Trial Outcomes & Findings for Effect of Antibiotic Choice On ReNal Outcomes (ACORN) (NCT NCT05094154)

NCT ID: NCT05094154

Last Updated: 2023-12-22

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 2634 participants
• Primary outcome timeframe: 14 days post-enrollment
• Results posted on: 2023-12-22

Participant Flow

Among 3,806 patients who met inclusion criteria, 1,172 were excluded. Of the 2,634 enrolled and randomized, 4 were prisoners and excluded post-randomization from subsequent data collection and analysis, 119 did not receive a dose of anti-pseudomonal cephalosporin or anti-pseudomonal penicillin in the 7 days after enrollment and were not included in the primary analysis, leaving 2,511 included in the primary analysis. Thus 2,511 matches the number reported in the Study Design section.

Participant milestones

Measure	Anti-pseudomonal Cephalosporin Participants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin. anti-pseudomonal cephalosporin: 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 Penicillin Participants in the anti-pseudomonal penicillin arm will receive at least one dose of an anti-pseudomonal penicillin. anti-pseudomonal penicillin: 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.
Overall Study STARTED	1277	1357
Overall Study COMPLETED	1214	1297
Overall Study NOT COMPLETED	63	60

Reasons for withdrawal

Measure	Anti-pseudomonal Cephalosporin Participants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin. anti-pseudomonal cephalosporin: 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 Penicillin Participants in the anti-pseudomonal penicillin arm will receive at least one dose of an anti-pseudomonal penicillin. anti-pseudomonal penicillin: 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.
Overall Study Participants experiencing incarceration or involuntary detainment.	3	1
Overall Study Did not receive appropriate drug in 7 days post-enrollment.	60	59

Baseline Characteristics

One value was missing for a participant in the anti-pseudomonal penicillin group.

Baseline characteristics by cohort

Measure	Anti-pseudomonal Cephalosporin n=1214 Participants Participants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin. anti-pseudomonal cephalosporin: 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 Penicillin n=1297 Participants Participants in the anti-pseudomonal penicillin arm will receive at least one dose of an anti-pseudomonal penicillin. anti-pseudomonal penicillin: 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.	Total n=2511 Participants Total of all reporting groups
Age, Continuous	57 years n=1214 Participants • One value was missing for a participant in the anti-pseudomonal penicillin group.	59 years n=1296 Participants • One value was missing for a participant in the anti-pseudomonal penicillin group.	58 years n=2510 Participants • One value was missing for a participant in the anti-pseudomonal penicillin group.
Sex: Female, Male Female	523 Participants n=1214 Participants • One value was missing for a participant in the anti-pseudomonal penicillin group.	548 Participants n=1296 Participants • One value was missing for a participant in the anti-pseudomonal penicillin group.	1071 Participants n=2510 Participants • One value was missing for a participant in the anti-pseudomonal penicillin group.
Sex: Female, Male Male	691 Participants n=1214 Participants • One value was missing for a participant in the anti-pseudomonal penicillin group.	748 Participants n=1296 Participants • One value was missing for a participant in the anti-pseudomonal penicillin group.	1439 Participants n=2510 Participants • One value was missing for a participant in the anti-pseudomonal penicillin group.
Race/Ethnicity, Customized Race and Ethnicity · White, non-Hispanic	913 Participants n=1186 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.	950 Participants n=1264 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.	1863 Participants n=2450 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.
Race/Ethnicity, Customized Race and Ethnicity · Black, non-Hispanic	190 Participants n=1186 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.	209 Participants n=1264 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.	399 Participants n=2450 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.
Race/Ethnicity, Customized Race and Ethnicity · Hispanic	59 Participants n=1186 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.	73 Participants n=1264 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.	132 Participants n=2450 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.
Race/Ethnicity, Customized Race and Ethnicity · Other	24 Participants n=1186 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.	32 Participants n=1264 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.	56 Participants n=2450 Participants • 28 values were unknown for participants in the anti-pseudomonal cephalosporin group and 33 values were unknown for participants in anti-pseudomonal penicillin group.
Region of Enrollment United States	1214 participants n=1214 Participants	1297 participants n=1297 Participants	2511 participants n=2511 Participants

PRIMARY outcome

Timeframe: 14 days post-enrollment

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

Outcome measures

Measure	Anti-pseudomonal Cephalosporin n=1214 Participants Participants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin. anti-pseudomonal cephalosporin: 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 Penicillin n=1297 Participants Participants in the anti-pseudomonal penicillin arm will receive at least one dose of an anti-pseudomonal penicillin. anti-pseudomonal penicillin: 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.
Acute Kidney Injury (AKI) Ordinal Scale 0 = Survived without AKI	910 Participants	952 Participants
Acute Kidney Injury (AKI) Ordinal Scale 1 = Survived with Stage 1 AKI	86 Participants	100 Participants
Acute Kidney Injury (AKI) Ordinal Scale 2 = Survived with Stage 2 AKI	41 Participants	70 Participants
Acute Kidney Injury (AKI) Ordinal Scale 3 = Survived with Stage 3 AKI	85 Participants	97 Participants
Acute Kidney Injury (AKI) Ordinal Scale 4 = Died	92 Participants	78 Participants

SECONDARY outcome

Timeframe: 14 days post-enrollment

Composite outcome of death within 14 days, new renal replacement therapy within 14 days, or stage 2 or higher AKI at day 14

Outcome measures

Measure	Anti-pseudomonal Cephalosporin n=1214 Participants Participants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin. anti-pseudomonal cephalosporin: 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 Penicillin n=1297 Participants Participants in the anti-pseudomonal penicillin arm will receive at least one dose of an anti-pseudomonal penicillin. anti-pseudomonal penicillin: 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.
Major Adverse Kidney Events Within 14 Days (MAKE14)	124 Participants	114 Participants

SECONDARY outcome

Timeframe: 14 days post-enrollment

The number of days alive and free of coma and delirium in the 14 days after enrollment

Outcome measures

Measure	Anti-pseudomonal Cephalosporin n=1214 Participants Participants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin. anti-pseudomonal cephalosporin: 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 Penicillin n=1297 Participants Participants in the anti-pseudomonal penicillin arm will receive at least one dose of an anti-pseudomonal penicillin. anti-pseudomonal penicillin: 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.
Delirium and Coma-Free Days to Day 14	14 days Interval 14.0 to 14.0	14 days Interval 14.0 to 14.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 14 days post-enrollment

Patient disposition (ex. floor unit or intensive care unit) at day 14 post-enrollment from the emergency department.

Outcome measures

Measure	Anti-pseudomonal Cephalosporin n=1135 Participants Participants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin. anti-pseudomonal cephalosporin: 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 Penicillin n=1243 Participants Participants in the anti-pseudomonal penicillin arm will receive at least one dose of an anti-pseudomonal penicillin. anti-pseudomonal penicillin: 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.
Post-Emergency Department Disposition Home	26 participants	23 participants
Post-Emergency Department Disposition Ward	1016 participants	1117 participants
Post-Emergency Department Disposition ICU	93 participants	103 participants

Adverse Events

Anti-pseudomonal Cephalosporin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 104 deaths

Anti-pseudomonal Penicillin

Serious events: 0 serious events

Other events: 1 other events

Deaths: 106 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Anti-pseudomonal Cephalosporin n=1214 participants at risk Participants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin. anti-pseudomonal cephalosporin: 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 Penicillin n=1297 participants at risk Participants in the anti-pseudomonal penicillin arm will receive at least one dose of an anti-pseudomonal penicillin. anti-pseudomonal penicillin: 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.
Immune system disorders Blood product related allergy	0.00% 0/1214 • 28 days. Per the protocol and SAP, the primary, secondary, and exploratory outcomes were reported as clinical outcomes not as AEs unless the event was Definitely Related or Probably or Possibly Related to the study. ONLY the following types of AEs were collected, recorded, and reportable: * AEs that are Serious and Definitely Related, Probably or Possibly Related, or of Uncertain Relationship. * AEs that are Unexpected and Definitely Related, Probably or Possibly Related, or of Uncertain Relationship.	0.08% 1/1297 • Number of events 1 • 28 days. Per the protocol and SAP, the primary, secondary, and exploratory outcomes were reported as clinical outcomes not as AEs unless the event was Definitely Related or Probably or Possibly Related to the study. ONLY the following types of AEs were collected, recorded, and reportable: * AEs that are Serious and Definitely Related, Probably or Possibly Related, or of Uncertain Relationship. * AEs that are Unexpected and Definitely Related, Probably or Possibly Related, or of Uncertain Relationship.

Additional Information

Edward T Qian, MD

Vanderbilt University Medical Center

Phone: 615-322-2386

Email: edward.t.qian@vumc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place