Condition category
Cancer
Date applied
19/05/2010
Date assigned
19/05/2010
Last edited
16/05/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Mrs Denise Andrews

ORCID ID

Contact details

Ground Floor
Pathology Block
St. Bartholomews Hospital
West Smithfield
London
EC1A 7BE
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2242

Study information

Scientific title

Early diagnosis of invasive aspergillosis in a high risk group of patients using serum and bronchoalveolar lavage fluid, real time polymerase chain reaction (PCR) and galactomannan enzyme-linked immunosorbent assay (ELISA)

Acronym

Study hypothesis

Invasive fungal infections in immunocompromised patients carry a high mortality and diagnosis can be very dificult. Treatment is often commenced empirially in the context of a febrile illness and neutropenia unresponsive to antibiotics. Antifungal agents are expensive and toxic for this hospital-acquired infection. Improvement in diagnostic techniques would allow genuine fungal infection to be treated early and unnesssary harmful therapy to be withheld.

The aim of the study is to determine characteristics for two diagnostics tests in invasive aspergillosis (IA) in patients at high risk with neutropenia following intensive chemotherapy or allogenic bone marrow transpant. This will include sensitivity and specificity and the calculation of positive and negative predictive values for our population. This is a single centre prospective study, which requires twice weekly blood samples from inpatients fulfilling the inclusion criteria in addition to collection of exhaled breath condensate, which will be measured from the onset of neutropenia at weekly intervals until resolution of fever or recovery of the neutrophil count.

This is a novel application for a well recognised, well tolerated, non-invasive technique. As such, data from EBC will be analysed after the first 10 patients to assess its utility. In patients with abnormal chest radiology, bronchoscopy and bronchoalveolar lavage (BAC) 72 hours after onset of fever unresponsive to routine antibiotics will be carried out as part of routine management. A part of the sample obtained will also be used in this study, where applicable. Simple clinical information will be collected during their admission. Recovery of the neutrophil count or from infection will signify the end of the study period. Each course of chemotherapy will count as a separate episode therefore patients may be included in the trial more than once. Consent will be sought separately for each inclusion.

As of 17/02/2011 the anticipated end date for this trial has been updated from 01/09/2008 to 31/07/2011.

Ethics approval

East London and the City Research Ethics Board on 01/06/2005 (ref: 05/Q0603/68)

Study design

Single centre non-randomised observational diagnosis and validation of investigative/therapeutic process study

Primary study design

Observational

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Lung Cancer; Disease: Miscellaneous

Intervention

Study interventions will begin prior to the start of chemo/immunosuppression and continue until recovery of the neutrophil count to greater than 1.0 x 10^9/L. If fungal infection occurs, then testing should continue until discharge. Samples will be analysed in batches. A febrile episode is defined as any of the following:
1. Temperature greater than 38°C for more than 4 hours
2. Temperature greater than 38°C on two occassions greater than 4 hours apart within a 24 hour period
3. Temp greater than 38.5°C on one occassion

PCR: PCR for fungal DNA will be performed twice weekly.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

GM ELISA from serum and BALF, measured within 6 months of the conclusion of the study

Secondary outcome measures

Measured within 6 months of the conclusion of the study:
1. To establish cut off points to rule IA in or out
2. GM Elisa in prognosis
3. Inflamatory marker and cytokine profil in EBC
4. Non-invasive EBC in IA
5. PCR for Aspergillus
6. PCR for Aspergillus from blood and BALF
7. Repeated measures over time or a combination of markers
8. Role of BAL

Overall trial start date

01/06/2005

Overall trial end date

31/07/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Informed consent
2. Patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and acute lymphoblastic leukemia (ALL) undergoing intensive chemotherapy (predicted neutropenia of less than 0.5 x 10^9/L for greater than 10 days) and/or receiving high dose steroids
3. Patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT)
4. Patients requiring high dose steroids for graft versus host disease post HSCT
5. Patients with a history of probable or proven invasive aspergillosis and having chemotherapy, regardless of their underlying haematological malignancy
6. Aged greater than 18 years, either sex

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned sample size: 300

Participant exclusion criteria

1. Inability to give informed consent
2. Patients aged less than 18 years
3. Pre-existing chest disease

Recruitment start date

01/06/2005

Recruitment end date

31/07/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Ground Floor, Pathology Block
London
EC1A 7BE
United Kingdom

Sponsor information

Organisation

Barts and The London NHS Trust (UK)

Sponsor details

Queen Mary's Innovation Centre
5 Walden Street
London
E1 2EF
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.bartsandthelondon.nhs.uk/

Funders

Funder type

Industry

Funder name

Gilead Sciences Inc (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Pfizer (UK)

Alternative name(s)

Pfizer Inc.

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes