The Impact of Fast Antimicrobial Sensitivity Testing Tools on Stewardship Antibiotic and Clinical Outcome (ACT-FAST)

Official title

The Impact of Fast Antimicrobial Sensitivity Testing Tools on Stewardship Antibiotic and Clinical Outcome: a Randomized Clinical Trial Within an Adaptive Platform Trial for Patients With Bloodstream Infections

Overview

The ACT-FAST study aims to compare commercially available Rapid Antimicrobial Susceptibility Testing (R-AST) tools with the current standard of care for patients with Bloodstream Infections (BSI). The primary objective is to evaluate whether "early targeted" antibiotic prescriptions, guided by these rapid tests, can improve antimicrobial stewardship and patient clinical outcomes. To facilitate the evaluation of various diagnostic tools-including those currently on the market and those emerging in the near future-this study utilizes an adaptive clinical trial platform. This flexible design allows for the continuous assessment of different R-AST technologies within a single master protocol, ensuring that the most effective diagnostic strategies are identified efficiently.

Detailed description

ACT-FAST is a multicenter, open-label, randomized, adaptive clinical trial designed as the first domain of a broader adaptive platform. The study evaluates the clinical and stewardship impact of "early targeted" antibiotic therapy guided by Rapid Antimicrobial Susceptibility Testing (R-AST) compared to standard empirical therapy in patients with suspected bloodstream infections (BSI).

The study population consists of patients with positive blood cultures for whom pathogen identification and susceptibility results are still pending. Participants are randomized into one of two diagnostic strategies:

* Experimental Arm: Blood cultures are processed using R-AST testing tools to provide rapid phenotypic or genotypic susceptibility data. * Standard of Care (SoC) Arm: Blood cultures are processed according to the standard laboratory diagnostic workflow of the participating center.

In both arms, results are communicated to the treating clinicians, who adjust antibiotic therapy based on their clinical judgment and routine practice. As an adaptive trial, the randomization ratios may be adjusted based on the number of active intervention arms. To ensure scientific rigor, outcome assessors remain blinded to the treatment allocation.

Patients are followed for a total of 28 days to assess clinical outcomes and antimicrobial stewardship objectives. The platform design allows for the integration of additional R-AST tools or interventions through future protocol amendments, ensuring the study remains at the forefront of diagnostic innovation.

Interventions

• Diagnostic test Diagnostic Test: Rapid Antimicrobial Susceptibility Testing (R-AST) guided Stewardship
  In patients randomized to the intervention arm, the test under evaluation will be performed by the Humanitas Core Lab on positive blood cultures. The test is expected to provide results in a certain amount of time. The Lab will notify the ID consultant as soon as the test provides the first result (even if partial). The ID physician is expected to revise the antibiotic therapy according to the identified species, guided by the tool.
• Diagnostic test Standard of Care (SOC)
  Patients will be managed as usual, which typically consists of receiving standard empirical antibiotics, according to the local prescribing policy, continued until the results of the routine standard AST protocol in current use. In any case, both arms have standard microbiology culture and susceptibility testing performed, according to standard laboratory procedures and current guidelines, with results typically available after 48-72 hours from a blood culture positive result (day 3).

Primary outcome measures

• Compare commercially available R-AST testing tools with the current standard of care in BSI patients [Time frame: 24 hours]

Eligibility criteria

Inclusion criteria

• Patients admitted to emergency department or hospitalized for any cause in participating hospitals with clinically suspected BSI and positive blood culture.
• At least 18 years of age.

Exclusion criteria

• Have previously taken part in this trial.
• Concurrently participating in the active phase of a study considered incompatible.
• Patient with severe or terminal disease with life expectancy shorter than 48 h.
• Have an existing directive to withhold life-sustaining treatment, in relation to antibiotic use.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Italy · 1 center

• Infectious Disease Unit - IRCCS Humanitas Research Hospital — Rozzano

Publications

• Angus DC, Berry S, Lewis RJ, Al-Beidh F, Arabi Y, van Bentum-Puijk W, Bhimani Z, Bonten M, Broglio K, Brunkhorst F, Cheng AC, Chiche JD, De Jong M, Detry M, Goossens H, Gordon A, Green C, Higgins AM, Hullegie SJ, Kruger P, Lamontagne F, Litton E, Marshall J, McGlothlin A, McGuinness S, Mouncey P, Murthy S, Nichol A, O'Neill GK, Parke R, Parker J, Rohde G, Rowan K, Turner A, Young P, Derde L, McArt PMID 32267771
• Marquet K, Liesenborgs A, Bergs J, Vleugels A, Claes N. Incidence and outcome of inappropriate in-hospital empiric antibiotics for severe infection: a systematic review and meta-analysis. Crit Care. 2015 Feb 16;19(1):63. doi: 10.1186/s13054-015-0795-y. PMID 25888181
• Mettler J, Simcock M, Sendi P, Widmer AF, Bingisser R, Battegay M, Fluckiger U, Bassetti S. Empirical use of antibiotics and adjustment of empirical antibiotic therapies in a university hospital: a prospective observational study. BMC Infect Dis. 2007 Mar 26;7:21. doi: 10.1186/1471-2334-7-21. PMID 17386104
• Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP, Lamm W, Clark C, MacFarquhar J, Walton AL, Reller LB, Sexton DJ. Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med. 2002 Nov 19;137(10):791-7. doi: 10.7326/0003-4819-137-10-200211190-00007. PMID 12435215
• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, PMID 34599691
• Proschan M, Evans S. Resist the Temptation of Response-Adaptive Randomization. Clin Infect Dis. 2020 Dec 31;71(11):3002-3004. doi: 10.1093/cid/ciaa334. PMID 32222766
• Lin J, Bunn V. Comparison of multi-arm multi-stage design and adaptive randomization in platform clinical trials. Contemp Clin Trials. 2017 Mar;54:48-59. doi: 10.1016/j.cct.2017.01.003. Epub 2017 Jan 13. PMID 28089763
• Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, Holmes J, Mander AP, Odondi L, Sydes MR, Villar SS, Wason JMS, Weir CJ, Wheeler GM, Yap C, Jaki T. Adaptive designs in clinical trials: why use them, and how to run and report them. BMC Med. 2018 Feb 28;16(1):29. doi: 10.1186/s12916-018-1017-7. PMID 29490655

Identifiers

NCT: NCT07491419 · ACT-FAST

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗