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

Phase 3

Completed

• Conditions: Aspergillosis
• Interventions: Behavioral: Galactomannan antigen monitoring, Aspergillus PCR; Other: blood draws; Other: blood draws for GM monitoring; Drug: Amphotericin-B deoxycholate; Other: Blood test

• Registration Number: NCT00361517
• Lead Sponsor: Singapore General Hospital

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 Timeline

• Study Start: 2006-06-01
• Study First Submitted: 2006-08-06
• Study First Submitted QC: 2006-08-06
• Study First Posted: 2006-08-08
• Primary Completion: 2007-10-30
• Study Completion: 2009-06-30
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-24
• Last Update Posted: 2018-09-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GM test	blood draws	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.
GM test	blood draws for GM monitoring	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.
GM test	Blood 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.
GM test	Galactomannan antigen monitoring, Aspergillus PCR	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.
GM test	Amphotericin-B deoxycholate	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Duration of antifungal therapy and toxicity associated with antifungal therapy.	while patient is on follow-up.

Trial Locations

Locations (1)

Singapore General Hospital; 🇸🇬 Singapore, Singapore