750 Participants Needed

Antibiotic Combinations for Acute Kidney Injury Risk

(MONACO Trial)

TM
Overseen ByTodd Miano, PharmD, PhD
Age: 18+
Sex: Any
Trial Phase: Phase 4
Sponsor: University of Pennsylvania
Must be taking: Vancomycin, Piperacillin-tazobactam, Cefepime
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two common antibiotic combinations to determine which one is less likely to cause acute kidney injury (AKI), a condition where kidneys suddenly stop functioning properly. The antibiotics involved are vancomycin paired with either piperacillin-tazobactam or cefepime, both used to treat infections in hospitalized patients. The study seeks more accurate indicators of kidney issues than the usual tests, aiming to identify which combination is safer for the kidneys. Individuals with a suspected or confirmed infection, for which either antibiotic combination is considered suitable, might be a good fit for this trial. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and this research helps understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it focuses on patients already prescribed certain antibiotics, so you may need to discuss your current medications with the trial team.

What is the safety track record for these treatments?

Research has shown that different combinations of antibiotics can affect the risk of sudden kidney problems, known as acute kidney injury (AKI). Studies have found no significant increase in kidney issues when vancomycin is used with cefepime compared to other antibiotic combinations. One study even found no difference in kidney health or worsening of AKI with this combination.

However, research consistently indicates that using vancomycin with piperacillin-tazobactam is linked to a higher risk of AKI. This combination is associated with more kidney problems, including more severe stages of AKI, compared to when vancomycin is used with other antibiotics like cefepime.

These findings suggest that while both combinations treat infections, the vancomycin-cefepime combination might be safer for kidney health than the vancomycin-piperacillin-tazobactam combination.12345

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these antibiotic combinations because they could offer a safer approach to treating infections in patients at risk for acute kidney injury. Traditional treatments often involve using single antibiotics, but combining Vancomycin with Cefepime or Piperacillin-Tazobactam might reduce the potential for kidney damage. These combinations are designed to maintain effectiveness against bacterial infections while minimizing the risk of harming the kidneys, a significant concern with current options. By exploring these combinations, researchers hope to find a treatment strategy that balances powerful infection-fighting capabilities with improved kidney safety.

What evidence suggests that this trial's treatments could be effective for reducing the risk of acute kidney injury?

This trial will compare the effectiveness and risk of kidney problems between two antibiotic combinations: vancomycin with cefepime and vancomycin with piperacillin-tazobactam. Studies have shown that both combinations effectively treat infections. However, research indicates a higher risk of kidney issues with vancomycin and piperacillin-tazobactam compared to vancomycin and cefepime. One study found that 17.5% of patients taking vancomycin with piperacillin-tazobactam developed kidney problems, while only 3.3% of those taking vancomycin with cefepime did. Another study reported similar kidney problem rates for both combinations, but vancomycin with cefepime still showed a slight advantage. Overall, while both treatments work well against infections, vancomycin with cefepime may pose a lower risk for kidney issues.16789

Are You a Good Fit for This Trial?

This trial is for hospitalized patients with suspected or confirmed infections where the doctor thinks both vancomycin combined with either piperacillin-tazobactam or cefepime are good treatment options, and expects to treat them for at least 48 hours.

Inclusion Criteria

My doctor plans to treat me with antibiotics for at least 48 hours.
My doctor approves using vancomycin with either piperacillin-tazobactam or cefepime.
I am 18 years old or older.
See 1 more

Exclusion Criteria

Previous enrollment in this study
Expected survival <24 hours and/or presence of do not resuscitate orders
History of antibiotic-resistant organisms (microbiological culture results showing bacterial isolates with resistant or intermediate susceptibility to any study drug within the prior 90 days)
See 8 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either Vancomycin with Cefepime or Vancomycin with Piperacillin-Tazobactam

5 days
Daily monitoring for 5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days
Follow-up assessments at 7, 14, 30, and 60 days

What Are the Treatments Tested in This Trial?

Interventions

  • Cefepime
  • Piperacillin-tazobactam
  • Vancomycin

Trial Overview

The study compares the risk of acute kidney injury when treating with two antibiotic combinations: vancomycin plus piperacillin-tazobactam versus vancomycin plus cefepime. It uses sensitive markers to detect kidney damage earlier than standard tests.

How Is the Trial Designed?

2

Treatment groups

Active Control

Group I: Vancomycin with CefepimeActive Control2 Interventions
Group II: Vancomycin with Piperacillin-TazobactamActive Control2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials
2,118
Recruited
45,270,000+

Citations

Progression of kidney injury with the combination of ... - PMC

Our study observed no difference in kidney-specific or other secondary outcomes, including the maximum serum creatinine in the first week and AKI progression, ...

Retrospective Cohort Study of the Incidence of Acute Kidney ...

Previous studies demonstrated that the combination of vancomycin and piperacillin-tazobactam increases the risk of AKI compared to vancomycin ...

Acute Kidney Injury with Vancomycin, Antipseudomonal ...

There were 120 patients in both VPT and VC groups. In the VPT group, 17.5% of patients (21/120) developed AKI, compared to 3.3% of patients (4/ ...

Renal Comparison of acute kidney injury risk associated ...

Overall, 333 patients were evaluated. The AKI rate in the vancomycin/PTZ group and vancomycin/FEP group were similar (19.5% vs. 17.3%, respectively, p = .

Study Details | NCT06954129 | A Pragmatic Clinical Trial ...

Although these regimens have similar effectiveness, recent observational evidence suggests they may differ in terms of the risk for acute kidney injury (AKI).

Acute kidney injury following the concurrent administration ...

The combination of vancomycin and piperacillin–tazobactam is associated with higher acute kidney injury rates than its parallel use with meropenem or cefepime.

Incidence of Acute Kidney Injury in Critically Ill Patients ...

Recent evidence suggests an increased risk of acute kidney injury (AKI) in patients who received a combination of vancomycin and piperacillin-tazobactam (VPT).

Risk of Acute Kidney Injury in Patients on Concomitant ...

Recent evidence suggests that among patients receiving vancomycin, receipt of concomitant piperacillin–tazobactam increases the risk of nephrotoxicity.

Comparative incidence of acute kidney injury in patients on ...

Abstract. Recent studies have shown that the incidence of nephrotoxicity increases when vancomycin is combined with a beta-lactam antibiotic.