Effect of Antibiotic Choice On ReNal Outcomes (ACORN)

NCT05094154 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 210591
• Study Type: interventional
• Target: 2,634
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is one of the most common causes of acute illness and death in the United States. Early, empiric broad-spectrum antibiotics are a mainstay of sepsis treatment. Two classes of antibiotics with activity against Pseudomonas, anti-pseudomonal cephalosporins and anti-pseudomonal penicillins, are commonly used for acutely ill adults with sepsis in current practice. Recent observational studies, however, have raised concern that anti-pseudomonal penicillins may cause renal toxicity. Anti-pseudomonal cephalosporins, by comparison, may be associated with a risk of neurotoxicity. Rigorous, prospective data regarding the comparative effectiveness and toxicity of these two classes of medications among acutely ill patients are lacking. The investigator propose a randomized trial comparing the impact of anti-pseudomonal cephalosporins and anti-pseudomonal penicillins on renal outcomes of acutely ill patients.

Conditions

Sepsis; AKI; Neurotoxicity

Outcome Measures

Primary Outcomes (1)

• Acute Kidney Injury (AKI) Ordinal Scale

  Acute Kidney Injury Score between randomization and day 14. The acute kidney injury score is an ordinal outcome containing the stages of AKI as defined by Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria, new renal replacement therapy (RRT), and death: 0 = No AKI 1. = Stage 1 AKI (Creatinine increase by 1.5-1.9 times baseline OR increase by \>= 0.3 mg/dL) 2. = Stage 2 AKI (Creatinine increase by 2.0-2.9 times baseline) 3. = Stage 3 AKI (Creatinine increase by \>= 3.0 times baseline OR increase to \>= 4.0 mg/dL OR New RRT) 4. = Death

  14 days post-enrollment

Secondary Outcomes (2)

• Major Adverse Kidney Events Within 14 Days (MAKE14)

  14 days post-enrollment

• Delirium and Coma-Free Days to Day 14

  14 days post-enrollment

Other Outcomes (1)

• Post-Emergency Department Disposition

  14 days post-enrollment

Study Arms (2)

anti-pseudomonal cephalosporin

ACTIVE COMPARATOR

Participants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin.

Drug: anti-pseudomonal cephalosporin

anti-pseudomonal penicillin

ACTIVE COMPARATOR

Participants in the anti-pseudomonal penicillin arm will receive at least one dose of an anti-pseudomonal penicillin.

Drug: anti-pseudomonal penicillin

Interventions

anti-pseudomonal cephalosporin DRUG

Providers will be prompted to order an anti-pseudomonal cephalosporin, such as cefepime with a dose range of 500 mg, 1,000 mg, or 2,000 mg, and frequency every 6, 8, 12, or 24 hours based on provider discretion.

anti-pseudomonal cephalosporin

anti-pseudomonal penicillin DRUG

Providers will be prompted to order anti-pseudomonal penicillin, such as piperacillin-tazobactam with a dose range of 3.375 g or 4.5 g and frequency every 6, 8, or 12 hours based on provider discretion.

anti-pseudomonal penicillin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• Located in a participating emergency department or medical intensive care unit
• Less than 12 hours from presentation to study hospital
• Treating clinician initiating an order for an anti-pseudomonal cephalosporin or anti-pseudomonal penicillin

You may not qualify if:

• Known receipt of \> 1 dose of an anti-pseudomonal cephalosporin or anti-pseudomonal penicillin during the last 7 days
• Current documented allergy to cephalosporins or penicillin
• Known to be a prisoner
• Treating clinicians feel that either an anti-pseudomonal cephalosporin or anti-pseudomonal penicillin is required or contraindicated for the optimal treatment of the patient, including for more directed antibiotic therapy against known prior resistant infections or suspected sepsis with an associated central nervous system infection

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (26)

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• Balderia PG, Chandorkar A, Kim Y, Patnaik S, Sloan J, Newman GC. Dosing Cefepime for Renal Function Does Not Completely Prevent Neurotoxicity in a Patient With Kidney Transplant. J Patient Saf. 2018 Jun;14(2):e33-e34. doi: 10.1097/PTS.0000000000000225.

  PMID: 26102002 BACKGROUND

• Qian ET, Casey JD, Wright A, Wang L, Shotwell MS, Siemann JK, Dear ML, Stollings JL, Lloyd BD, Marvi TK, Seitz KP, Nelson GE, Wright PW, Siew ED, Dennis BM, Wrenn JO, Andereck JW, Han JH, Self WH, Semler MW, Rice TW; Vanderbilt Center for Learning Healthcare and the Pragmatic Critical Care Research Group. Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial. JAMA. 2023 Oct 24;330(16):1557-1567. doi: 10.1001/jama.2023.20583.

  PMID: 37837651 DERIVED

• Qian ET, Casey JD, Wright A, Wang L, Siemann J, Dear ML, Stollings J, Lloyd BD, Seitz K, Nelson G, Wright P, Siew ED, Dennis B, Wrenn J, Andereck J, Self WH, Semler MW, Rice TW; Vanderbilt Learning Healthcare System Platform Investigators. Protocol and statistical analysis plan for the Antibiotic Choice On ReNal outcomes (ACORN) randomised clinical trial. BMJ Open. 2023 Mar 10;13(3):e066995. doi: 10.1136/bmjopen-2022-066995.

  PMID: 36898748 DERIVED

MeSH Terms

Conditions

Sepsis; Neurotoxicity Syndromes

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Results Point of Contact

• Title: Edward T Qian, MD
• Organization: Vanderbilt University Medical Center

edward.t.qian@vumc.org

615-322-2386

Study Officials

• Edward T Qian, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Patients and providers will necessarily be unblinded, but outcomes will be analyzed by a blind assessor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Clinical Fellow

Model Details: This study will be performed as a pragmatic, randomized controlled clinical trial with parallel group assignment.

Study Record Dates

• First Submitted: October 22, 2021
• First Posted: October 26, 2021
• Study Start: November 10, 2021
• Primary Completion: October 21, 2022
• Study Completion: October 21, 2022
• Last Updated: December 22, 2023
• Results First Posted: December 22, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: The data will become available 3 months following publication of outcomes and will remain available for at least 5 years.
• Access Criteria: Data will be made available to researchers who provide a methodologically sound proposal that has been approved by the Vanderbilt Institutional Review Board and the study executive committee.

Locations

US (1)