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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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ClinicalTrials.gov Identifier: NCT00361517
Recruitment Status : Completed
First Posted : August 8, 2006
Last Update Posted : September 26, 2018
Sponsor:
Collaborator:
National University Hospital, Singapore
Information provided by:
Singapore General Hospital

Tracking Information
First Submitted Date  ICMJE August 6, 2006
First Posted Date  ICMJE August 8, 2006
Last Update Posted Date September 26, 2018
Study Start Date  ICMJE June 1, 2006
Actual Primary Completion Date October 30, 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 8, 2009)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 6, 2006)
Development of proven or probable invasive fungal infection, fungal related mortality and overall survival in an intention to treat basis.
Change History Complete list of historical versions of study NCT00361517 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2009)
Duration of antifungal therapy and toxicity associated with antifungal therapy. [ Time Frame: while patient is on follow-up. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2006)
Duration of antifungal therapy and toxicity associated with antifungal therapy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE To Determine Whether Galactomannan Test Will Help to Detect Fungal Infections Early and Hence Start Treatment Early
Official Title  ICMJE 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Aspergillosis
Intervention  ICMJE
  • Behavioral: Galactomannan antigen monitoring, Aspergillus PCR
    There will be blood draws twice weekly for monitoring GM antigen and once a week for Aspergillus PCR.
  • Other: blood draws
    Blood is drawn for monitoring of Galactomannan antigen in the blood
  • Other: blood draws for GM monitoring
    blood samples will be taken twice weekly for monitoring of GM antigen levels in the blood and once a week for Aspergillus PCR.
  • Drug: Amphotericin-B deoxycholate
    1-1.5mg/kg, i.v, once a day
    Other Name: Fungizone, Abelcet, AmBisome, Fungisome, Amphocil,
  • Other: blood test
    Blood will be tested twice a week for the presence of Galactomannan.
  • Other: Blood test
    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)
Study Arms  ICMJE
  • Experimental: GM test
    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.
    Interventions:
    • Behavioral: Galactomannan antigen monitoring, Aspergillus PCR
    • Other: blood draws
    • Other: blood draws for GM monitoring
    • Drug: Amphotericin-B deoxycholate
    • Other: blood test
    • Other: Blood test
  • No Intervention: no GM monitoring
    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.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 23, 2009)
47
Original Enrollment  ICMJE
 (submitted: August 6, 2006)
180
Actual Study Completion Date  ICMJE June 30, 2009
Actual Primary Completion Date October 30, 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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
  2. 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
  3. Patients with severe aplastic anemia (SAA) receiving chemotherapy or immunosuppressive therapy using antithymocyte globulin
  4. Patients receiving allogeneic/autologous hematopoeitic stem cell transplant (HSCT) using myeloablative conditioning regimens
  5. Patients are at least 12 years of age, with Karnofsky score of 70%.?
  6. 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:

  1. Patients who are human immunodeficiency virus (HIV) infected
  2. Patients with uncontrolled bacteremia or active pulmonary infection at the time of randomisation
  3. 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].
  4. Patients receiving concomitant piperacillin/tazobactam or co-amoxyclavulinic acid
  5. Patients on palliative chemotherapy
  6. Patients with history of allergy to triazoles
  7. Patients with prior history of anaphylactic reaction to conventional amphotericin B
  8. 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
  9. Patients with expected life-expectancy < 72 hours
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Singapore
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00361517
Other Study ID Numbers  ICMJE NMRC/0984/2005
IRB #291/2005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr Tan Ban Hock, Singapore General Hospital
Study Sponsor  ICMJE Singapore General Hospital
Collaborators  ICMJE National University Hospital, Singapore
Investigators  ICMJE
Principal Investigator: Ban H Tan, Dr Singapore General Hospital
PRS Account Singapore General Hospital
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP