SepsisPhase 4ACORNNCT05094154
Effect of Antibiotic Choice On ReNal Outcomes (ACORN)
A Phase 4 study testing anti-pseudomonal cephalosporin and anti-pseudomonal penicillin in people with Sepsis and AKI, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, AKI, Neurotoxicity
- What is being tested?
- anti-pseudomonal cephalosporin and anti-pseudomonal penicillin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,634 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Nov 2021to 21 Oct 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
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.
Read the detailed description
Sepsis is a common condition associated with high mortality and morbidity. Antibiotics are an integral component of the management of patients with sepsis. Each hour delay in antibiotic administration in sepsis is associated with an increase in mortality. Clinical guidelines recommend early management bundles, including early broad-spectrum antibiotics, for patients with presumed sepsis in the emergency department and intensive care unit. Since the specific organism causing an infection is rarely known at clinical presentation, empiric broad-spectrum antibiotics are commonly prescribed. For patients at risk for resistant organisms, the most common regimens include vancomycin (to cover gram-positive organisms including methicillin-resistant Staphylococcus aureus) and an anti-pseudomonal cephalosporin or anti-pseudomonal penicillin (to cover gram-negative organisms including Pseudomonas).
Cephalosporins and penicillins are beta-lactam antibiotics that act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. They are commonly used for a variety of infections including empiric broad spectrum coverage for sepsis and suspected nosocomial infections. Several cephalosporins and penicillins have anti-pseudomonal activity, including cefepime, a fourth-generation cephalosporin, ceftazidime, a third-generation cephalosporin, and piperacillin-tazobactam, an extended-spectrum penicillin with beta-lactamase inhibitor. Anti-pseudomonal penicillins are the preferred agents for empiric broad spectrum coverage at many centers, and piperacillin-tazobactam, specifically, has the added benefit of treating anaerobic organisms.
Acute Kidney Injury (AKI) is a common complication of ICU admission. AKI is associated with a six to eight fold increase in mortality in ICU populations is therefore a common target of critical care trials. Sepsis is the most common cause of AKI and accounts for 40-50% of AKI in the intensive care unit (ICU). As the primary treatment for the underlying cause of sepsis, antibiotics are a critical treatment for acutely ill patients, but antibiotics may cause renal injury, and renally-cleared antibiotics may reach supratherapeutic levels in the setting of AKI. Vancomycin has long been associated with AKI. Recently, a number of retrospective observational analyses have examined a potential association between the concurrent administration of vancomycin and piperacillin-tazobactam and the development of AKI, compared with vancomycin alone. These data, however, are likely to be confounded by indication bias and studies evaluating whether piperacillin-tazobactam causes more AKI than other anti-pseudomonal antibiotics have been inconclusive.
Based on this preliminary, observational data, however, some institutions have elected to change their preferred broad spectrum antibiotic regimens from one including an anti-pseudomonal penicillin to one including an anti-pseudomonal cephalosporin. However, others have argued against this approach given the lack of randomized trials comparing the relative efficacy and safety of the two agents as well as observational data suggesting that cephalosporins may be associated with neuro-toxicity.
Tens of thousands of patients each year receive either anti-pseudomonal cephalosporins and penicillins, but no randomized trials have ever compared their relative effectiveness or safety. Each class of medications has been hypothesized to have toxicities that may be relevant for acutely ill patients. Because the relationship between antibiotic choice (anti-pseudomonal cephalosporins or anti-pseudomonal penicillins) and clinically relevant outcomes, such as AKI, are unknown, clinical trial data is urgently needed. Rigorous high-quality evidence that anti-pseudomonal cephalosporins, compared to anti-pseudomonal penicillins, decreases, increases or has no impact on the risk of AKI would have the potential to change the care received by thousands of acutely ill adults each year.
- Conditions
- Sepsis, AKI, Neurotoxicity
- Being tested
- anti-pseudomonal cephalosporin, anti-pseudomonal penicillin
- Medical subject headings
- Sepsis, Neurotoxicity Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-pseudomonal cephalosporinDrug
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 penicillinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| anti-pseudomonal cephalosporin | Active comparator | Participants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin. Receives: 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. Receives: Drug: anti-pseudomonal penicillin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
- = Stage 1 AKI (Creatinine increase by 1.5-1.9 times baseline OR increase by >= 0.3 mg/dL)
- = Stage 2 AKI (Creatinine increase by 2.0-2.9 times baseline)
- = Stage 3 AKI (Creatinine increase by >= 3.0 times baseline OR increase to >= 4.0 mg/dL OR New RRT)
- = Death
Measured: 14 days post-enrollment
Secondary outcomes (2)
Major Adverse Kidney Events Within 14 Days (MAKE14)
Composite outcome of death within 14 days, new renal replacement therapy within 14 days, or stage 2 or higher AKI at day 14
Measured: 14 days post-enrollment
Delirium and Coma-Free Days to Day 14
The number of days alive and free of coma and delirium in the 14 days after enrollment
Measured: 14 days post-enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2021
- Study start10 Nov 2021
- Primary completion21 Oct 2022
- Study completion21 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study will be performed as a pragmatic, randomized controlled clinical trial with parallel group assignment.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2,634 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, EDDIE QIAN, Vanderbilt University Medical Center
- Investigators
- Edward T Qian, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05094154
- Sponsor's protocol ID
- 210591
- Acronym
- ACORN
- Status last verified
- Dec 2023
- First submitted
- 22 Oct 2021
- Last updated
- 22 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported will be made available (including data dictionaries) after de-identification.
Publications
Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet. 2018 Jul 7;392(10141):75-87. doi: 10.1016/S0140-6736(18)30696-2. Epub 2018 Jun 21.
PubMed 29937192Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
PubMed 28101605Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, Escobar GJ. The Timing of Early Antibiotics and Hospital Mortality in Sepsis. Am J Respir Crit Care Med. 2017 Oct 1;196(7):856-863. doi: 10.1164/rccm.201609-1848OC.
PubMed 28345952Damiani E, Donati A, Serafini G, Rinaldi L, Adrario E, Pelaia P, Busani S, Girardis M. Effect of performance improvement programs on compliance with sepsis bundles and mortality: a systematic review and meta-analysis of observational studies. PLoS One. 2015 May 6;10(5):e0125827. doi: 10.1371/journal.pone.0125827. eCollection 2015.
PubMed 25946168Thakar CV, Christianson A, Freyberg R, Almenoff P, Render ML. Incidence and outcomes of acute kidney injury in intensive care units: a Veterans Administration study. Crit Care Med. 2009 Sep;37(9):2552-8. doi: 10.1097/CCM.0b013e3181a5906f.
PubMed 19602973Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005 Aug 17;294(7):813-8. doi: 10.1001/jama.294.7.813.
PubMed 16106006Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Aug;41(8):1411-23. doi: 10.1007/s00134-015-3934-7. Epub 2015 Jul 11.
PubMed 26162677Gomez H, Kellum JA. Sepsis-induced acute kidney injury. Curr Opin Crit Care. 2016 Dec;22(6):546-553. doi: 10.1097/MCC.0000000000000356.
PubMed 27661757Arnaud FCS, Liborio AB. Attributable nephrotoxicity of vancomycin in critically ill patients: a marginal structural model study. J Antimicrob Chemother. 2020 Apr 1;75(4):1031-1037. doi: 10.1093/jac/dkz520.
PubMed 31904834Filippone EJ, Kraft WK, Farber JL. The Nephrotoxicity of Vancomycin. Clin Pharmacol Ther. 2017 Sep;102(3):459-469. doi: 10.1002/cpt.726. Epub 2017 Jun 5.
PubMed 28474732Bellos I, Karageorgiou V, Pergialiotis V, Perrea DN. Acute kidney injury following the concurrent administration of antipseudomonal beta-lactams and vancomycin: a network meta-analysis. Clin Microbiol Infect. 2020 Jun;26(6):696-705. doi: 10.1016/j.cmi.2020.03.019. Epub 2020 Mar 25.
PubMed 32222460Rutter WC, Burgess DR, Talbert JC, Burgess DS. Acute kidney injury in patients treated with vancomycin and piperacillin-tazobactam: A retrospective cohort analysis. J Hosp Med. 2017 Feb;12(2):77-82. doi: 10.12788/jhm.2684.
PubMed 28182801Carreno J, Smiraglia T, Hunter C, Tobin E, Lomaestro B. Comparative incidence and excess risk of acute kidney injury in hospitalised patients receiving vancomycin and piperacillin/tazobactam in combination or as monotherapy. Int J Antimicrob Agents. 2018 Nov;52(5):643-650. doi: 10.1016/j.ijantimicag.2018.08.001. Epub 2018 Aug 10.
PubMed 30103003Downes KJ, Cowden C, Laskin BL, Huang YS, Gong W, Bryan M, Fisher BT, Goldstein SL, Zaoutis TE. Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children. JAMA Pediatr. 2017 Dec 4;171(12):e173219. doi: 10.1001/jamapediatrics.2017.3219. Epub 2017 Dec 4.
PubMed 28973124Kalligeros M, Karageorgos SA, Shehadeh F, Zacharioudakis IM, Mylonakis E. The association of acute kidney injury with the concomitant use of vancomycin and piperacillin/tazobactam in children: A systematic review and meta-analysis. Antimicrob Agents Chemother. 2019 Sep 9;63(12):e01572-19. doi: 10.1128/AAC.01572-19. Epub 2019 Oct 7.
PubMed 31591125
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Antibiotic Choice On ReNal Outcomes (ACORN)
- ClinicalTrials.gov ID
- NCT05094154
- Acronym / sponsor ID
- ACORN / 210591
- Conditions
- Sepsis, AKI, Neurotoxicity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,634 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 10 Nov 2021 (actual)
- Primary completion
- 21 Oct 2022 (actual)
- Study completion
- 21 Oct 2022 (actual)
- First posted
- 26 Oct 2021 (actual)
- Results
- Posted 22 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Sepsis is a common condition associated with high mortality and morbidity. Antibiotics are an integral component of the management of patients with sepsis. Each hour delay in antibiotic administration in sepsis is associated with an increase in mortality. Clinical guidelines recommend early management bundles, including early broad-spectrum antibiotics, for patients with presumed sepsis in the emergency department and intensive care unit. Since the specific organism causing an infection is rarely known at clinical presentation, empiric broad-spectrum antibiotics are commonly prescribed. For patients at risk for resistant organisms, the most common regimens include vancomycin (to cover gram-positive organisms including methicillin-resistant Staphylococcus aureus) and an anti-pseudomonal cephalosporin or anti-pseudomonal penicillin (to cover gram-negative organisms including Pseudomonas).
Cephalosporins and penicillins are beta-lactam antibiotics that act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. They are commonly used for a variety of infections including empiric broad spectrum coverage for sepsis and suspected nosocomial infections. Several cephalosporins and penicillins have anti-pseudomonal activity, including cefepime, a fourth-generation cephalosporin, ceftazidime, a third-generation cephalosporin, and piperacillin-tazobactam, an extended-spectrum penicillin with beta-lactamase inhibitor. Anti-pseudomonal penicillins are the preferred agents for empiric broad spectrum coverage at many centers, and piperacillin-tazobactam, specifically, has the added benefit of treating anaerobic organisms.
Acute Kidney Injury (AKI) is a common complication of ICU admission. AKI is associated with a six to eight fold increase in mortality in ICU populations is therefore a common target of critical care trials. Sepsis is the most common cause of AKI and accounts for 40-50% of AKI in the intensive care unit (ICU). As the primary treatment for the underlying cause of sepsis, antibiotics are a critical treatment for acutely ill patients, but antibiotics may cause renal injury, and renally-cleared antibiotics may reach supratherapeutic levels in the setting of AKI. Vancomycin has long been associated with AKI. Recently, a number of retrospective observational analyses have examined a potential association between the concurrent administration of vancomycin and piperacillin-tazobactam and the development of AKI, compared with vancomycin alone. These data, however, are likely to be confounded by indication bias and studies evaluating whether piperacillin-tazobactam causes more AKI than other anti-pseudomonal antibiotics have been inconclusive.
Based on this preliminary, observational data, however, some institutions have elected to change their preferred broad spectrum antibiotic regimens from one including an anti-pseudomonal penicillin to one including an anti-pseudomonal cephalosporin. However, others have argued against this approach given the lack of randomized trials comparing the relative efficacy and safety of the two agents as well as observational data suggesting that cephalosporins may be associated with neuro-toxicity.
Tens of thousands of patients each year receive either anti-pseudomonal cephalosporins and penicillins, but no randomized trials have ever compared their relative effectiveness or safety. Each class of medications has been hypothesized to have toxicities that may be relevant for acutely ill patients. Because the relationship between antibiotic choice (anti-pseudomonal cephalosporins or anti-pseudomonal penicillins) and clinically relevant outcomes, such as AKI, are unknown, clinical trial data is urgently needed. Rigorous high-quality evidence that anti-pseudomonal cephalosporins, compared to anti-pseudomonal penicillins, decreases, increases or has no impact on the risk of AKI would have the potential to change the care received by thousands of acutely ill adults each year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- This study will be performed as a pragmatic, randomized controlled clinical trial with parallel group assignment.
| Arm | Type | Receives |
|---|---|---|
| anti-pseudomonal cephalosporin | Active comparator | Drug: anti-pseudomonal cephalosporinParticipants in the anti-pseudomonal cephalosporin arm will receive at least one dose of an anti-pseudomonal cephalosporin. |
| anti-pseudomonal penicillin | Active comparator | Drug: anti-pseudomonal penicillinParticipants in the anti-pseudomonal penicillin arm will receive at least one dose of an anti-pseudomonal penicillin. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-pseudomonal cephalosporinProviders 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. | Drug | anti-pseudomonal cephalosporin |
| anti-pseudomonal penicillinProviders 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. | Drug | anti-pseudomonal penicillin |
Primary outcome
Acute Kidney Injury (AKI) Ordinal Scale
Time frame: 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
2 secondary outcomes
Major Adverse Kidney Events Within 14 Days (MAKE14)
Time frame: 14 days post-enrollment
Delirium and Coma-Free Days to Day 14
Time frame: 14 days post-enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29937192Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet. 2018 Jul 7;392(10141):75-87. doi: 10.1016/S0140-6736(18)30696-2. Epub 2018 Jun 21.
- Background: PubMed 28101605Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
- Background: PubMed 28345952Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, Escobar GJ. The Timing of Early Antibiotics and Hospital Mortality in Sepsis. Am J Respir Crit Care Med. 2017 Oct 1;196(7):856-863. doi: 10.1164/rccm.201609-1848OC.
- Background: PubMed 25946168Damiani E, Donati A, Serafini G, Rinaldi L, Adrario E, Pelaia P, Busani S, Girardis M. Effect of performance improvement programs on compliance with sepsis bundles and mortality: a systematic review and meta-analysis of observational studies. PLoS One. 2015 May 6;10(5):e0125827. doi: 10.1371/journal.pone.0125827. eCollection 2015.
- Background: PubMed 19602973Thakar CV, Christianson A, Freyberg R, Almenoff P, Render ML. Incidence and outcomes of acute kidney injury in intensive care units: a Veterans Administration study. Crit Care Med. 2009 Sep;37(9):2552-8. doi: 10.1097/CCM.0b013e3181a5906f.
- Background: PubMed 16106006Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005 Aug 17;294(7):813-8. doi: 10.1001/jama.294.7.813.
- Background: PubMed 26162677Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Aug;41(8):1411-23. doi: 10.1007/s00134-015-3934-7. Epub 2015 Jul 11.
- Background: PubMed 27661757Gomez H, Kellum JA. Sepsis-induced acute kidney injury. Curr Opin Crit Care. 2016 Dec;22(6):546-553. doi: 10.1097/MCC.0000000000000356.
- Background: PubMed 31904834Arnaud FCS, Liborio AB. Attributable nephrotoxicity of vancomycin in critically ill patients: a marginal structural model study. J Antimicrob Chemother. 2020 Apr 1;75(4):1031-1037. doi: 10.1093/jac/dkz520.
- Background: PubMed 28474732Filippone EJ, Kraft WK, Farber JL. The Nephrotoxicity of Vancomycin. Clin Pharmacol Ther. 2017 Sep;102(3):459-469. doi: 10.1002/cpt.726. Epub 2017 Jun 5.
- Background: PubMed 32222460Bellos I, Karageorgiou V, Pergialiotis V, Perrea DN. Acute kidney injury following the concurrent administration of antipseudomonal beta-lactams and vancomycin: a network meta-analysis. Clin Microbiol Infect. 2020 Jun;26(6):696-705. doi: 10.1016/j.cmi.2020.03.019. Epub 2020 Mar 25.
- Background: PubMed 28182801Rutter WC, Burgess DR, Talbert JC, Burgess DS. Acute kidney injury in patients treated with vancomycin and piperacillin-tazobactam: A retrospective cohort analysis. J Hosp Med. 2017 Feb;12(2):77-82. doi: 10.12788/jhm.2684.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported will be made available (including data dictionaries) after de-identification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward T Qian, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing anti-pseudomonal cephalosporin and anti-pseudomonal penicillin in people with Sepsis and AKI, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute Kidney Injury (AKI) Ordinal Scale (time frame: 14 days post-enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05094154, which also lists 26 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2023.