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To Determine Whether Galactomannan Test Will Help to Detect Fungal Infections Early and Hence Start Treatment Early

Primary Purpose

Aspergillosis

Status
Completed
Phase
Phase 3
Locations
Singapore
Study Type
Interventional
Intervention
Galactomannan antigen monitoring, Aspergillus PCR
blood draws
blood draws for GM monitoring
Amphotericin-B deoxycholate
blood test
Blood test
Sponsored by
Singapore General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Aspergillosis focused on measuring GM monitoring, Immunocompromised, hematological disorder, Allogenic HSCT recipients, Aspergillus PCR assay

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with newly diagnosed acute leukemia or high risk myelodysplastic syndrome (MDS) receiving induction chemotherapy with expected duration of neutropenia (absolute neutrophil count of < 500/mL) of at least 10 days Patients with relapsed acute leukemia or MDS receiving salvage chemotherapy with expected duration of neutropenia (absolute neutrophil count of < 500/mL) of at least 10 days Patients with severe aplastic anemia (SAA) receiving chemotherapy or immunosuppressive therapy using antithymocyte globulin Patients receiving allogeneic/autologous hematopoeitic stem cell transplant (HSCT) using myeloablative conditioning regimens Patients are at least 12 years of age, with Karnofsky score of 70%.? Patients on consolidation chemo regimens like HIDAC and HyperCVAD type B with expected duration of neutropenia (ANC < 500/ml) of at least 10 days Exclusion Criteria: Patients who are human immunodeficiency virus (HIV) infected Patients with uncontrolled bacteremia or active pulmonary infection at the time of randomisation Patients with pre-existing proven and probable invasive fungal infections, according to the definitions of the invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer; Mycoses Study Group of the National Institute of Allergy and Infectious Disease [10]. Patients receiving concomitant piperacillin/tazobactam or co-amoxyclavulinic acid Patients on palliative chemotherapy Patients with history of allergy to triazoles Patients with prior history of anaphylactic reaction to conventional amphotericin B Patients with serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or bilirubin more than 5 times the upper limit of normal or renal impairment with calculated creatinine clearance < 30ml/min Patients with expected life-expectancy < 72 hours

Sites / Locations

  • Singapore General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

GM test

no GM monitoring

Arm Description

Twice weekly blood draws from the patients in this arm for serial GM monitoring. They will be given standard antifungal prophylaxis but no antifungal therapy unless two consecutive GM readings are positive.

in this arm the patients will not have any GM monitoring and they will be given standard antifungal prophylaxis and treatment according to the published guidelines.

Outcomes

Primary Outcome Measures

Development of proven or probable invasive fungal infection, fungal related mortality and overall survival in an intention to treat basis.

Secondary Outcome Measures

Duration of antifungal therapy and toxicity associated with antifungal therapy.

Full Information

First Posted
August 6, 2006
Last Updated
September 24, 2018
Sponsor
Singapore General Hospital
Collaborators
National University Hospital, Singapore
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1. Study Identification

Unique Protocol Identification Number
NCT00361517
Brief Title
To Determine Whether Galactomannan Test Will Help to Detect Fungal Infections Early and Hence Start Treatment Early
Official Title
Using Serum Galactomannan Levels in a Prospective, Randomised, Non-blinded Trial to Guide Early Anti-fungal Therapy in Haematology Patients at Risk of Invasive Aspergillosis.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
June 1, 2006 (undefined)
Primary Completion Date
October 30, 2007 (Actual)
Study Completion Date
June 30, 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Singapore General Hospital
Collaborators
National University Hospital, Singapore

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Chemotherapy lowers the white blood cell count or weakens the immune system for a long time. This puts the patients at a high risk of getting a serious fungal infection of the internal organs or blood. One of these infections is caused by a mold called Aspergillus and can be life threatening. Usually doctors give preventive antifungal therapy to try to lower the risk of this infection. Despite this, patients are still at risk of getting fungal infection. This study is thus designed to test Galactomannan - a component of cell wall of Aspergillus and hence detect and treat fungal infection early.
Detailed Description
The diagnosis of invasive Aspergillosis (IA) remains a challenge in the febrile neutropenic and the hematopoietic stem cell transplant (HSCT) recipients. Recent studies have shown that early diagnosis of IA is possible in this group of high-risk patients. Serial screening of circulating Galactomannan (GM), an epitopic determinant of several antigens secreted by the Aspergillus early in its growth, has been shown to be sensitive and specific in the diagnosis of IA. This test may help us to detect IA early, thereby permitting a pre-emptive strategy to be initiated in high-risk patients. In a prospective, randomized, non-blinded study, we seek to compare the outcome of a novel GM-guided anti-fungal strategy against the conventional empirical antifungal therapy. Patients randomized to the conventional arm will not undergo serial GM monitoring, but will receive standard anti-fungal prophylaxis and standard empirical antifungal therapy in accordance with published guidelines. Patients randomized to the GM arm will receive standard anti-fungal prophylaxis but will not receive empiric anti-fungal therapy unless 2 GM readings are positive. The study aims to determine if such a strategy permits targeted, pre-emptive therapy in those at greatest risk, and spare febrile patients without evidence of fungal infection other than prolonged fever from unnecessary and potentially toxic therapy. It also aims to determine if GM guided pre-emptive antifungal therapy using Amphotericin-B deoxycholate prevents the development of proven or probable invasive aspergillosis (IA). The study will also prospectively evaluate (in a blinded fashion) the use of realtime polymerase chain reaction (RT PCR) assay in the same cohort of patients receiving GM serial monitoring, and investigate its role in the diagnosis and treatment monitoring of invasive Aspergillosis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aspergillosis
Keywords
GM monitoring, Immunocompromised, hematological disorder, Allogenic HSCT recipients, Aspergillus PCR assay

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GM test
Arm Type
Experimental
Arm Description
Twice weekly blood draws from the patients in this arm for serial GM monitoring. They will be given standard antifungal prophylaxis but no antifungal therapy unless two consecutive GM readings are positive.
Arm Title
no GM monitoring
Arm Type
No Intervention
Arm Description
in this arm the patients will not have any GM monitoring and they will be given standard antifungal prophylaxis and treatment according to the published guidelines.
Intervention Type
Behavioral
Intervention Name(s)
Galactomannan antigen monitoring, Aspergillus PCR
Intervention Description
There will be blood draws twice weekly for monitoring GM antigen and once a week for Aspergillus PCR.
Intervention Type
Other
Intervention Name(s)
blood draws
Intervention Description
Blood is drawn for monitoring of Galactomannan antigen in the blood
Intervention Type
Other
Intervention Name(s)
blood draws for GM monitoring
Intervention Description
blood samples will be taken twice weekly for monitoring of GM antigen levels in the blood and once a week for Aspergillus PCR.
Intervention Type
Drug
Intervention Name(s)
Amphotericin-B deoxycholate
Other Intervention Name(s)
Fungizone, Abelcet, AmBisome, Fungisome, Amphocil,
Intervention Description
1-1.5mg/kg, i.v, once a day
Intervention Type
Other
Intervention Name(s)
blood test
Intervention Description
Blood will be tested twice a week for the presence of Galactomannan.
Intervention Type
Other
Intervention Name(s)
Blood test
Intervention Description
Blood will be drawn twice a week and it will be tested for the presence of GM(a component of the cell wall of the mold Aspergillus which is released during growth)
Primary Outcome Measure Information:
Title
Development of proven or probable invasive fungal infection, fungal related mortality and overall survival in an intention to treat basis.
Time Frame
During neutropenia, or, in HSCT patients, while under immunosuppressive therapy
Secondary Outcome Measure Information:
Title
Duration of antifungal therapy and toxicity associated with antifungal therapy.
Time Frame
while patient is on follow-up.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with newly diagnosed acute leukemia or high risk myelodysplastic syndrome (MDS) receiving induction chemotherapy with expected duration of neutropenia (absolute neutrophil count of < 500/mL) of at least 10 days Patients with relapsed acute leukemia or MDS receiving salvage chemotherapy with expected duration of neutropenia (absolute neutrophil count of < 500/mL) of at least 10 days Patients with severe aplastic anemia (SAA) receiving chemotherapy or immunosuppressive therapy using antithymocyte globulin Patients receiving allogeneic/autologous hematopoeitic stem cell transplant (HSCT) using myeloablative conditioning regimens Patients are at least 12 years of age, with Karnofsky score of 70%.? Patients on consolidation chemo regimens like HIDAC and HyperCVAD type B with expected duration of neutropenia (ANC < 500/ml) of at least 10 days Exclusion Criteria: Patients who are human immunodeficiency virus (HIV) infected Patients with uncontrolled bacteremia or active pulmonary infection at the time of randomisation Patients with pre-existing proven and probable invasive fungal infections, according to the definitions of the invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer; Mycoses Study Group of the National Institute of Allergy and Infectious Disease [10]. Patients receiving concomitant piperacillin/tazobactam or co-amoxyclavulinic acid Patients on palliative chemotherapy Patients with history of allergy to triazoles Patients with prior history of anaphylactic reaction to conventional amphotericin B Patients with serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or bilirubin more than 5 times the upper limit of normal or renal impairment with calculated creatinine clearance < 30ml/min Patients with expected life-expectancy < 72 hours
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ban H Tan, Dr
Organizational Affiliation
Singapore General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Singapore General Hospital
City
Singapore
ZIP/Postal Code
169608
Country
Singapore

12. IPD Sharing Statement

Citations:
PubMed Identifier
11170942
Citation
Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001 Feb 1;32(3):358-66. doi: 10.1086/318483. Epub 2001 Jan 26.
Results Reference
background
PubMed Identifier
21397541
Citation
Tan BH, Low JG, Chlebicka NL, Kurup A, Cheah FK, Lin RT, Goh YT, Wong GC. Galactomannan-guided preemptive vs. empirical antifungals in the persistently febrile neutropenic patient: a prospective randomized study. Int J Infect Dis. 2011 May;15(5):e350-6. doi: 10.1016/j.ijid.2011.01.011. Epub 2011 Mar 11.
Results Reference
derived

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To Determine Whether Galactomannan Test Will Help to Detect Fungal Infections Early and Hence Start Treatment Early

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