Protocol and statistical analysis plan for the Antibiotic Choice On ReNal outcomes (ACORN) randomised clinical trial

Qian, Edward T; Casey, Jonathan D; Wright, Adam; Wang, Li; Siemann, Justin K.; Dear, Mary Lynn; Stollings, Joanna L.; Lloyd, Bradley D.; Seitz, Kevin P.; Nelson, George E.; Wright, Patty W.; Siew, Edward D.; Dennis, Bradley M.; Wrenn, Jesse O.; Andereck, Jonathan; Self, Wesley H.; Semler, Matthew W.; Rice, Todd W.

doi:10.1136/bmjopen-2022-066995

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References 39 publications

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“…The trial was initiated by the investigators, approved by the institutional review board with a waiver of informed consent, registered before enrollment commenced, and overseen by an independent data and safety monitoring board. The trial protocol and statistical analysis plan were published before enrollment concluded and appear in Supplement 1.…”

Section: Methodsmentioning

confidence: 99%

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Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection

Qian,

Casey,

Wright

et al. 2023

JAMA

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ImportanceCefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial.ObjectiveTo determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction.Design, Setting, and ParticipantsThe Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022.InterventionsPatients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam.Main Outcomes and MeasuresThe primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days.ResultsThere were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, −1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]).Conclusions and RelevanceAmong hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction.Trial RegistrationClinicalTrials.gov Identifier: NCT05094154

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Section: Methodsmentioning

confidence: 99%

“…Details regarding the sample size estimation and reestimation have been reported previously . The trial was initially designed to enroll 2050 patients to provide 80% statistical power to detect an odds ratio (OR) of 0.65 in the primary analysis (eMethods in Supplement 2).…”

Section: Methodsmentioning

confidence: 99%