Learning Alerts for Acute Kidney Injury

Uplift Modeling to More Narrowly Target Alerts for Acute Kidney Injury

The primary objective of this study is to determine whether the use of uplift (also known as Conditional Average Treatment Effect - CATE) modeling to empirically identify patients expected to benefit the most from AKI alerting and to target AKI alerts to these patients will reduce the rates of AKI progression, dialysis, and mortality.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Other: Alert

Detailed Description

Acute kidney injury (AKI) carries a significant, independent risk of mortality among hospitalized patients, but despite its association with poor clinical outcomes, AKI is asymptomatic and frequently overlooked by clinicians, with fewer than half of all AKI patients with documentation of the syndrome in the electronic medical record, which was associated with decreased rates of AKI clinical best practices.

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 (ELAIA-1). 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, despite the alert leading to some process of care changes such as measurement of creatinine and urinalysis. There was, however, substantial heterogeneity among the study sites. The proliferation of alerting systems that are ineffective can lead to the phenomenon of alert fatigue, whereby providers tend to ignore alerts in a high-alert environment, and can have deleterious effects on patient care. Further, given the highly heterogenous nature of AKI, a more personalized approach to AKI alerting may be warranted.

Uplift modeling, commonly used in marketing, is a novel concept in the medical field and aims to determine phenotypic characteristics that predict a response (benefit or harm) to a given intervention. In this way, patients who are predicted to benefit most from an intervention are identified and preferentially targeted. Uplift modeling of alerting systems has the potential to both improve alert effectiveness through intelligent targeting, and reduce alert fatigue.

In this study, we will expand upon our prior AKI alert trial to determine prospectively whether the use of uplift modeling to preferentially target patients expected to benefit from an AKI alert will reduce the rates of AKI progression, dialysis and death among hospitalized patients with AKI. Inpatients at 4 teaching hospitals within the YNHH system with AKI, based on the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria, will be randomized to a "recommended" group (with higher scores receiving alerts and lower scores not receiving alerts as recommended) versus an "anti-recommended" group (with higher scores not receiving alerts and lower scores receiving alerts as anti-recommended). The primary outcome will be a composite of AKI progression, dialysis, or mortality within 14 days of randomization. Secondary outcomes will focus on AKI-specific process measures.

• Study Type: Interventional
• Enrollment (Estimated): 3900
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Francis P Wilson, MD MSCE; Phone Number: 2037371704; Email: francis.p.wilson@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale New Haven Hospital
      • Contact: Francis P Wilson, MD MSCE; Email: francis.p.wilson@yale.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults ≥ 18 years
2. Admitted to a participating hospital

3. Has AKI as defined by creatinine criteria:

   • 0.3 mg/dl increase in inpatient serum creatinine over 48 hours OR
   • 50% relative increase in inpatient serum creatinine over 7 days

Exclusion Criteria:

1. Dialysis order prior to AKI onset
2. Initial creatinine ≥ 4.0 mg/dl
3. Prior admission in which patient was randomized
4. Admission to hospice service or comfort measures only order
5. ESKD diagnosis code
6. Kidney transplant within six months
7. Opted out of electronic health record research

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Recommended; Those whose uplift score represents a probability of benefit greater than 0.5 will generate an alert, while those whose uplift score represents a probability of benefit less than 0.5 will not generate an alert.	Other: Alert; An alert informing the provider of the presence of acute kidney injury will be fired.
Experimental: Anti-recommended; Those whose uplift score represents a probability of benefit greater than 0.5 will not generate an alert, while those whose uplift score represents a probability of benefit less than 0.5 will generate an alert.	Other: Alert; An alert informing the provider of the presence of acute kidney injury will be fired.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with progression to a higher stage of AKI OR Dialysis OR Death	Progression of AKI is defined as the increase in KDIGO stage from the time of randomization to the present. For patients who are discharged, we will impute 14-day creatinine using the last observation carried forward method. Dialysis is defined as the receipt of hemodialysis, continuous renal replacement therapy, or peritoneal dialysis. Isolated ultrafiltration treatments will not be included. Mortality will be determined from hospital administrative records.	Within 14 days from randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
14-day Mortality	Proportion of patients who expire from any cause	Assessed from point of randomization to date of death within 14 days of randomization
Inpatient mortality	Proportion of patients who expire from any cause	Assessed from point of randomization to date of death from any cause, up to one year post-randomization
14-day dialysis	Proportion of patients who receive dialysis (hemodialysis, continuous renal replacement therapy, or peritoneal dialysis)	Assessed from point of randomization to date of first documented dialysis order, within 14 days of randomization
Inpatient dialysis	Proportion of patients who receive dialysis (hemodialysis, continuous renal replacement therapy, or peritoneal dialysis)	Assess from point of randomization to date of first documented dialysis order during index hospitalization, up to one year post-randomization
Discharge on dialysis	Assessed as active orders for dialysis at point of discharge from index hospitalization	Assessed at point of discharge from index hospitalization, up to one year post-randomization
Progression to stage 2 AKI	Proportion of patients with a doubling of serum creatinine from the date of randomization to 14 days post randomization	Assessed from the date of randomization to 14 days post randomization
Progression to stage 3 AKI	Proportion of patients with a tripling of serum creatinine from the date of randomization to 14 days post randomization	Assessed from the date of randomization to 14 days post randomization
Duration of AKI	Defined as the time in hours between AKI onset and AKI cessation during index hospitalization	Assessed from the date of randomization to the cessation of AKI during index hospitalization, up to one year
30 day readmission rate	Proportion of patients with readmission within 30 days of index hospitalization discharge	Assessed from discharge date of index hospitalization to 30 days post discharge date
Index hospitalization cost	Total cost of index hospitalization	Assessed from point of randomization to date of discharge from index hospitalization, up to one year
Chart documentation of AKI	Proportion of patients with chart documentation of AKI as assessed by post-discharge ICD-10 codes	Assessed from date of randomization to date of discharge from index hospitalization, up to one year
Proportion of AKI "Best Practices" Achieved Per Subject During Index Hospitalization	Contrast administration (de novo order of IV contrast agent within 24 hours of randomization), fluid administration (within 24 hours of randomization), aminoglycoside administration (de novo order within 24 hours of randomization), NSAID administration/cessation (de novo order or cessation of order/absence of de novo order of NSAID within 24 hours of randomization), ACE inhibitor administration/cessation, urinalysis order (with or without microscopy within 24 hours of randomization), documentation of AKI (by ICD-9 and ICD-10 codes during index hospitalization), monitoring of creatinine (at least one serum creatinine measurement within 36 hours of randomization), documentation of urine output (within 24 hours of randomization), renal consult order during index hospitalization. Each metric is binary. Outcome is reported as a composite best practice outcome representing the proportion of best practices achieved per subject.	24 hours from randomization to discharge, up to one year post randomization

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Francis P Wilson, MD MSCE, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: May 13, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimated): May 30, 2016

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: YALEAKIALERTLEARN; 1R01DK113191-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No