Diagnostic and Management Strategies for Invasive Aspergillosis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by King's College Hospital NHS Trust.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
King's College Hospital NHS Trust
ClinicalTrials.gov Identifier:
NCT00816088
First received: December 30, 2008
Last updated: May 26, 2010
Last verified: August 2009
  Purpose

Fungal infections caused by Aspergillus fumigatus are now identified in up to 45% of patients dying from haematological malignancy. There has been a significant increase in deaths from IA over the last 20 years. Our current diagnostic approach is neither sensitive nor specific. The purpose of this study is to prospectively assess the value of current diagnostic tools, as well as test other new diagnostic methods for the diagnosis of IA among haemato-oncology patients undergoing chemotherapy or stem cell transplantation.


Condition
Invasive Aspergillosis
Neutropenia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Diagnostic and Management Strategies for Invasive Aspergillosis in Neutropenic Adult Haemato-Oncology Patients With a Proposal for Investigation of a Novel Potential Marker for Early Diagnosis: a Prospective Cohort Study

Resource links provided by NLM:


Further study details as provided by King's College Hospital NHS Trust:

Primary Outcome Measures:
  • To improve understanding of current clinical practice for diagnosis and management of IA. [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
  • To investigate and evaluate novel potential marker(s) for early diagnosis of Invasive Aspergillosis [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluation of established and experimental diagnostic methods [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
  • Costing analysis [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
  • Establish the prognostic value of CT appearances in patients with IA [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
  • Assessing the value of methylene blue 'tattooing' prior to surgical biopsy [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Seum, Whole blood, urine, broncho-alveolar lavage, tissue


Estimated Enrollment: 200
Study Start Date: December 2008
Estimated Study Completion Date: August 2011
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts
neutropenia
Patients undergoing stem cell transplantation or chemotherapy likely to lead to prolonged neutropenia.

  Hide Detailed Description

Detailed Description:

The basis of the diagnosis of invasive aspergillosis is usually based on radiological appearances, which are neither sensitive nor specific. The burden of this problem is also not properly documented and there is paucity of prospective data in the literature. Therefore, we want to prospectively collect complete epidemiological data on all our patients. In addition we want to collaborate with radiological, respiratory, and microbiological colleagues to develop a unified approach to diagnosis. In the initial 12−18 months of the study all adult haemato−oncology patients likely to be rendered neutropenic during their treatment will be enrolled. All clinical data will be collected including dose, duration, and side−effects of anti−fungals administered. We will evaluate accepted diagnostic modalities for IA including the determination of optimum cut−offs for galactomannan and B−D−glucan in serum and urine in this cohort. In addition we would investigate the utility of other approaches for the diagnosis of IA such as markers for tissue injury and cytokine profiling.

We would test the urine in parallel with blood for galactomannan and B−D glucan to assess its usefulness with respect to blood.

CT scanning forms an important cornerstone of our diagnostic workup currently. However, there is paucity of data on the natural history and spectrum of CT changes in neutropenic patients with IA. Thus, our aim is to carefully document such changes in our cohort. We aim to rationalise CT imaging in the following way:

  1. Baseline CT:

    We aim to perform an initial non−contrast enhanced thin−section continuous volume acquisition thoracic CT study on all the study patients. This will allow us to establish a "baseline" of normality in addition to potentially identifying those patients with pre−existing but indeterminate pulmonary lesions prior to chemotherapy or stem−cell transplantation.

  2. Diagnostic CT:

    Neutropaenic patients with febrile episodes that are unresponsive to standard second−line broad−spectrum antibiotics combination (currently meropenem and vancomycin) will be referred for a contrast−enhanced thin section continuous volume CT scan. The purpose of this CT study is primarily to support the clinical suspicion of a diagnosis of IA and to determine its morphological extent. The purpose of the contrast injection is to test the hypothesis that in patients with IA, regions of necrotic lung (in contrast to other "inflammatory" or infective lesions) should not demonstrate any contrast enhancement.

  3. Follow−up CTs (x2):

In patients with CT features of IA on the Diagnostic CT (see No. 2 above) and who have been commenced on antifungal chemotherapy, two follow−up, low−dose CTs (without iv contrast) will be performed at 10 days and 4 weeks after the diagnostic CT. These CT studies will not only allow us to evaluate the serial changes on CT but also determine the potential relationships between the initial CT features, haematological factors and outcome.

To increase the diagnostic yield, patients who are referred for lung biopsy, will undergo the technique of preoperative "labeling": small indeterminate lung nodules are frequently invisible and impalpable. There is an encouraging literature which indicates that preoperative labeling of lung lesions with a small (0.3−0.5ml) volume of methylene blue which acts a guidance track for the surgeon, may significantly improve the diagnostic yield from surgical (open or video−assisted thoracoscopic) biopsy.

Transplant patients typically would have 2−4 cycles of chemotherapy prior to admission for transplant. As such they have more chance of developing neutropenic infection and IA. Therefore we would perform a baseline bronchoscopy and washing (BAL) to assess the cytokine profile at admission and ensure that no infection is apparent before the initiation of transplant conditioning. A small amount of the BAL sample would be frozen and stored for future studies. Additional bronchoscopy may be done later during admission for both transplant and non-transplant patients if the clinical situation warrants it according to our current clinical practice.

Management strategies would also be assessed prospectively to evaluate the role of both prophylaxis and treatment. We are currently using itraconazole as our prophylactic agent of choice. Serum itraconazole levels will be measured on a weekly basis in all patients to ensure therapeutic levels are achieved.

We will be conducting costing analysis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Haemato-oncology patients undergoing high dose chemotherapy or stem cell transplantation likely to render them neutropenic.

Criteria

Inclusion Criteria:

  • All adult haemato-oncology patients admitted for transplant or high dose chemotherapy and able to consent.

Exclusion Criteria:

  • children (< 18 years old) or inability or refusal to consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00816088

Contacts
Contact: M. Mansour Ceesay, FRCPath +44 20 3299 9000 ext 4642 mansour.ceesay@kch.nhs.uk
Contact: Antonio Pagliuca, FRCPath +44 20 3299 3709 ext 3709 tony.pagliuca@kch.nhs.uk

Locations
United Kingdom
King's College Hospital NHS Foundation Trust Recruiting
London, United Kingdom, SE5 9RS
Principal Investigator: Antonio Pagliuca, FRCPath         
Principal Investigator: M. Mansour Ceesay, FRCPath         
Sponsors and Collaborators
King's College Hospital NHS Trust
Investigators
Principal Investigator: M.Mansour Ceesay, FRCPath Kings College Hospital
Principal Investigator: Antonio Pagliuca, FRCPath Kings College Hospital
Principal Investigator: Jim Wade, FRCPath Kings College Hospital
Principal Investigator: Melvyn Smith, PhD Kings College Hospital
Principal Investigator: Sujal Desai, FRCR Kings College Hospital
  More Information

No publications provided by King's College Hospital NHS Trust

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Wendy Fisher, King's College Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00816088     History of Changes
Other Study ID Numbers: 08/H0808/154, 08HA11
Study First Received: December 30, 2008
Last Updated: May 26, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by King's College Hospital NHS Trust:
chemotherapy
Stem cell transplantation

Additional relevant MeSH terms:
Aspergillosis
Neutropenia
Mycoses
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases

ClinicalTrials.gov processed this record on July 10, 2014