AspergillosisPhase 3NCT00361517
To Determine Whether Galactomannan Test Will Help to Detect Fungal Infections Early and Hence Start Treatment Early
A Phase 3 study testing Galactomannan antigen monitoring, Aspergillus PCR, blood draws and blood draws for GM monitoring in people with Aspergillosis, run by Singapore General Hospital at 1 site in Singapore.
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Aspergillosis
- What is being tested?
- Galactomannan antigen monitoring, Aspergillus PCR, blood draws and blood draws for GM monitoring
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteSingapore
- Study dates
- 1 Jun 2006to 30 Jun 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the 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.
- Conditions
- Aspergillosis
- Being tested
- Galactomannan antigen monitoring, Aspergillus PCR, blood draws, blood draws for GM monitoring, Amphotericin-B deoxycholate, blood test
- Keywords
- GM monitoring, Immunocompromised, hematological disorder, Allogenic HSCT recipients, Aspergillus PCR assay
- Medical subject headings
- Aspergillosis, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Galactomannan antigen monitoring, Aspergillus PCRBehavioural
There will be blood draws twice weekly for monitoring GM antigen and once a week for Aspergillus PCR.
blood drawsOther
Blood is drawn for monitoring of Galactomannan antigen in the blood
blood draws for GM monitoringOther
blood samples will be taken twice weekly for monitoring of GM antigen levels in the blood and once a week for Aspergillus PCR.
Amphotericin-B deoxycholateDrug
Also called Fungizone, Abelcet, AmBisome, Fungisome, Amphocil,
1-1.5mg/kg, i.v, once a day
blood testOther
Blood will be tested twice a week for the presence of Galactomannan.
Blood testOther
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 group | Role | What they receive |
|---|---|---|
| GM test | Experimental | 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. Receives: Behavioral: Galactomannan antigen monitoring, Aspergillus PCR; Other: blood draws; Other: blood draws for GM monitoring; Drug: Amphotericin-B deoxycholate; Other: blood test |
| no GM monitoring | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of proven or probable invasive fungal infection, fungal related mortality and overall survival in an intention to treat basis.
Measured: During neutropenia, or, in HSCT patients, while under immunosuppressive therapy
Secondary outcomes (1)
Duration of antifungal therapy and toxicity associated with antifungal therapy.
Measured: while patient is on follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2006 (estimated)
- Study start1 Jun 2006
- Primary completion30 Oct 2007
- Study completion30 Jun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AspergillosisStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National University Hospital, Singapore
- Investigators
- Ban H Tan, Dr, Principal investigator, Singapore General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00361517
- Sponsor's protocol ID
- NMRC/0984/2005
- Other IDs
- IRB #291/2005
- Status last verified
- Sep 2018
- First submitted
- 6 Aug 2006
- Last updated
- 26 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 11170942Tan 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.
PubMed 21397541
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00361517
- Acronym / sponsor ID
- NMRC/0984/2005
- Conditions
- Aspergillosis
- Keywords
- GM monitoring, Immunocompromised, hematological disorder, Allogenic HSCT recipients, Aspergillus PCR assay
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Collaborators
- National University Hospital, Singapore
- Study start
- 1 Jun 2006
- Primary completion
- 30 Oct 2007 (actual)
- Study completion
- 30 Jun 2009 (actual)
- First posted
- 8 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GM test | Experimental | Behavioral: Galactomannan antigen monitoring, Aspergillus PCR, Other: blood draws, Other: blood draws for GM monitoring, Drug: Amphotericin-B deoxycholate, Other: blood testTwice 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. |
| no GM monitoring | No intervention | –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. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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%.?
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Galactomannan antigen monitoring, Aspergillus PCRThere will be blood draws twice weekly for monitoring GM antigen and once a week for Aspergillus PCR. | Behavioural | GM test |
| blood drawsBlood is drawn for monitoring of Galactomannan antigen in the blood | Other | GM test |
| blood draws for GM monitoringblood samples will be taken twice weekly for monitoring of GM antigen levels in the blood and once a week for Aspergillus PCR. | Other | GM test |
| Amphotericin-B deoxycholateAlso: Fungizone, Abelcet, AmBisome, Fungisome, Amphocil,1-1.5mg/kg, i.v, once a day | Drug | GM test |
| blood testBlood will be tested twice a week for the presence of Galactomannan. | Other | GM test |
| Blood testBlood 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) | Other | GM test |
Primary outcome
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
1 secondary outcome
Duration of antifungal therapy and toxicity associated with antifungal therapy.
Time frame: while patient is on follow-up.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2018.
- Background: PubMed 11170942Lin 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.
- Derived from this study: PubMed 21397541Tan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ban H Tan, Dr principal investigator
Singapore General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Galactomannan antigen monitoring, Aspergillus PCR, blood draws and blood draws for GM monitoring in people with Aspergillosis, run by Singapore General Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00361517, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2018.