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

Invasive Aspergillosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00163722
• Other study ID #: 55/05
• Secondary ID: ALLG SC01NHMRC P
• Status: Completed
• Phase: Phase 3
• First received: September 11, 2005
• Last updated: February 17, 2013
• Start date: September 2005
• Est. completion date: August 2011

Study information

• Verified date: September 2005
• Source: Bayside Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: August 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Aspergillosis
• Invasive Aspergillosis

Intervention

Other:
• Culture and histology

• Aspergillus galactomannan and PCR

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	St. Vincent's Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Sydney	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
Bayside Health	National Health and Medical Research Council, Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sub-group analysis according to type of antifungal prophylaxis, underlying disease and centre		26 weeks of follow-up	No
Primary	The proportion of patients treated with at least 1 course of empiric antifungal therapy as per protocol definition at 26 weeks following randomisation		26 weeks of follow-up	No
Secondary	Invasive Aspergillosis related mortality rates		26 weeks of follow-up	No
Secondary	Other invasive fungal infection-related (IFI) mortality rates		26 weeks of follow-up	No
Secondary	All-cause mortality rates		26 weeks of follow-up	No
Secondary	Nephrotoxicity rates		26 weeks of follow-up	Yes
Secondary	Hepatotoxicity rates		26 weeks of follow-up	Yes
Secondary	Total number of courses of empiric antifungal therapy		26 weeks of follow-up	No
Secondary	Cost data associated with treatment and complications.	To include number of hospital admissions, hospital length of stay, total duration of antifungal therapy and number of invasive procedures to diagnose invasive aspergillosis	26 weeks of follow-up	No
Secondary	Incidence of proven, probable and possible invasive aspergillosis		26 weeks of follow-up	No
Secondary	Incidence of proven, probable and possible other invasive fungal disease besides invasive aspergillosis		26 weeks of follow-up	No