Acute Kidney Injury
Conditions
Brief summary
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.
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.
Interventions
OTHERAlert
An alert informing the provider of the presence of acute kidney injury will be fired.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Progression to a Higher Stage of AKI OR Dialysis OR Death | Within 14 days from randomization | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inpatient Mortality | Assessed from point of randomization to date of death from any cause, up to one year post-randomization | Proportion of patients who expire from any cause |
| 14-day Dialysis | Assessed from point of randomization to date of first documented dialysis order, within 14 days of randomization | Proportion of patients who receive dialysis (hemodialysis, continuous renal replacement therapy, or peritoneal dialysis) |
| Inpatient Dialysis | Assess from point of randomization to date of first documented dialysis order during index hospitalization, up to one year post-randomization | Proportion of patients who receive dialysis (hemodialysis, continuous renal replacement therapy, or peritoneal dialysis) |
| Discharge on Dialysis | Assessed at point of discharge from index hospitalization, up to one year post-randomization | Assessed as active orders for dialysis at point of discharge from index hospitalization |
| Progression to Stage 2 AKI | Assessed from the date of randomization to 14 days post randomization | Progression to Stage 2 AKI is defined as a doubling of serum creatinine between randomization and 14 days post randomization, and is considered a worsening of AKI. |
| 14-day Mortality | Assessed from point of randomization to date of death within 14 days of randomization | Proportion of patients who expire from any cause |
| Duration of AKI | Assessed from the date of randomization to the cessation of AKI during index hospitalization, up to one year | Defined as the time in hours between AKI onset and AKI cessation during index hospitalization |
| 30 Day Readmission Rate | Assessed from discharge date of index hospitalization to 30 days post discharge date | Proportion of patients with readmission within 30 days of index hospitalization discharge |
| Index Hospitalization Cost | Assessed from point of randomization to date of discharge from index hospitalization, up to one year | Total cost of index hospitalization |
| Chart Documentation of AKI | Assessed from date of randomization to date of discharge from index hospitalization, up to one year | Proportion of patients with chart documentation of AKI as assessed by post-discharge ICD-10 codes |
| Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | 24 hours from randomization to discharge, up to one year post randomization | 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. |
| Progression to Stage 3 AKI | Assessed from the date of randomization to 14 days post randomization | Progression to Stage 3 AKI is defined as a tripling of serum creatinine between the date of randomization and 14 days post randomization, and is considered a worsening of AKI. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred at 4 hospital sites across the Yale New Haven Hospital System. Identification of eligible patient subjects was performed within the Epic electronic medical record system based on inclusion and exclusion criteria by an algorithm embedded into the best practice alert. Randomization occurred the moment the best practice build identified a patient as being eligible.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Alert: An alert informing the provider of the presence of acute kidney injury will be fired. | 1,002 |
| 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.
Alert: An alert informing the provider of the presence of acute kidney injury will be fired. | 1,044 |
| Total | 2,046 |
Baseline characteristics
| Characteristic | Recommended | Anti-recommended | Total |
|---|---|---|---|
| Age, Continuous | 64.5 Years | 63.2 Years | 63.7 Years |
| Creatinine mg/dL | 1.5 mg/dL | 1.5 mg/dL | 1.5 mg/dL |
| Diastolic blood pressure (mmHg) | 67 mmHg | 68 mmHg | 68 mmHg |
| Peripheral Capillary Oxygen Saturation (SpO2, %) | 97 percent oxygen saturation | 97 percent oxygen saturation | 97 percent oxygen saturation |
| Pulse (bpm) | 80 beats per minute | 80 beats per minute | 80 beats per minute |
| Race/Ethnicity, Customized Black | 188 Participants | 206 Participants | 394 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 108 Participants | 140 Participants | 248 Participants |
| Sex/Gender, Customized Female | 537 Participants | 503 Participants | 1040 Participants |
| Systolic blood pressure (mmHg) | 118 mmHg | 118 mmHg | 118 mmHg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 169 / 1,002 | 185 / 1,044 |
| other Total, other adverse events | 0 / 1,002 | 0 / 1,044 |
| serious Total, serious adverse events | 0 / 1,002 | 0 / 1,044 |
Outcome results
Primary
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.
Time frame: Within 14 days from randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recommended | Proportion of Patients With Progression to a Higher Stage of AKI OR Dialysis OR Death | 190 Participants |
| Anti-recommended | Proportion of Patients With Progression to a Higher Stage of AKI OR Dialysis OR Death | 193 Participants |
Secondary
14-day Dialysis
Proportion of patients who receive dialysis (hemodialysis, continuous renal replacement therapy, or peritoneal dialysis)
Time frame: Assessed from point of randomization to date of first documented dialysis order, within 14 days of randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recommended | 14-day Dialysis | 38 Participants |
| Anti-recommended | 14-day Dialysis | 37 Participants |
Secondary
14-day Mortality
Proportion of patients who expire from any cause
Time frame: Assessed from point of randomization to date of death within 14 days of randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recommended | 14-day Mortality | 72 Participants |
| Anti-recommended | 14-day Mortality | 58 Participants |
Secondary
30 Day Readmission Rate
Proportion of patients with readmission within 30 days of index hospitalization discharge
Time frame: Assessed from discharge date of index hospitalization to 30 days post discharge date
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recommended | 30 Day Readmission Rate | 123 Participants |
| Anti-recommended | 30 Day Readmission Rate | 187 Participants |
Secondary
Chart Documentation of AKI
Proportion of patients with chart documentation of AKI as assessed by post-discharge ICD-10 codes
Time frame: Assessed from date of randomization to date of discharge from index hospitalization, up to one year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recommended | Chart Documentation of AKI | 442 Participants |
| Anti-recommended | Chart Documentation of AKI | 505 Participants |
Secondary
Discharge on Dialysis
Assessed as active orders for dialysis at point of discharge from index hospitalization
Time frame: Assessed at point of discharge from index hospitalization, up to one year post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recommended | Discharge on Dialysis | 28 Participants |
| Anti-recommended | Discharge on Dialysis | 22 Participants |
Secondary
Duration of AKI
Defined as the time in hours between AKI onset and AKI cessation during index hospitalization
Time frame: Assessed from the date of randomization to the cessation of AKI during index hospitalization, up to one year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recommended | Duration of AKI | 26.9 Hours |
| Anti-recommended | Duration of AKI | 27.7 Hours |
Secondary
Index Hospitalization Cost
Total cost of index hospitalization
Time frame: Assessed from point of randomization to date of discharge from index hospitalization, up to one year
Population: The data for this outcome were not collected and will not be accessed in the future. During outcome assessment, PIs were unable to get access to financial data to assess this outcome due to lack of institutional approval, therefore, no participants were analyzed. As this is the only financial-based outcome of the trial, this is the only outcome affected by this circumstance.
Secondary
Inpatient Dialysis
Proportion of patients who receive dialysis (hemodialysis, continuous renal replacement therapy, or peritoneal dialysis)
Time frame: Assess from point of randomization to date of first documented dialysis order during index hospitalization, up to one year post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recommended | Inpatient Dialysis | 39 Participants |
| Anti-recommended | Inpatient Dialysis | 41 Participants |
Secondary
Inpatient Mortality
Proportion of patients who expire from any cause
Time frame: Assessed from point of randomization to date of death from any cause, up to one year post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recommended | Inpatient Mortality | 169 Participants |
| Anti-recommended | Inpatient Mortality | 185 Participants |
Secondary
Progression to Stage 2 AKI
Progression to Stage 2 AKI is defined as a doubling of serum creatinine between randomization and 14 days post randomization, and is considered a worsening of AKI.
Time frame: Assessed from the date of randomization to 14 days post randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recommended | Progression to Stage 2 AKI | 91 Participants |
| Anti-recommended | Progression to Stage 2 AKI | 103 Participants |
Secondary
Progression to Stage 3 AKI
Progression to Stage 3 AKI is defined as a tripling of serum creatinine between the date of randomization and 14 days post randomization, and is considered a worsening of AKI.
Time frame: Assessed from the date of randomization to 14 days post randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recommended | Progression to Stage 3 AKI | 72 Participants |
| Anti-recommended | Progression to Stage 3 AKI | 66 Participants |
Secondary
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.
Time frame: 24 hours from randomization to discharge, up to one year post randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recommended | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | .6 Proportion achieved per subject |
| Anti-recommended | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | .6 Proportion achieved per subject |