Acute Kidney Injury
Conditions
Brief summary
This study will enroll hospitalized adults with acute kidney injury (AKI) and randomize them to usual care versus an electronic alert coupled to a best practices order set.
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. The investigators conducted a pilot, randomized trial of electronic alerts for acute kidney injury in 2014. The trial, which randomized 2400 patients with AKI as defined by an increase in creatinine of 0.3mg/dl over 48 hours or 50% over 7 days, found that alerting physicians to the presence of AKI did not improve the course of acute kidney injury, reduce dialysis or death rates. However this study was conducted in a single hospital, and the alert itself did not describe specific actions that a provider could take. In the present proposal, the investigators seek to expand upon their prior study to determine both the modes of alerting that would be most effective and to determine if targeting alerts (such as to patients on medications that may worsen acute kidney injury) will improve effectiveness. This study will be a randomized, controlled trial of an electronic AKI alert system. Using the Kidney Disease: Improve Global Outcomes creatinine criteria, inpatients at several hospitals will be randomized to usual care versus electronic alerting. The primary outcome will be a composite of progression of acute kidney injury, dialysis and death.
Interventions
OTHERAKI Alert
Provider's will receive a pop-up alert in the electronic health record until AKI is documented in the problem list or AKI resolves.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult ≥ 18 years admitted to a participating study hospital * Acute Kidney Injury as defined by KDIGO consensus creatinine criteria (0.3mg/dl increase in serum creatinine over 48 hours or 50% relative increase over 7 days).
Exclusion criteria
* ESKD diagnosis code * Dialysis order prior to AKI onset * Initial creatinine \>=4.0mg/dl * Prior admission in which patient was randomized. * Admission to hospice service or comfort measures only order * Kidney transplant within 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of Progression of AKI, Inpatient Dialysis, or Inpatient Death | 14 days from randomization | Progression of AKI is defined by an increase in KDIGO creatinine stage from that present at the time of randomization. Dialysis is defined by the receipt of hemodialysis, continuous renal replacement therapy or peritoneal dialysis. Isolated ultrafiltration treatments (for the purpose of volume removal) will not be included. Mortality will be determined from hospital administrative records. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dialysis | 14 days from randomization | 14-day, inpatient, or discharged on dialysis |
| AKI Progression | 14 days from randomization | Percent of patients who progress to stage 2 AKI and to stage 3 AKI |
| AKI Duration | 14 days from randomization | Number of participants with AKI duration of \<2 days, 2-\<days, and 7+ days (Aki duration defined as time in days between AKI onset and AKI cessation during index hospitalization) |
| Mortality | 14 days from randomization | 14-day or inpatient mortality |
| Index Hospitalization Cost | Index hospitalization through discharge, up to one year | Cost of index hospitalization, measured in direct and total costs. Direct costs reflect those associated with direct patient contact involving billable services (for example lab, nursing costs, and supplies). Total costs also include non-billable support services such as medical records, human resources, accounting, support staff, utilities and dietary costs. |
| Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | 24 hours from randomization to discharge, up to one year | Best practices assessed include: Avoidance of nephrotoxins (cessation of order or absence of de novo order of IV contrast agent, aminoglycoside, NSAID, or ACE inhibitor within 24 hours of randomization), fluid administration (administration of fluids within 24 hours of randomization), 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 occurring within 36 hours of randomization), documentation of urine output (within 24 hours of randomization), renal consult order during index hospitalization. Each metric above is binary. Outcome is reported as a composite best practice outcome representing the proportion of best practices achieved per subject. |
| Number of Subjects With Chart Documentation of AKI | Index hospitalization | Proportion of subjects with chart documentation of AKI by post-discharge ICD-10 codes and by chart adjudication |
| Readmission Rate | 30 days from randomization | 30 day readmission rate |
Countries
United States
Participant flow
Recruitment details
From 3/29/2018 to 12/14/2019, 6,030 individuals met enrollment criteria and were randomized across 6 hospitals of a single healthcare system.
Participants by arm
| Arm | Count |
|---|---|
| Usual Care No alert will be fired. | 2,971 |
| Electronic AKI Alert A pop-up alert will fire when a provider opens the electronic health record of a patient with AKI until such time as AKI is documented in the problem list, or AKI resolves.
AKI Alert: Provider's will receive a pop-up alert in the electronic health record until AKI is documented in the problem list or AKI resolves. | 3,059 |
| Total | 6,030 |
Baseline characteristics
| Characteristic | Total | Electronic AKI Alert | Usual Care |
|---|---|---|---|
| ACE inhibitor/ARB in prior 72 hours | 1296 Participants | 670 Participants | 626 Participants |
| Age, Continuous | 71.2 years | 71 years | 71.3 years |
| Anion Gap, meq/L | 12 meq/L | 12 meq/L | 12 meq/L |
| Bicarbonate, meq/L | 24 meq/L | 24 meq/L | 24 meq/L |
| Blood Urea Nitrogen, mg/dL | 28 mg/dL | 28 mg/dL | 28 mg/dL |
| Cardiothoracic surgery in prior 72 hours | 245 Participants | 135 Participants | 110 Participants |
| Chloride, meq/L | 102 meq/L | 102 meq/L | 102 meq/L |
| Chronic Kidney Disease | 2290 Participants | 1163 Participants | 1127 Participants |
| Congestive Heart Failure | 2658 Participants | 1351 Participants | 1307 Participants |
| Contrast in prior 72 hours | 1209 Participants | 623 Participants | 586 Participants |
| COPD | 2064 Participants | 1049 Participants | 1015 Participants |
| Creatinine, mg/dL | 1.5 mg/dL | 1.5 mg/dL | 1.5 mg/dL |
| Depression | 1342 Participants | 655 Participants | 687 Participants |
| Diabetes Mellitus | 2484 Participants | 1287 Participants | 1197 Participants |
| eGFR at admission (ml/min/1.73m2) | 55.4 ml/min/1.73m2 | 55.8 ml/min/1.73m2 | 55.1 ml/min/1.73m2 |
| ER Patient | 201 Participants | 93 Participants | 108 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 620 Participants | 331 Participants | 289 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5376 Participants | 2712 Participants | 2664 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 34 Participants | 16 Participants | 18 Participants |
| Hemoglobin, g/dL | 10.6 g/dL | 10.5 g/dL | 10.7 g/dL |
| Hospital 1 (Urban, teaching) | 2515 Participants | 1277 Participants | 1238 Participants |
| Hospital 2 (Urban, teaching) | 1248 Participants | 649 Participants | 599 Participants |
| Hospital 3 (Urban, teaching) | 935 Participants | 479 Participants | 456 Participants |
| Hospital 4 (Suburban, teaching) | 567 Participants | 275 Participants | 292 Participants |
| Hospital 5 (Suburban, non-teaching) | 554 Participants | 276 Participants | 278 Participants |
| Hospital 6 (Suburban, non-teaching) | 211 Participants | 103 Participants | 108 Participants |
| Hypertension | 4944 Participants | 2510 Participants | 2434 Participants |
| ICU Patient | 1923 Participants | 962 Participants | 961 Participants |
| Liver Disease | 855 Participants | 458 Participants | 397 Participants |
| Malignancy | 931 Participants | 460 Participants | 471 Participants |
| Medical Admission | 4564 Participants | 2284 Participants | 2280 Participants |
| Nadir creatinine in 48 hrs prior to randomization, mg/dL | 1.1 mg/dL | 1.1 mg/dL | 1.1 mg/dL |
| NSAID in prior 72 hours | 791 Participants | 388 Participants | 403 Participants |
| Platelet Count, (cells*1000/ul) | 201 cells*1000/ul | 200 cells*1000/ul | 202.5 cells*1000/ul |
| Potassium, meq/L | 4.2 meq/L | 4.2 meq/L | 4.2 meq/L |
| PPI in prior 72 hours | 1361 Participants | 677 Participants | 684 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 14 Participants | 8 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 75 Participants | 40 Participants | 35 Participants |
| Race (NIH/OMB) Black or African American | 946 Participants | 484 Participants | 462 Participants |
| Race (NIH/OMB) More than one race | NA Participants | NA Participants | NA Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 7 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 42 Participants | 23 Participants | 19 Participants |
| Race (NIH/OMB) White | 4442 Participants | 2234 Participants | 2208 Participants |
| Region of Enrollment United States | 6030 participants | 3059 participants | 2971 participants |
| Sex: Female, Male Female | 2882 Participants | 1442 Participants | 1440 Participants |
| Sex: Female, Male Male | 3148 Participants | 1617 Participants | 1531 Participants |
| Sodium, meq/L | 138 meq/L | 138 meq/L | 138 meq/L |
| Time from admission to randomization, hours | 50.3 hours | 50.1 hours | 50.7 hours |
| Time from AKI to randomization, hours | 0.5 hours | 0.5 hours | 0.5 hours |
| Unique providers reached | 7 Providers | 7 Providers | 7 Providers |
| Ward Patient | 3906 Participants | 2004 Participants | 1902 Participants |
| White Blood Cell Count, (cells*1000/ul) | 9.8 cells*1000/uL | 9.8 cells*1000/uL | 9.8 cells*1000/uL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 265 / 2,971 | 272 / 3,059 |
| other Total, other adverse events | 0 / 2,971 | 0 / 3,059 |
| serious Total, serious adverse events | 0 / 2,971 | 0 / 3,059 |
Outcome results
Primary
Composite of Progression of AKI, Inpatient Dialysis, or Inpatient Death
Progression of AKI is defined by an increase in KDIGO creatinine stage from that present at the time of randomization. Dialysis is defined by the receipt of hemodialysis, continuous renal replacement therapy or peritoneal dialysis. Isolated ultrafiltration treatments (for the purpose of volume removal) will not be included. Mortality will be determined from hospital administrative records.
Time frame: 14 days from randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Composite of Progression of AKI, Inpatient Dialysis, or Inpatient Death | 622 Participants |
| Electronic AKI Alert | Composite of Progression of AKI, Inpatient Dialysis, or Inpatient Death | 653 Participants |
Comparison: In our retrospective analysis of patients with AKI at 3 potential study hospitals, the composite outcome was 24.5%. A clinically meaningful relative reduction in this risk would be 20%. 5,024 patients (2,512 in each group) would have 90% power to detect a difference in outcome at least this extreme at a two-sided alpha of 0.05 as calculated using the Cochran-Mantel-Haenszel test. We have elected to increase this number by 20% to account for potential contamination.p-value: 0.6795% CI: [0.93, 1.13]Cochran-Mantel-Haenszel
Secondary
AKI Duration
Number of participants with AKI duration of \<2 days, 2-\<days, and 7+ days (Aki duration defined as time in days between AKI onset and AKI cessation during index hospitalization)
Time frame: 14 days from randomization
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | AKI Duration | <2 days | 2108 Participants |
| Usual Care | AKI Duration | 2-<7 days | 722 Participants |
| Usual Care | AKI Duration | 7+ days | 141 Participants |
| Electronic AKI Alert | AKI Duration | <2 days | 2239 Participants |
| Electronic AKI Alert | AKI Duration | 2-<7 days | 700 Participants |
| Electronic AKI Alert | AKI Duration | 7+ days | 120 Participants |
Secondary
AKI Progression
Percent of patients who progress to stage 2 AKI and to stage 3 AKI
Time frame: 14 days from randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | AKI Progression | 461 Participants |
| Electronic AKI Alert | AKI Progression | 487 Participants |
Secondary
Dialysis
14-day, inpatient, or discharged on dialysis
Time frame: 14 days from randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Dialysis | 93 Participants |
| Electronic AKI Alert | Dialysis | 106 Participants |
Secondary
Index Hospitalization Cost
Cost of index hospitalization, measured in direct and total costs. Direct costs reflect those associated with direct patient contact involving billable services (for example lab, nursing costs, and supplies). Total costs also include non-billable support services such as medical records, human resources, accounting, support staff, utilities and dietary costs.
Time frame: Index hospitalization through discharge, up to one year
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Usual Care | Index Hospitalization Cost | Direct Costs | 10300 dollars |
| Usual Care | Index Hospitalization Cost | Total Costs | 19100 dollars |
| Electronic AKI Alert | Index Hospitalization Cost | Total Costs | 20100 dollars |
| Electronic AKI Alert | Index Hospitalization Cost | Direct Costs | 10600 dollars |
Secondary
Mortality
14-day or inpatient mortality
Time frame: 14 days from randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Mortality | 265 Participants |
| Electronic AKI Alert | Mortality | 272 Participants |
Secondary
Number of Subjects With Chart Documentation of AKI
Proportion of subjects with chart documentation of AKI by post-discharge ICD-10 codes and by chart adjudication
Time frame: Index hospitalization
Population: Chart documentation via ICD-10 codes (code N17) have been collected. Documentation via chart adjudication has not yet been collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Number of Subjects With Chart Documentation of AKI | 1871 Participants |
| Electronic AKI Alert | Number of Subjects With Chart Documentation of AKI | 2141 Participants |
Secondary
Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization
Best practices assessed include: Avoidance of nephrotoxins (cessation of order or absence of de novo order of IV contrast agent, aminoglycoside, NSAID, or ACE inhibitor within 24 hours of randomization), fluid administration (administration of fluids within 24 hours of randomization), 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 occurring within 36 hours of randomization), documentation of urine output (within 24 hours of randomization), renal consult order during index hospitalization. Each metric above 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Urine Output Measurement | 2130 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Contrast exposure | 102 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | NSAID exposure | 166 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | IV fluid drip order | 1034 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | IV fluid bolus order | 339 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Urinalysis | 444 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Subsequent Creatinine Measurement (28 hours) | 2532 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Renal Consult (within 14 days) | 517 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Aminoglycoside exposure | 19 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Aminoglycoside exposure among those already receiving aminoglycoside | 8 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | NSAID exposure among those already receiving NSAIDs | 129 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | ACE/ARB exposure | 425 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | ACE/ARB exposure among those already receiving ACE/ARB | 326 Participants |
| Usual Care | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | AKI documentation (at end of encounter) | 1871 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Subsequent Creatinine Measurement (28 hours) | 2666 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Renal Consult (within 14 days) | 541 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | ACE/ARB exposure | 424 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Aminoglycoside exposure among those already receiving aminoglycoside | 5 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Contrast exposure | 115 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | AKI documentation (at end of encounter) | 2141 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | NSAID exposure among those already receiving NSAIDs | 103 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | IV fluid drip order | 1174 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Aminoglycoside exposure | 14 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | IV fluid bolus order | 397 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | ACE/ARB exposure among those already receiving ACE/ARB | 331 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Urinalysis | 519 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | Urine Output Measurement | 2242 Participants |
| Electronic AKI Alert | Proportion of AKI Best Practices Achieved Per Subject During Index Hospitalization | NSAID exposure | 144 Participants |
Secondary
Readmission Rate
30 day readmission rate
Time frame: 30 days from randomization
Population: Data have not yet been collected.