Clinical Trial: Validation of an Index of Neutropenia (D-index) in Febrile Neutropenic Cancer Patients
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: Empirical Antifungal Treatment in Neutropenic Patients Stratified by Risk: Prospective Validation of an Algorithm Based on the D-index
Brief Summary:
The main objective of this study is to test prospectively the performance of an algorithm stratified by an index based on neutrophil counts in association with galactomannan assay and image tests to start an antifungal early therapy (empirical/preemptive) in neutropenic patients. Ths specific objectives are to determine the overall incidence of invasive fungal infections, use of antifungal agents, duration of hospitalization and mortality in this cohort, and to evaluate if this strategy is associated with a reduction in the expected use of antifungal agents if a classical empiric antifungal strategy was used, without an increase in the incidence of invasive fungal infections.
This is a prospective, non randomized, non comparative study. Patients aged ≥ 18 years are eligible if they have acute leukemia, myelodysplasia or other baseline disease submitted to chemotherapy or to allogeneic stem cell transplantation with an expected duration of neutropenia (neutrophil count <500cells/mm³) of at least 10 days. Exclusion criteria are patients with and a past history of or invasive mold infection and those who do not want to participate. The study has no comparator arm. However, the investigators intend to determine if the algorithm based on the D-index would result in a 50% reduction in the use of antifungal agents, if all patients with persistent fever and neutropenia received empiric antifungal therapy. Based on our database of ~2,000 episodes of febrile neutropenia, 36% of patients had persistent fever between days 4 and 7 of antibiotics and would receive empiric antifungal therapy. A total of 105 patients will be needed to demonstrate a 50% reduction in antifungal use if the investigators compared this cohort with a matched control historical cohort (alpha = 5%, beta = 20%).
Detailed Summary:
Neutropenia is a major risk factor for invasive fungal infections, particularly those caused by moulds, such as Aspergillus spp., Fusarium spp. and the Zygomycetes. Among neutropenic patients, these invasive mould infections (IMI) occur almost exclusively in patients with profound neutropenia (<100 neutrophils/mm3) lasting more than 10-15 days [1-3]. Empiric antifungal therapy is considered standard of care in patients with persistent or recurrent fever and neutropenia. However using fever as the sole criterion for starting empiric therapy, a significant number of patients will receive antifungal therapy unnecessarily, particularly among recipients of fluconazole prophylaxis, because persistent fever in these patients is commonly due to various factors, such as uncontrolled occult bacterial infection, viral infection, drug fever and others [4].
An alternative to empiric antifungal therapy is the preemptive treatment. In this strategy, other markers (such as serology, radiology and clinical data) are added to persistent fever [5,6]. One problem of such strategy is that the biomarkers currently in use (galactomannan [GM], 1,3-beta-D-glucan and PCR) have high sensitivity. If one of these markers is used to trigger the start of antifungal therapy, still a considerable number of patients will use antifungal agents unnecessarily. However, a positive biomarker early in the course of neutropenia most likely represents a false-positive result. By contrast, a positive biomarker test late in the course of neutropenia is more likely to be a true positive. A problem is that no cutoff value of duration of neutropenia is validated to help clinicians to identify these 2 possibilities.
A clinical parameter that evaluated the dynamics of neutropenia, combining intensity and duration, could be a good tool to identify patients at high risk
Sponsor: Universidade Federal do Rio de Janeiro
Current Primary Outcome: Incidence of suspected and documented mold infection, use of anti mold therapy, duration of hospitalization and death rate. [ Time Frame: At the end of the episode of febrile neutropenia ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
Original Secondary Outcome:
Information By: Universidade Federal do Rio de Janeiro
Dates:
Date Received: September 22, 2009
Date Started: February 2010
Date Completion:
Last Updated: January 28, 2014
Last Verified: January 2014
