Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial

Bart Jan Kullberg, Claudio Viscoli, Peter G. Pappas, Jose Vazquez, Luis Ostrosky-Zeichner, Coleman Rotstein, Jack D. Sobel, Raoul Herbrecht, Galia Rahav, Sutep Jaruratanasirikul, Ploenchan Chetchotisakd, Eric Van Wijngaerden, Jan De Waele, Christopher Lademacher, Marc Engelhardt, Laura Kovanda, Rodney Croos-Dabrera, Christine Fredericks, George R. Thompson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis. Methods: Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety. Results: Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3% of patients in the isavuconazole arm and 71.1% in the caspofungin arm (adjusted difference -10.8, 95% confidence interval -19.9 - 1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups. Conclusions: This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups. Clinical Trials Registration: NCT00413218.

Original languageEnglish (US)
Article numberciy827
Pages (from-to)1981-1989
Number of pages9
JournalClinical Infectious Diseases
Volume68
Issue number12
DOIs
StatePublished - Jun 2019

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caspofungin
Candidemia
Candida
Infection
Invasive Candidiasis
Therapeutics
Clinical Trials
Population
Safety
Mortality
isavuconazole

Keywords

  • Candida
  • caspofungin
  • isavuconazole
  • voriconazole

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Kullberg, B. J., Viscoli, C., Pappas, P. G., Vazquez, J., Ostrosky-Zeichner, L., Rotstein, C., ... Thompson, G. R. (2019). Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial. Clinical Infectious Diseases, 68(12), 1981-1989. [ciy827]. https://doi.org/10.1093/cid/ciy827

Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections : The ACTIVE Trial. / Kullberg, Bart Jan; Viscoli, Claudio; Pappas, Peter G.; Vazquez, Jose; Ostrosky-Zeichner, Luis; Rotstein, Coleman; Sobel, Jack D.; Herbrecht, Raoul; Rahav, Galia; Jaruratanasirikul, Sutep; Chetchotisakd, Ploenchan; Van Wijngaerden, Eric; De Waele, Jan; Lademacher, Christopher; Engelhardt, Marc; Kovanda, Laura; Croos-Dabrera, Rodney; Fredericks, Christine; Thompson, George R.

In: Clinical Infectious Diseases, Vol. 68, No. 12, ciy827, 06.2019, p. 1981-1989.

Research output: Contribution to journalArticle

Kullberg, BJ, Viscoli, C, Pappas, PG, Vazquez, J, Ostrosky-Zeichner, L, Rotstein, C, Sobel, JD, Herbrecht, R, Rahav, G, Jaruratanasirikul, S, Chetchotisakd, P, Van Wijngaerden, E, De Waele, J, Lademacher, C, Engelhardt, M, Kovanda, L, Croos-Dabrera, R, Fredericks, C & Thompson, GR 2019, 'Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial', Clinical Infectious Diseases, vol. 68, no. 12, ciy827, pp. 1981-1989. https://doi.org/10.1093/cid/ciy827
Kullberg, Bart Jan ; Viscoli, Claudio ; Pappas, Peter G. ; Vazquez, Jose ; Ostrosky-Zeichner, Luis ; Rotstein, Coleman ; Sobel, Jack D. ; Herbrecht, Raoul ; Rahav, Galia ; Jaruratanasirikul, Sutep ; Chetchotisakd, Ploenchan ; Van Wijngaerden, Eric ; De Waele, Jan ; Lademacher, Christopher ; Engelhardt, Marc ; Kovanda, Laura ; Croos-Dabrera, Rodney ; Fredericks, Christine ; Thompson, George R. / Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections : The ACTIVE Trial. In: Clinical Infectious Diseases. 2019 ; Vol. 68, No. 12. pp. 1981-1989.
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abstract = "Background: Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis. Methods: Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15{\%}. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety. Results: Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3{\%} of patients in the isavuconazole arm and 71.1{\%} in the caspofungin arm (adjusted difference -10.8, 95{\%} confidence interval -19.9 - 1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups. Conclusions: This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups. Clinical Trials Registration: NCT00413218.",
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AU - Pappas, Peter G.

AU - Vazquez, Jose

AU - Ostrosky-Zeichner, Luis

AU - Rotstein, Coleman

AU - Sobel, Jack D.

AU - Herbrecht, Raoul

AU - Rahav, Galia

AU - Jaruratanasirikul, Sutep

AU - Chetchotisakd, Ploenchan

AU - Van Wijngaerden, Eric

AU - De Waele, Jan

AU - Lademacher, Christopher

AU - Engelhardt, Marc

AU - Kovanda, Laura

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N2 - Background: Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis. Methods: Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety. Results: Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3% of patients in the isavuconazole arm and 71.1% in the caspofungin arm (adjusted difference -10.8, 95% confidence interval -19.9 - 1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups. Conclusions: This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups. Clinical Trials Registration: NCT00413218.

AB - Background: Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis. Methods: Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety. Results: Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3% of patients in the isavuconazole arm and 71.1% in the caspofungin arm (adjusted difference -10.8, 95% confidence interval -19.9 - 1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups. Conclusions: This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups. Clinical Trials Registration: NCT00413218.

KW - Candida

KW - caspofungin

KW - isavuconazole

KW - voriconazole

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