TY - JOUR
T1 - Biomarker-guided antibiotic duration for hospitalized patients with suspected sepsis. The ADAPT-Sepsis Randomized Clinical Trial
AU - Dark, Paul
AU - Hossain, Anower
AU - McAuley, Daniel F
AU - Brealey, David
AU - Carlson, Gordon
AU - Clayton, Jonathan C
AU - Felton, Timothy W
AU - Ghuman, Belinder K
AU - Gordon, Anthony C
AU - Hellyer, Thomas P
AU - Lone, Nazir I
AU - Manazar, Uzma
AU - Richards, Gillian
AU - McCullagh, Iain J
AU - McMullan, Ronan
AU - McNamee, James J
AU - McNeil, Hannah C
AU - Mouncey, Paul R
AU - Naisbitt, Micheal J
AU - Parker, Robert J
AU - Poole, Ruth L
AU - Rostron, Anthony J
AU - Singer, Mervyn
AU - Stevenson, Matt D
AU - Walsh, Tim S
AU - Welters, Ingeborg D
AU - Whitehouse, Tony
AU - Whiteley, Simon
AU - Wilson, Peter
AU - Young, Keith K
AU - Perkins, Gavin D
AU - Lall, Ranjit
AU - ADAPT-Sepsis Collaborators
PY - 2024/12/9
Y1 - 2024/12/9
N2 - IMPORTANCE: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain.OBJECTIVE: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.DESIGN, SETTING, AND PARTICIPANTS: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours.INTERVENTION: From January 1, 2018, to June 5, 2024, 918 patients were assigned to the daily PCT-guided protocol, 924 to the daily CRP-guided protocol, and 918 assigned to standard care.MAIN OUTCOMES AND MEASURES: The primary outcomes were total duration of antibiotics (effectiveness) and all-cause mortality (safety) to 28 days. Secondary outcomes included critical care unit data and hospital stay data. Ninety-day all-cause mortality was also collected.RESULTS: Among the randomized patients (mean age 60.2 [SD, 15.4] years; 60.3% males), there was a significant reduction in antibiotic duration from randomization to 28 days for those in the daily PCT-guided protocol compared with standard care (mean duration, 10.7 [SD, 7.6] days for standard care and 9.8 [SD, 7.2] days for PCT; mean difference, 0.88 days; 95% CI, 0.19 to 1.58, P = .01). For all-cause mortality up to 28 days, the daily PCT-guided protocol was noninferior to standard care, where the noninferiority margin was set at 5.4% (19.4% [170 of 878] of patients receiving standard care; 20.9% [184 of 879], PCT; absolute difference, 1.57; 95% CI, -2.18 to 5.32; P = .02). No difference was found in antibiotic duration for standard care vs daily CRP-guided protocol (mean duration, 10.6 [7.7] days for CRP; mean difference, 0.09; 95% CI, -0.60 to 0.79; P = .79). For all-cause mortality, the daily CRP-guided protocol was inconclusive compared with standard care (21.1% [184 of 874] for CRP; absolute difference, 1.69; 95% CI, -2.07 to 5.45; P = .03).CONCLUSIONS AND RELEVANCE: Care guided by measurement of PCT reduces antibiotic duration safely compared with standard care, but CRP does not. All-cause mortality for CRP was inconclusive.TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN47473244.
AB - IMPORTANCE: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain.OBJECTIVE: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.DESIGN, SETTING, AND PARTICIPANTS: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours.INTERVENTION: From January 1, 2018, to June 5, 2024, 918 patients were assigned to the daily PCT-guided protocol, 924 to the daily CRP-guided protocol, and 918 assigned to standard care.MAIN OUTCOMES AND MEASURES: The primary outcomes were total duration of antibiotics (effectiveness) and all-cause mortality (safety) to 28 days. Secondary outcomes included critical care unit data and hospital stay data. Ninety-day all-cause mortality was also collected.RESULTS: Among the randomized patients (mean age 60.2 [SD, 15.4] years; 60.3% males), there was a significant reduction in antibiotic duration from randomization to 28 days for those in the daily PCT-guided protocol compared with standard care (mean duration, 10.7 [SD, 7.6] days for standard care and 9.8 [SD, 7.2] days for PCT; mean difference, 0.88 days; 95% CI, 0.19 to 1.58, P = .01). For all-cause mortality up to 28 days, the daily PCT-guided protocol was noninferior to standard care, where the noninferiority margin was set at 5.4% (19.4% [170 of 878] of patients receiving standard care; 20.9% [184 of 879], PCT; absolute difference, 1.57; 95% CI, -2.18 to 5.32; P = .02). No difference was found in antibiotic duration for standard care vs daily CRP-guided protocol (mean duration, 10.6 [7.7] days for CRP; mean difference, 0.09; 95% CI, -0.60 to 0.79; P = .79). For all-cause mortality, the daily CRP-guided protocol was inconclusive compared with standard care (21.1% [184 of 874] for CRP; absolute difference, 1.69; 95% CI, -2.07 to 5.45; P = .03).CONCLUSIONS AND RELEVANCE: Care guided by measurement of PCT reduces antibiotic duration safely compared with standard care, but CRP does not. All-cause mortality for CRP was inconclusive.TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN47473244.
KW - antibiotic
KW - Biomarker-guided antibiotic duration
KW - sepsis
KW - hospitalized patients
U2 - 10.1001/jama.2024.26458
DO - 10.1001/jama.2024.26458
M3 - Article
C2 - 39652885
SN - 0098-7484
JO - JAMA
JF - JAMA
ER -