Multi-hospital Electronic Decision Support for Drug-associated Acute Kidney Injury

Not Applicable

• Conditions: Acute Kidney Injury
• Interventions: Other: Level A; Other: Passive Alert; Other: Level B

• Registration Number: NCT06264752
• Lead Sponsor: University of Pittsburgh

Brief Summary

This study is a randomized controlled trial at eight hospitals within the University of Pittsburgh Medical Center-UPMC system. The project will assess the efficacy of a clinical surveillance system augmented with near real-time predictive analytics to support a pharmacist-led intervention delivered to attending physicians (primary service) to reduce the progression and complications of drug-associated acute kidney injury (D-AKI) in hospitalized (non-ICU) adults.

Detailed Description

Researchers will randomize 38 hospital service clusters to receive either: 1) a Cerner electronic medical record (EMR)-based AKI passive alert which is standard of care at UPMC: this alert provides decision support within the EMR for the diagnosis and basic staging of AKI but without specific recommendations for management (Usual Care Arm); or 2) protocolized stage-based intervention delivered to the physician by a pharmacist for consideration and approval. The intervention uses an automated alerting system to identify patients: 1) receiving a high-risk drug or drug combination associated with D-AKI and at low-risk for progression to either stage 2 AKI or stage 3 AKI per KDIGO criteria (Level A) and 2) patients without AKI or stage 1 AKI receiving a high-risk drug or drug combination associated with D-AKI and at high risk for progression to either stage 2 AKI or stage 3 AKI per KDIGO criteria, and patients with AKI stage 2 or stage 3 receiving a high-risk drug or drug combination associated with D-AKI or a medication that requires renal dose adjustment (Level B). This patient specific risk-profile will be coupled with recommendations for medication management and delivered to the physician by a pharmacist for consideration and approval. Additionally, the investigators will assess cost-effectiveness and physicians' perception of the pharmacist-led service.

The primary outcome is Major Adverse Kidney Events within 30 days of randomization (MAKE30), defined as defined as a composite of death, new kidney replacement therapy, or final serum creatinine ≥150% of reference at the earliest of hospital discharge or 30 days from study enrollment, whichever occurs first. Key secondary outcomes include: progression of AKI from time of Level B intervention (first alert generated) to hospital discharge, AKI intensity (duration of AKI by all stages, duration of AKI stage 2, and duration of AKI stage 3), and nephrotoxic burden.

Study Timeline

• Study First Submitted: 2024-02-08
• Study Start: 2024-02-15
• Study First Submitted QC: 2024-02-15
• Study First Posted: 2024-02-20
• Status Verified: 2024-07
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-04
• Primary Completion: 2026-01
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 625

Inclusion Criteria

Physician-subject Inclusion

• Physicians employed at UPMC hospital systems
• Attending physicians of record who care for patients across multiple units outside ICU/ED
• Physician cares for 1 or more patient receiving a system alert identifying high-risk for AKI

Patient-subject Inclusion

• System alert identifying risk for AKI
• Patient has attending physician who is participating in the randomized clusters
• After initial patient inclusion, an individual patient will not be eligible for re-inclusion until after 90 days. Re-inclusion will only be allowed if a separate hospital admission/encounter occurs and only starting on day 91

Exclusion Criteria

Physician-subject Exclusion

• Physicians of record who only care for ICU or ED patients
• Physicians who primarily provide care for transplant (heart, kidney, liver, etc.) patients
• Physicians who primarily provide consult services only (dermatology, rehabilitation, etc.)

Patient-subject Exclusion

• Patients with end stage renal disease on admission, baseline eGFR <15, comfort measures only, or died before the intervention could be delivered

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Protocolized stage-based intervention	Level A	The intervention uses an automated alerting system to identify patients: 1) receiving a high-risk drug or drug combination associated with AKI and at low-risk for progression to either stage 2 AKI or stage 3 AKI (Level A) and 2) patients without AKI or stage 1 AKI receiving a high-risk drug or drug combination associated with AKI and at high risk for progression to either stage 2 AKI or stage 3 AKI, and patients with AKI stage 2 or stage 3 receiving a high-risk drug or drug combination associated with AKI or a medication that requires renal dose adjustment (Level B). This patient specific risk-profile will be coupled with recommendations for medication management and delivered to the physician by a pharmacist for consideration and approval.
Protocolized stage-based intervention	Level B	The intervention uses an automated alerting system to identify patients: 1) receiving a high-risk drug or drug combination associated with AKI and at low-risk for progression to either stage 2 AKI or stage 3 AKI (Level A) and 2) patients without AKI or stage 1 AKI receiving a high-risk drug or drug combination associated with AKI and at high risk for progression to either stage 2 AKI or stage 3 AKI, and patients with AKI stage 2 or stage 3 receiving a high-risk drug or drug combination associated with AKI or a medication that requires renal dose adjustment (Level B). This patient specific risk-profile will be coupled with recommendations for medication management and delivered to the physician by a pharmacist for consideration and approval.
Usual Care	Passive Alert	A Cerner EMR-based AKI passive alert which is standard of care at UPMC.

Primary Outcome Measures

Name	Time	Method
Major Adverse Kidney Events within 30 days of randomization (MAKE30)	up to 30 days	Composite of death, new kidney replacement therapy, or final serum creatinine greater than or equal to 150 percent of reference at the earliest of hospital discharge or 30 days from study enrollment, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Progression of AKI from time of Level B intervention (first alert generated) to hospital discharge	up to 30 days	Percentage of high-risk patients without AKI at the time of a first level B alert who subsequently progress to maximum AKI severity stages 1, 2, or 3 before hospital discharge or 30 days, whichever comes first.; Percentage of high-risk patients diagnosed with stage-1 AKI at the time of a level B alert who subsequently progress to maximum severity stages 2 or 3 AKI before hospital discharge or 30 days, whichever comes first.; Percentage of high-risk patients diagnosed with stage-2 AKI at the time of a level B alert who subsequently progress to maximum severity stage 3 AKI before hospital discharge or 30 days, whichever comes first.
Nephrotoxic burden	up to 30 days	Drug.days\* in both study arms for those drugs considered possible/probable, probable and definitely related to AKI in adult, non-ICU patients.; \*Drug.days calculation: each drug and each day of therapy increases the burden by 1 drug.day.
AKI Intensity: Duration of AKI for all stages; Duration of AKI Stage 2; Duration of AKI stage 3	up to 30 days	AKI intensity rate (per 100 exposed patient-days) calculated as: number of days patients have AKI/ total number of AKI exposed patient-days standardized per 100 exposed days

Trial Locations

Locations (8)

UPMC Altoona; 🇺🇸 Altoona, Pennsylvania, United States

UPMC Horizon; 🇺🇸 Farrell, Pennsylvania, United States

UPMC McKeesport; 🇺🇸 McKeesport, Pennsylvania, United States

UPMC Jameson; 🇺🇸 New Castle, Pennsylvania, United States

UPMC Magee; 🇺🇸 PIttsburgh, Pennsylvania, United States

UPMC Presbyterian/Montefiore; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Shadyside; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Williamsport; 🇺🇸 Williamsport, Pennsylvania, United States