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

NCT00163722 | Completed Phase 3 DMC

• 3 other identifiers: 55/05ALLG SC01NHMRC Project Grant 331305
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 6

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.

Conditions

Invasive Aspergillosis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (9)

• Invasive Aspergillosis related mortality rates

  26 weeks of follow-up

• Other invasive fungal infection-related (IFI) mortality rates

  26 weeks of follow-up

• All-cause mortality rates

  26 weeks of follow-up

• Nephrotoxicity rates

  26 weeks of follow-up

• Hepatotoxicity rates

  26 weeks of follow-up

Other Outcomes (1)

• Sub-group analysis according to type of antifungal prophylaxis, underlying disease and centre

  26 weeks of follow-up

Study Arms (2)

Standard diagnostic strategy of culture and histology

ACTIVE COMPARATOR

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.

Other: Culture and histology

Aspergillus galactomannan and PCR directed

EXPERIMENTAL

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

Other: Aspergillus galactomannan and PCR

Interventions

Culture and histology OTHER

Standard diagnostic strategy of culture and histology

Aspergillus galactomannan and PCR OTHER

Aspergillus galactomannan and PCR directed

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Bayside Health: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (6)

St. Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3052, Australia

Location

Related Publications (2)

• 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.

  PMID: 23639612 DERIVED

• 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.

  PMID: 21281234 DERIVED

MeSH Terms

Interventions

Culture Techniques; Polymerase Chain Reaction

Intervention Hierarchy (Ancestors)

In Vitro Techniques; Investigative Techniques; Nucleic Acid Amplification Techniques; Genetic Techniques

Study Officials

• Monica Slavin, MB BS FRACP

  Infectious Diseases Unit, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Victoria, Australia

  PRINCIPAL INVESTIGATOR

• Orla Morrissey, MB BCh FRACP

  Infectious Diseases Unit, Alfred Hospital, Level 2, Burnet Institute, Commercial Road, Melbourne, Victoria, 3004, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2005
• First Posted: September 14, 2005
• Study Start: September 1, 2005
• Primary Completion: January 1, 2011
• Study Completion: August 1, 2011
• Last Updated: February 20, 2013

Record last verified: 2005-09

Locations

AU (6)