will be followed using the trial protocol for 26 weeks or until death, if earlier Sample size calculation and duration of study: 300 patients per arm are required to detect a 12% absolute reduction (i.e. from 40% to 28%) in the proportion of patients treated with empiric antifungal therapy. An interim analysis is planned. The expected accrual rate is 240 patients per year, thus the expected duration of the trial including follow-up will be 3 years.
Intervention code [1] 115 0
Diagnosis / Prognosis
Comparator / control treatment
Current standard diagnostic strategy (comparator or control arm)
Control group
Active

Outcomes
Primary outcome [1] 303 0
The proportion of patients treated with at least 1 course of empiric antifungal therapy as per protocol definition
Timepoint [1] 303 0
At 26 weeks following randomisation
Secondary outcome [1] 664 0
IA-related mortality rates
Timepoint [1] 664 0
All secondary outcomes will be measured at 26 weeks post randomisation.
Secondary outcome [2] 665 0
Other invasive fungal infection-related (IFI) mortality rates
Timepoint [2] 665 0
All secondary outcomes will be measured at 26 weeks post randomisation.
Secondary outcome [3] 666 0
all-cause mortality rates
Timepoint [3] 666 0
All secondary outcomes will be measured at 26 weeks post randomisation.
Secondary outcome [4] 667 0
Overall survival rates
Timepoint [4] 667 0
All secondary outcomes will be measured at 26 weeks post randomisation.
Secondary outcome [5] 668 0
Mean number of hospital admissions
Timepoint [5] 668 0
All secondary outcomes will be measured at 26 weeks post randomisation.
Secondary outcome [6] 669 0
Median hospital length of stay
Timepoint [6] 669 0
All secondary outcomes will be measured at 26 weeks post randomisation.
Secondary outcome [7] 670 0
Total duration of antifungal therapy
Timepoint [7] 670 0
All secondary outcomes will be measured at 26 weeks post randomisation.
Secondary outcome [8] 671 0
Nephrotoxicity rates
Timepoint [8] 671 0
All secondary outcomes will be measured at 26 weeks post randomisation.
Secondary outcome [9] 672 0
Hepatotoxicity rates
Timepoint [9] 672 0
All secondary outcomes will be measured at 26 weeks post randomisation.
Secondary outcome [10] 673 0
Median number of courses of empiric antifungal therapy
Timepoint [10] 673 0
All secondary outcomes will be measured at 26 weeks post randomisation.
Secondary outcome [11] 674 0
Median number of invasive procedures performed to diagnose IA and cost data associated with treatment and complications.
Timepoint [11] 674 0
All secondary outcomes will be measured at 26 weeks post randomisation.

Eligibility
Key inclusion criteria
1.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). 2.Has given written informed consent. Non-English speaking patients are eligible once written informed consent is obtained via the appropriate interpreter.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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)
Computer generated allocation in Trial Centre, arm revealed only after patient registration
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer generated
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
31/08/2005
Actual
30/09/2005
Date of last participant enrolment
Anticipated
Actual
12/05/2009
Date of last data collection
Anticipated
Actual
31/12/2009
Sample size
Target
240
Accrual to date
Final
240
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 312 0
Government body
Name [1] 312 0
NHMRC project grant
Country [1] 312 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
-
Country
Australia
Secondary sponsor category [1] 243 0
None
Name [1] 243 0
nil
Address [1] 243 0
Country [1] 243 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1182 0
Royal Melbourne Hospital
Ethics committee address [1] 1182 0
The RMH Parkville
Level 2 South West
300 Grattan St, Parkville, Victoria
Ethics committee country [1] 1182 0
Australia
Date submitted for ethics approval [1] 1182 0
Approval date [1] 1182 0
Ethics approval number [1] 1182 0
Ethics committee name [2] 1183 0
The Alfred Hospital
Ethics committee address [2] 1183 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [2] 1183 0
Australia
Date submitted for ethics approval [2] 1183 0
Approval date [2] 1183 0
31/08/2005
Ethics approval number [2] 1183 0
Ethics committee name [3] 1184 0
MelbournePeter MacCallum Cancer Centre
Ethics committee address [3] 1184 0
Peter MacCallum Cancer Centre
Locked Bag 1, A’Beckett Street
Victoria 8006
Ethics committee country [3] 1184 0
Australia
Date submitted for ethics approval [3] 1184 0
Approval date [3] 1184 0
Ethics approval number [3] 1184 0
Ethics committee name [4] 1185 0
Westmead Hospital
Ethics committee address [4] 1185 0
Darcy Rd, Westmead NSW 2145
Ethics committee country [4] 1185 0
Australia
Date submitted for ethics approval [4] 1185 0
Approval date [4] 1185 0
Ethics approval number [4] 1185 0

Summary
Brief summary
This randomised controlled trial compares the new diagnostic strategy for Invasive Aspergillosis (IA) to the current standard diagnostic strategy. The new diagnostic strategy uses Aspergillus ELISA and an Aspergillus nested PCR assay to diagnose/exclude IA and direct further management including timing of HRCT scan of thorax.

Eligible patients are aged 18-80 and have received an allogeneic haematopoietic stem cell transplant or are undergoing intensive combination chemotherapy for acute myeloid leukaemia or acute lymphoblastic leukaemia.

The study aims to determine which strategy results in lower: rates of empiric antifungal therapy administration; drug–related toxicities; IA-related mortality rates and overall mortality rates.
Trial website
Trial related presentations / publications
O. Morrissey, S. Chen, M. Slavin for the Australia and New Zealand Mycology Interest Group and Australasian Leukaemia Lymphoma Group. Randomized Controlled Trial of Two Diagnostic Strategies for Invasive Aspergillosis (IA) in High-Risk Hematology Patients. 51th ICAAC Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, September 17-20, 2011

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. Leukemia & Lymphoma. 2011;52(2):179-193

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 G, the A, New Zealand Mycology Interest G. 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;13(6):519-528

Macesic, N., Morrissey, C.O. , Liew, D, Gilroy, N, Chen, S.C-A, Slavin, M. Cost-effective analysis of a biomarker-based versus the standard culture and histology-based diagnostic strategy for invasive aspergillosis (IA) in high-risk hematology patients. 19th Congress of the International Society for Human and Animal Mycology (ISHAM), Melbourne, May 2015.
Public notes

Contacts
Principal investigator
Name 35339 0
Address 35339 0
Country 35339 0
Phone 35339 0
Fax 35339 0
Email 35339 0
Contact person for public queries
Name 9304 0
Dr Orla Morrissey
Address 9304 0
Infectious Diseases Unit
Alfred Hospital
Level 2 Burnet Institute
Commercial Road
Melbourne VIC 3004
Country 9304 0
Australia
Phone 9304 0
+61 3 92762000 (Pager 4260)
Fax 9304 0
+61 3 92766557
Email 9304 0
email [email protected]
Contact person for scientific queries
Name 232 0
Dr. Monica Slavin
Address 232 0
Infectious Diseases Unit
Peter MacCallum Cancer Centre
St. Andrew's Place
East Melbourne VIC 3002
Country 232 0
Australia
Phone 232 0
+61 3 96561526
Fax 232 0
Email 232 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified IPD data, for all data collected during the trial
When will data be available (start and end dates)?
Data available 3 months following publication, for an indefinite period
Available to whom?
Data are potentially available to:
• Researchers from not-for-profit organisations
• Commercial organisations
• Other
Based in:
• Any location
Further information:
All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted.
Available for what types of analyses?
Any type of analysis
Assessed on a case-by-case basis
How or where can data be obtained?
Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19924Study protocol  [email protected] Access can be requested via the Health Data Austra... [More Details]



Results publications and other study-related documents

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