Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00361517
Other study ID # NMRC/0984/2005
Secondary ID IRB #291/2005
Status Completed
Phase Phase 3
First received
Last updated
Start date June 1, 2006
Est. completion date June 30, 2009

Study information

Verified date September 2018
Source Singapore General Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 47
Est. completion date June 30, 2009
Est. primary completion date October 30, 2007
Accepts healthy volunteers No
Gender All
Age group 12 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

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
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:
blood test
Blood will be tested twice a week for the presence of Galactomannan.
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)

Locations

Country Name City State
Singapore Singapore General Hospital Singapore

Sponsors (2)

Lead Sponsor Collaborator
Singapore General Hospital National University Hospital, Singapore

Country where clinical trial is conducted

Singapore, 

References & Publications (1)

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. Epub 2001 Jan 26. Review. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Development of proven or probable invasive fungal infection, fungal related mortality and overall survival in an intention to treat basis. During neutropenia, or, in HSCT patients, while under immunosuppressive therapy
Secondary Duration of antifungal therapy and toxicity associated with antifungal therapy. while patient is on follow-up.
See also
  Status Clinical Trial Phase
Suspended NCT01887457 - Individualisation of Voriconazole Antifungal Therapy Antifungal Therapy Phase 2
Completed NCT00940017 - A Study To Assess The Anidulafungin And Voriconazole Concentration In Lung Following Intravenous Administration In Healthy Subjects Phase 4
Enrolling by invitation NCT01617759 - Aspergillus-specific PCR Assay in Cerebrospinal Fluid Samples for Detection of Central Nervous System Aspergillosis
Terminated NCT03905447 - The Effect of Early Treatment of PC945 on Aspergillus Fumigatus Lung Infection in Lung Transplant Patients. Phase 2
Recruiting NCT04744454 - Post Marketing Surveillance (PMS) Study of Cresemba in Korea.
Completed NCT02715570 - A Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of PC945 Phase 1
Withdrawn NCT01622595 - UARK 2009-99 A Non-interventional Observational Study of Infectious Complications in Cancer Patients N/A
Completed NCT00001937 - Comparing the Effectiveness of Fluconazole and a New Medicine (FK463) in Preventing Fungal Infections in Bone Marrow Transplant Patients Phase 3
Completed NCT04935463 - Mucormycosis in COVID-19
Withdrawn NCT01188759 - Voriconazole And Anidulafungin Combination For Invasive Aspergillosis In Pediatric Subjects Phase 3
Completed NCT00473252 - Surveillance of Fungal Infections During Construction Activity N/A
Completed NCT00037206 - A Safety & Effectiveness Study of Intravenous Anidulafungin With AmBisome® for Treatment of Invasive Aspergillosis (IA). Phase 2/Phase 3
Completed NCT04818853 - COVID-19 Associated Pulmonary Aspergillosis (CAPA) and Other Invasive Fungal Infections (IFI)
Completed NCT00412893 - Isavuconazole (BAL8557) for Primary Treatment of Invasive Aspergillosis Phase 3
Recruiting NCT06135597 - Immune Regulation in Chronic Aspergillus Infection After COVID-19 Infection
Terminated NCT02646800 - Post Marketing Study to Evaluate the Safety and Efficacy of Micafungin Against Fungal Infections Caused by Candida Spp or Aspergillus Spp Phase 4
Completed NCT00854607 - An Observational Study of Fungal Biomarkers (MK-0000-089) N/A
Completed NCT00388167 - Acetato de Caspofungin (Cancidas®) in the Treatment of Fungal Infection Phase 4
Completed NCT05065658 - Posaconazole Prophylaxis for CAPA Prevention in Critically-Ill Patients
Completed NCT00005912 - Voriconazole to Prevent Systemic Fungal Infections in Children Phase 1