Drug-Targeted Alerts for Acute Kidney Injury

NCT ID: NCT02771977

Last Updated: 2024-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 5060 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-24
• Study Completion Date: 2022-01-04

Brief Summary

In this trial, patients with acute kidney injury who have recently received a drug that may affect kidney function will be randomized to having an alert placed in the electronic health record or usual care.

Detailed Description

Acute kidney injury (AKI) carries a significant, independent risk of mortality among hospitalized patients. Recent studies have demonstrated increased mortality among patients with even small increases in serum creatinine concentration. International guidelines for the treatment of AKI focus on appropriate management of drug dosing, avoiding nephrotoxic exposures, and careful attention to fluid and electrolyte balance. Early nephrologist involvement may also improve outcomes in AKI. Without appropriate provider recognition of AKI, however, none of these measures can be taken, and patient outcomes may suffer. AKI is frequently overlooked by clinicians, but carries a substantial cost, morbidity and mortality burden.

Our research group recently conducted a large-scale multicenter randomized controlled trial of electronic alerts for AKI throughout the Yale New Haven Health System from 2018 to 2020. The trial, which enrolled 6,030 patients with AKI, randomized patients between usual care and an intervention group whereby providers received a general AKI alert informing them to the presence of AKI and the patient's recent creatinine trends, and provided a link to an AKI-specific order set. Our study showed that, overall, alerting physicians to the presence of AKI did not demonstrate a difference in the rate of our primary outcome of progression of AKI, dialysis, or death, nor were there any differences in process measures accessed (i.e. provider actions) between the two groups, however, there was substantial heterogeneity among the study sites. Given the highly heterogenous nature of AKI, a more personalized approach may be warranted. Further, this study enrolled all patients who developed AKI rather than a targeted subset of patients who may benefit, such as those AKI patients receiving potentially harmful kidney-toxic medications. In the present proposal, we seek to expand upon our prior study to determine if the use of medication targeted electronic alerts will modify provider behavior, particularly in regards to nephrotoxic medication use and cessation, in the care of hospitalized patients with AKI and/or reduce the rates of progression to AKI, dialysis, or mortality in hospitalized patients.

The current study is a randomized, controlled trial of a medication-targeted electronic AKI alert system. Using the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria, inpatients at 4 different teaching hospitals of the Yale New Haven Health System that have had at least one dose of a nephrotoxic agent of interest within 24 hours of AKI onset will be randomized to either usual care or a medication-targeted alert that informs the provider of the presence of AKI and the patient's recent exposures to the targeted classes of medications with an option to discontinue. The primary outcome will be a composite of AKI progression, dialysis, or mortality within 14 days of randomization. Secondary outcomes will focus on the rate of cessation of any medication of interest within 24 hours of randomization and various other best practice metrics.

Conditions

Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Usual Care

No alert will be fired.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Drug-specific alert

A drug-specific AKI alert, including information about the drug of interest as well as the presence of AKI will be fired.

Group Type: EXPERIMENTAL

Drug-specific alert

Intervention Type: OTHER

A drug-specific alert, informing the provider of the presence of AKI as well as recent exposure to a potentially nephrotoxic agent, will be fired.

Interventions

Drug-specific alert

A drug-specific alert, informing the provider of the presence of AKI as well as recent exposure to a potentially nephrotoxic agent, will be fired.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Acute Kidney Injury based upon the Kidney Disease: Improving Global Outcomes creatinine criteria (a 0.3mg/dl increase over 48 hours or 50% increase over 7 days) and an active order within the past 24 hours to one of the following classes of medications:
• Non-steroidal anti-inflammatory drug
• Renin Angiotensin Aldosterone System Antagonists
• Proton Pump Inhibitors

Exclusion Criteria

• Dialysis order prior to AKI onset
• Previous randomization
• Admission to a hospice service or CMO
• First hospital creatinine >=4.0 mg/dl
• ESKD diagnosis code
• Kidney transplant within six months prior to randomization

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Yale New Haven Hospital

New Haven, Connecticut, United States

Countries

United States

References

Wissel BD, Percy Z, Zachem TJ, Beaulieu-Jones B, Kohane IS, Goldstein SL, Gecili E, Dexheimer JW. Heterogeneous Effect of Automated Alerts on Mortality. medRxiv [Preprint]. 2025 Aug 13:2025.08.11.25333302. doi: 10.1101/2025.08.11.25333302.

Reference Type: DERIVED

PMID: 40832403 (View on PubMed)

Wilson FP, Yamamoto Y, Martin M, Coronel-Moreno C, Li F, Cheng C, Aklilu A, Ghazi L, Greenberg JH, Latham S, Melchinger H, Mansour SG, Moledina DG, Parikh CR, Partridge C, Testani JM, Ugwuowo U. A randomized clinical trial assessing the effect of automated medication-targeted alerts on acute kidney injury outcomes. Nat Commun. 2023 May 17;14(1):2826. doi: 10.1038/s41467-023-38532-3.

Reference Type: DERIVED

PMID: 37198160 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01DK113191-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000025786

Identifier Type: -

Identifier Source: org_study_id