"Micafungin as Effective as Liposomal Amphotericin B in Children With Invasive Candidiasis or Candidaemia: Presented at ECCMID-ICC"
By Chris Berrie
MUNICH, GERMANY -- April 2, 2007 -- The antifungal micafungin is as effective as liposomal amphotericin B (AmBisome(R); L-AmB) for treated children and adolescents with candidaemia or invasive candidiasis, irrespective of neutropenic status, according to results from a large, multicentre, double-blind, randomised, paediatric study.
However, the researchers report, micafungin treatment showed a tendency to fewer treatment-related adverse events, and near significance for fewer discontinuations due to adverse events.
The findings were presented here on April 1[st at the joint 17th European Congress of Clinical Microbiology and Infectious Diseases and 25th International Congress of Chemotherapy (ECCMID-ICC).
The study was designed to compare the efficacy and safety of micafungin and L-AmB in paediatric patients with candidaemia or invasive candidiasis, said principal investigator Antonio Arrieta, MD, director of infectious diseases, Children's Hospital of Orange County, Orange, United States.
"The inclusion criteria were such that they could allow for patients who were neutropenic or not neutropenic, and for children under 15 years of age who had confirmed diagnosis of candidaemia or invasive candidiasis," Dr. Arrieta said.
The overall treatment success was based on clinical and mycological response at the end of therapy, with monitoring of adverse events for safety analysis.
After 106 patients were randomised, the intention-to-treat (ITT) population all received at least 1 dose of medication. Fifty-two patients with a mean age of 4.0 years received micafungin 2 mg/kg/day IV, and 54 with mean age of 2.2 years received L-AmB 3 mg/kg/day IV, for 2 to 4 weeks.
There was a further modified intent-to-treat population where patients received between 1 and 5 doses of medication, and finally the per-protocol set (PPS) who satisfied all criteria and had confirmed diagnosis of candidaemia (n = 41) or invasive candidiasis (n = 42).
Clinicians had the option to increase the doses to 4 mg/kg of micafungin or 5 mg/kg of L-AmB, Dr. Arrieta added. A 50% reduction in the dose of L-AmB was allowed for patients who developed nephrotoxicity.
All age groups, including prematurity at birth, were well represented, and well matched across the 2 treatment groups, but the researchers observe a difference in the number of neutropenic patients, although this difference did not reach statistical significance (12.2% in the micafungin group and 23.8% in the L-AmB group.
The 3 major underlying disorders were (PPS; micafungin vs L-AmB): haematological malignancy (19.5% vs 23.8%); prematurity at birth (22.0% vs 16.7%); and gastrointestinal disorder (22.0% vs 17.7%). The hospitalisation and risk categories at baseline generally showed a trend against the micafungin patients, in hospitalisation in ICU (58.5% vs 38.1%) and risk factors: intravenous line/ device (41.5% vs 26.2%); antibiotic use (31.7% vs 23.8%); corticosteroid therapy (26.8% vs 14.3%); other immunosuppressants (17.1% vs 21.4%), total parenteral nutrition (17.1% vs 9.5%); and others (26.8% vs 14.3%).
Most patients in both treatment groups had candidaemia (92.7% vs 95.2%) as opposed to invasive candidiasis, and about a third of each group had C. albicans as the infecting species (39.0% vs 33.3%). The full range of non-albicans Candida spp. identified included: C. parapsilosis (26.8% vs 33.3%); C. tropicalis (17.1% vs 19.0%); C. krusei (7.3% vs 0.0%); C. guilliermondii (4.9% vs 2.4%); C. lipolytica (2.4% vs 4.8%); and other non-albicans Candida spp. (4.9% vs 7.1%).
Treatment success rates across the 2 study arms were not significantly different (85.4% on micafungin and 88.1% on L-AmB), with similarity seen for treatment success according to neutropenic status (<500 cells/microL, 100.0% vs 90.0%; persistence of neutropenia, 1/1 patients vs 3/4 patients).
Analysis of treatment success by age group showed no significant differences, either between the 2 treatment groups or across increasing age groups: <4 weeks, 100.0% vs 80.0%; 4 weeks - <2 years, 77.8% vs 90.9%;2 - <12 years, 83.3% vs 84.6%; and 12 - <16 years, 100.0% vs 100.0%.
Finally, there were no significant differences in treatment success between C. albicans (93.8% vs 100.0%) and non-albicans (80.0% vs 82.1%), as was seen within the various non-albicans Candida spp. The same was the case for primary diagnosis (candidaemia, 86.6% vs 87.5%; invasive candidiasis, 66.7% vs 100.0%), and by mycological response (success, 87.8% vs 88.1%; success by eradication, 78.0% vs 83.3%; and persistent failure, 12.2% vs 11.9%).
The incidence of treatment-related adverse events in the ITT population were 36.5% for micafungin and 42.6% for L-AmB); serious adverse event rates were 3.8% and 9.3%, respectively. Neither of these differences reached significance. Fewer patients in the micafungin group discontinued therapy due to adverse events (3.8% vs 16.7%), and this difference almost reached significance (P = .052).
There were no differences in mortality rates, either in the overall group (n = 13, both treatment groups) or mortality attributable to fungal infection (n = 4, n = 3, respectively).
"The overall treatment success rates were high and comparable for micafungin and liposomal amphotericin B in paediatric patients with candidaemia or invasive candidiasis," Dr. Arrieta said.
Further, there was no difference between the 2 agents in terms of efficacy according to age or neutropenic status, and while both treatments were well tolerated, discontinuations due to adverse events almost reached significance in favour of micafungin.
This study was supported by Astellas Pharma.
[Presentation title: Micafungin versus Liposomal Amphotericin B (Ambisome(R)) in Paediatric Patients With Invasive Candidiasis or Candidaemia. Abstract O141]
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