Acute Kidney InjuryNCT02771977
Drug-Targeted Alerts for Acute Kidney Injury
A study testing Drug-specific alert in people with Acute Kidney Injury, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury
- What is being tested?
- Drug-specific alert
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5,060 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2020to 4 Jan 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale New Haven Hospital
New Haven, Connecticut, 06510
About this study
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.
Read the 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
- Being tested
- Drug-specific alert
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug-specific alertOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Usual Care | No intervention | No alert will be fired. |
| Drug-specific alert | Experimental | A drug-specific AKI alert, including information about the drug of interest as well as the presence of AKI will be fired. Receives: Other: Drug-specific alert |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With Progression of AKI OR Dialysis OR Death
Progression of AKI is defined by an increase in KDIGO creatinine stage from time of randomization to the present. Dialysis is defined by the receipt of hemodialysis, continuous renal replacement therapy or peritoneal dialysis. Isolated ultrafiltration treatments will not be included. Mortality will be determined from hospital records.
Measured: 14 days from Randomization
Secondary outcomes (13)
Percentage of Patients for Whom Any One of the Targeted Medications is Discontinued
The Percentage of patients for whom the targeted agent was discontinued within 24 hours from randomization. For individuals with active orders for more than one targeted agent, cessation of any will be adequate to meet this endpoint.
Measured: Assessed within 24 hours from randomization
14- Day Mortality Rate
Percentage of patients who expire within 14 days of randomization
Measured: Assessed from date of randomization to date of death from any cause, within 14 days of randomization
Inpatient Mortality Rate
Percentage of patients who expire during index hospitalization.
Measured: Assessed from point of randomization to the date of death from any cause during the end of current index hospitalization, up to 365 days
Percentage of Patients Who Receive Dialysis Within 14 Days of Randomization
Receipt of hemodialysis, continuous renal replacement, or peritoneal dialysis within 14 days of randomization
Measured: Assessed from point of randomization to date of first documented dialysis order, within 14 days of randomization
Percentage of Patients on Inpatient Dialysis
Receipt of hemodialysis, continuous renal replacement, or peritoneal dialysis during index hospitalization
Measured: Assessed from point of randomization to the date of first documented dialysis order during index hospitalization, up to 365 days
Percentage of Patients Discharged on Dialysis
Active orders for dialysis at the point of discharge from the index hospitalization
Measured: Assessed at the point of discharge from index hospitalization, up to 365 days post randomization
Percentage of Patients With AKI Progression From Stage 1 to Stage 2
Progression to stage 2 AKI, represented by a doubling of baseline creatinine levels.
Measured: Assessed from date of randomization to date of documented AKI progression, within 14 days of randomization
Percentage of Patients With AKI Progression From Stage 2 to Stage 3
Progression to stage 3 AKI, represented by a tripling of baseline creatinine levels.
Measured: Assessed from date of randomization to date of documented AKI progression, within 14 days of randomization
AKI Duration
Time in hours between AKI onset and AKI cessation during index hospitalization
Measured: Assessed from the point of randomization to the point of AKI cessation during index hospitalization, up to 365 days
Readmission Rate
Number of readmissions within 30 days of discharge from index hospitalization
Measured: Within 30 days of index hospitalization discharge
Index Hospitalization Cost
Total cost of index hospitalization
Measured: Assessed from point of randomization to the date of discharge from index hospitalization, up to 365 days post randomization
Percentage 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 constrast 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.
Measured: Assessed from 24 hours from randomization up to discharge of index hospitalization
Percentage of Subjects With Chart Documentation of AKI
Percentage of subjects with chart documentation of AKI by post-discharge ICD-10 codes and by chart adjudication
Measured: Assessed from time of randomization through to date of index hospitalization discharge, up to 365 days post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2016 (estimated)
- Study start24 Aug 2020
- Primary completion20 Dec 2021
- Study completion4 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 5,060 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02771977
- Sponsor's protocol ID
- 2000025786
- Other IDs
- 1R01DK113191-01A1
- Status last verified
- Feb 2024
- First submitted
- 11 May 2016
- Last updated
- 15 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Wissel BD, Percy Z, Zachem TJ, Beaulieu-Jones B, Kohane IS, Goldstein SL, Gecili E, Dexheimer JW. Heterogenous effect of automated alerts on mortality. J Am Med Inform Assoc. 2026 Mar 1;33(3):653-662. doi: 10.1093/jamia/ocaf222.
PubMed 41445428Wissel 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.
PubMed 40832403Wilson 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.
PubMed 37198160
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Drug-Targeted Alerts for Acute Kidney Injury
- ClinicalTrials.gov ID
- NCT02771977
- Acronym / sponsor ID
- 2000025786
- Conditions
- Acute Kidney Injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,060 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 24 Aug 2020 (actual)
- Primary completion
- 20 Dec 2021 (actual)
- Study completion
- 4 Jan 2022 (actual)
- First posted
- 13 May 2016 (estimated)
- Results
- Posted 29 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Usual Care | No intervention | –No alert will be fired. |
| Drug-specific alert | Experimental | Other: Drug-specific alertA drug-specific AKI alert, including information about the drug of interest as well as the presence of AKI will be fired. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Drug-specific alertA drug-specific alert, informing the provider of the presence of AKI as well as recent exposure to a potentially nephrotoxic agent, will be fired. | Other | Drug-specific alert |
Primary outcome
Percentage of Patients With Progression of AKI OR Dialysis OR Death
Time frame: 14 days from Randomization
Progression of AKI is defined by an increase in KDIGO creatinine stage from time of randomization to the present. Dialysis is defined by the receipt of hemodialysis, continuous renal replacement therapy or peritoneal dialysis. Isolated ultrafiltration treatments will not be included. Mortality will be determined from hospital records.
13 secondary outcomes
Percentage of Patients for Whom Any One of the Targeted Medications is Discontinued
Time frame: Assessed within 24 hours from randomization
14- Day Mortality Rate
Time frame: Assessed from date of randomization to date of death from any cause, within 14 days of randomization
Inpatient Mortality Rate
Time frame: Assessed from point of randomization to the date of death from any cause during the end of current index hospitalization, up to 365 days
Percentage of Patients Who Receive Dialysis Within 14 Days of Randomization
Time frame: Assessed from point of randomization to date of first documented dialysis order, within 14 days of randomization
Percentage of Patients on Inpatient Dialysis
Time frame: Assessed from point of randomization to the date of first documented dialysis order during index hospitalization, up to 365 days
Percentage of Patients Discharged on Dialysis
Time frame: Assessed at the point of discharge from index hospitalization, up to 365 days post randomization
Percentage of Patients With AKI Progression From Stage 1 to Stage 2
Time frame: Assessed from date of randomization to date of documented AKI progression, within 14 days of randomization
Percentage of Patients With AKI Progression From Stage 2 to Stage 3
Time frame: Assessed from date of randomization to date of documented AKI progression, within 14 days of randomization
AKI Duration
Time frame: Assessed from the point of randomization to the point of AKI cessation during index hospitalization, up to 365 days
Readmission Rate
Time frame: Within 30 days of index hospitalization discharge
Index Hospitalization Cost
Time frame: Assessed from point of randomization to the date of discharge from index hospitalization, up to 365 days post randomization
Percentage of AKI "Best Practices" Achieved Per Subject During Index Hospitalization
Time frame: Assessed from 24 hours from randomization up to discharge of index hospitalization
Percentage of Subjects With Chart Documentation of AKI
Time frame: Assessed from time of randomization through to date of index hospitalization discharge, up to 365 days post randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41445428Wissel BD, Percy Z, Zachem TJ, Beaulieu-Jones B, Kohane IS, Goldstein SL, Gecili E, Dexheimer JW. Heterogenous effect of automated alerts on mortality. J Am Med Inform Assoc. 2026 Mar 1;33(3):653-662. doi: 10.1093/jamia/ocaf222.
- Derived from this study: PubMed 40832403Wissel 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.
- Derived from this study: PubMed 37198160Wilson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Drug-specific alert in people with Acute Kidney Injury, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With Progression of AKI OR Dialysis OR Death (time frame: 14 days from Randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02771977, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2024.