Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial

Maertens, Johan; Raad, Issam; Marr, Kieren A.; Patterson, Thomas F.; Kontoyiannis, Dimitrios P.; Cornely, Oliver A.; Bow, Eric J.; Rahav, Galia; Neofytos, Dionysios; Aoun, Mickaël; Baddley, John W.; Giladi, Michael; Heinz, Werner; Herbrecht, Raoul; Hope, William; Karthaus, Meinolf; Lee, Dong Gun; Lortholary, Olivier; Morrison, Vicki A.; Oren, Ilana; Selleslag, Dominik; Shoham, Shmuel; Thompson, George R.; Lee, Misun; Maher, Rochelle; Schmitt‐Hoffmann, Anne; Zeiher, Bernhardt; Ullmann, Andrew J.

doi:10.1016/s0140-6736(15)01159-9

Cited by 774 publications

(841 citation statements)

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“…No consideration was given to the endpoints of this analysis when the sample size was determined for this trial. The sample-size calculation conducted for the SECURE trial was based on a non-inferiority design with a primary trial endpoint of all-cause mortality through Day 42 17 . Approximately 255 patients per group were to be enrolled to ensure at least 80% power to demonstrate that the upper bound of the 95% confidence interval (CI) for a treatment difference in favor of the comparator was no larger than 10%.…”

Section: Resultsmentioning

confidence: 99%

“…Patient risk factors and underlying illnesses were well balanced in the SECURE trial 17 . Similar numbers of patients in the treatment arms had proven/probable disease (isavuconazole, n ¼ 143; voriconazole, n ¼ 129), and a similar distribution of pathogens was observed, with 49/143 (34%) vs 39/129 (30%) having infections caused by Aspergillus spp.…”

Section: Discussionmentioning

confidence: 98%

“…Written, informed consent was obtained from all individual participants (or legally-authorized representatives) included in the study. The study design, treatment regimen, and patient population have been described previously (see Figure 1) 17 .…”

Section: Study Overviewmentioning

confidence: 99%

“…Of these, up to 501 patients had sufficient hospital details for calculation of analysis endpoints (isavuconazole, n ¼ 246; voriconazole, n ¼ 255). Baseline demographics and risk factors for fungal infections of the patients were balanced between the two treatment groups 17 . Overall, 433 (83.9%) patients in the ITT population had hematological malignancy, 360 (69.8%) had active malignancy, and 105 (20.3%) patients had received a prior allogeneic bone marrow transplant.…”

Section: Patientsmentioning

confidence: 99%

“…In the phase III SECURE trial, isavuconazole was shown to be non-inferior to voriconazole for all-cause mortality through Day 42 (19% vs 20%, respectively) for the primary treatment of IMD 17 . Isavuconazole was also well tolerated compared with voriconazole, with statistically significantly fewer drugrelated adverse events, particularly skin, eye, and hepatobiliary disorders.…”

Section: Introductionmentioning

confidence: 99%

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Hospital resource use of patients receiving isavuconazole vs voriconazole for invasive mold infections in the phase III SECURE trial

Horn

Goff

Khandelwal

et al. 2016

Journal of Medical Economics

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Objective: In the phase III SECURE trial, isavuconazole was non-inferior to voriconazole for all-cause mortality for the primary treatment of invasive mold disease (IMD) caused by Aspergillus spp. and other filamentous fungi. This analysis assessed whether hospital resource utilization was different between patients treated with isavuconazole vs voriconazole in SECURE. Methods: The analysis population comprised adults with proven/probable/possible IMD enrolled in SECURE. The primary endpoint was hospital length of stay (LOS) in the overall trial population. Patients were also stratified by estimated glomerular filtration rate-modification of diet in renal disease category (< 60 mL/min/ Median LOS was shorter, but not significantly, in patients with a BMI !30 kg/m 2 (isavuconazole 13.5 days vs voriconazole 22 days; HR ¼ 1.57; 95% CI ¼ 0.70-3.52) or aged >65 years (isavuconazole 15.0 days vs voriconazole 20.0 days; HR ¼ 1.37; 95% CI ¼ 0.87-2.16). Limitations: As the patient subgroups analyzed were small, sub-group findings should be interpreted with caution in light of the lack of statistical significance for each sub-group-by-treatment interaction. Conclusions: Isavuconazole may reduce hospital LOS in certain subgroups of patients with IMD, especially those with moderate-to-severe renal impairment. ARTICLE HISTORY

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Section: Study Overviewmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hospital resource use of patients receiving isavuconazole vs voriconazole for invasive mold infections in the phase III SECURE trial

Horn

Goff

Khandelwal

et al. 2016

Journal of Medical Economics

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Antifungal Drugs

Seyedmousavi

2021

Burger's Medicinal Chemistry and Drug Discovery

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Invasive fungal infections are considered an expanding public health threat, worldwide. Annually, over one billion people are estimated to suffer from fungal infections and/or allergies originating from opportunistic and pathogenic fungi. Fungal diseases also kill more than 1.5 million each year. Antifungal therapy is a central component in the management of life‐threatening fungal infections. However, only few classes of FDA‐approved antifungal agents are available for therapy, which have limited efficacy, particularly in the treatment of disseminated and emerging fungal infections. These drugs include polyenes, azoles, echinocandins, and the nucleoside analogs. Depending on the strategy chosen, monotherapy and/or combination antifungal drugs can be used based on the clinical picture and the species identification of the etiologic agent. The use of antifungal drugs in the therapy of fungal diseases can lead to the development of resistance. Of note, some organisms are inherently resistant to these antifungal agents. This chapter focuses on the currently available classes of systemic antifungal drugs in clinical use, innovative strategies in reformulation and delivery of available drugs, development of new agents of known antifungal drug classes, and new drugs of synthetic antifungal drugs under preclinical and clinical investigations. We further discuss the currently available evidence for the emergence of fungal resistance against these agents.

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Aspergillus , Talaromyces , and Penicillium

Chen,

Meyer,

Sorrell

et al. 2023

ClinMicroNow

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The genus Aspergillus is classified in the family Trichocomaceae of the Ascomycota. The majority of human infections due to known Aspergillus species are caused by A. fumigatus , followed by A. flavus , A. terreus , and A. niger , with recognition that these designations represent complexes of closely related species. Aspergillus species are environmental saprophytes that thrive in decaying vegetation and are readily cultured from soil, water, certain foods, and air. Aspergillus DNA can be detected in clinical specimens either by nucleic acid amplification methods specifically targeting Aspergillus or by panfungal PCR assays followed by DNA sequencing for species identification. Penicillium sensu lato is associated with two teleomorphic genera: Eupenicillium and Talaromyces . Assays have been developed to detect antibodies to Talaromyces marneffei , Talaromyces marneffei antigen, or both in serum and other body fluids in various test formats, including immunodiffusion, indirect immunofluorescence, and enzyme‐linked immunosorbent assay.

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Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial

Cited by 774 publications

References 28 publications

Hospital resource use of patients receiving isavuconazole vs voriconazole for invasive mold infections in the phase III SECURE trial

Hospital resource use of patients receiving isavuconazole vs voriconazole for invasive mold infections in the phase III SECURE trial

Antifungal Drugs

Aspergillus , Talaromyces , and Penicillium

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