Pragmatic Trial Of Alerts for Use of Mineralocorticoid Receptor Antagonists

Study Overview
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Brief Summary
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The primary objective of this study is to determine if a best practice alert (BPA) system that prompts providers to consider the addition of a mineralocorticoid receptor antagonist (MRA) in eligible patients with heart failure with reduced ejection fraction (HFrEF) will result in increased prescription of this guideline-recommended therapy. The system will also inform providers about FDA-approved potassium binders for the treatment of hyperkalemia if elevated potassium is a barrier for MRA use and will provide educational information on the evidence for MRA therapy in these patients.

Detailed Description
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Despite the robust literature demonstrating improved outcomes with the use of mineralocorticoid antagonists (MRAs) in patients with heart failure with reduced ejection fraction (HFrEF), MRAs continue to be underused in clinical practice. This underuse often stems from the perceived risks of hyperkalemia, including a prior history of hyperkalemia and acute or chronic kidney disease, as well as the cautioned use for those with potassium greater than 5.0 mEq/L, as recommended in national societal guidelines. New potassium binders have recently been approved by the United States Food and Drug Administration (FDA) to treat hyperkalemia. It remains unknown if a best practice alert built into the clinical electronic health record can facilitate MRA prescription in eligible patients by providing guideline-based information about MRA recommendations and evidence, as well as informing practitioners about available treatments for hyperkalemia. This is a pragmatic, cluster-randomized, open-label interventional trial to test the comparative effectiveness of an EHR BPA system that informs practitioners about MRAs for HFrEF and, if necessary, potassium-binders that are FDA-approved for hyperkalemia, versus usual care (no alert, current standard of care). One hundred and fifty outpatient Cardiology and Internal Medicine providers (to include physicians and advanced practice providers (nurse practitioners, physician assistants, and advanced practice registered nurses)) practicing at affiliated locations will be enrolled and undergo randomization to either the intervention (alert) group or a control (usual care) group. Those in the intervention group will receive an informational alert for their eligible adult outpatients (those with HFrEF not currently prescribed an MRA). Those in the control group will not receive any alerts and will continue to care for patients as usual. The primary outcome will be the proportion of patients with HFrEF who have an active prescription for an MRA at 6 months following randomization.

Official Title
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Pragmatic Trial Of Messaging to Providers About Treatment With Mineralocorticoid Receptor Antagonists

Conditions
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Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
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* Behavioral: Best Practice Alert


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults equal to or greater than 18 years of age Outpatients of providers randomized into the study within Internal Medicine and Cardiology outpatient clinics Diagnosis of heart failure with reduced ejection fraction (LVEF less than or equal to 40% on the most recent TTE) Registration in the Yale Heart Failure Registry (NCT04237701) Not currently prescribed an MRA Exclusion Criteria: Absolute contraindication to MRAs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention - Best Practice Alert<br>Providers randomized to the intervention arm will have a best practice alert appear for each of their eligible patients upon opening of the order entry screen in the patient's medical record which alerts to the presence of HFrEF and the fact that the patient is not currently prescribed an MRA. A link to an order set for MRAs (or to potassium binders should a patient be hyperkalemic) will provided, along with a link to current best practices surrounding the use of MRAs. | Behavioral: Best Practice Alert<br>* Providers randomized to the intervention arm will have a best practice alert appear for each of their eligible patients upon opening of the order entry screen in the patient's medical record. This alert informs the provider to the presence of HFrEF and absence of MRA prescription, notes the patient's current LVEF, and notes the most recent labs, including NT-ProBNP, potassium, and creatinine. Providers will also have access to a link to best available guideline recommended information regarding use of MRAs and a link to both an order set for prescribing an MRA and an alternate order set with option for potassium monitoring should hyperkalemia be a concern. If a patient is hyperkalemic (i.e. K ≥ 5 mEq/L), a link to an order set for prescribing a potassium binder will be provided instead. If a provider feels that the recommended therapy is not indicated for a particular patient, he/she can select an available reason from the list provided within the alert.<br>|
| No Intervention: Usual Care<br>Providers will not receive a best practice alert for eligible patients and will continue to care for patients as usual. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with an active prescription for an MRA | Proportion of patients with an active prescription for an MRA, defined as a prescription present in the electronic health record for any drug in the MRA class that is active (not expired) and has remaining doses left at 6 months after the date of randomization. | Measured at 6 months post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of MRA prescriptions | Number of any MRA prescription during study period. | Within one year post randomization | 
| Percentage of MRA prescriptions filled | Percentage of prescriptions filled of initial MRA prescriptions written during the study period. | Within 30 days of written prescription | 
| Time to first MRA prescription | Time (in days) to first MRA prescription | From enrollment to time of MRA prescription | 
| Percentage of patients with Hyperkalemia (K>5.0) | Percentage of patients experiencing hyperkalemia (K greater than or equal to 5.0 mEq/L) | Within one year post randomization | 
| Percentage of patients with Hyperkalemia (K>5.5) | Percentage of patients experiencing hyperkalemia (K greater than or equal to 5.5 mEq/L) | Within one year post randomization | 
| Percentage of patients with Hyperkalemia (K>5.0) with MRA | Percentage of patients experiencing hyperkalemia (K greater than or equal to 5.0 mEq/L) with an active MRA prescription | Within one year post randomization | 
| Percentage of patients with Hyperkalemia (K>5.5) with MRA | Percentage of patients experiencing hyperkalemia (K greater than or equal to 5.5 mEq/L) with an active MRA prescription | Within one year post randomization | 
| Percentage of patients with potassium binder prescription | Percentage of participants with active prescription for potassium binders | Measured at 1 month post randomization | 
| Percentage of patients with potassium binder prescription | Percentage of participants with active prescription for potassium binders | Measured at 2 months post randomization | 
| Percentage of patients with potassium binder prescription | Percentage of participants with active prescription for potassium binders | Measured at 3 months post randomization | 
| Percentage of patients with potassium binder prescription | Percentage of participants with active prescription for potassium binders | Measured at 4 months post randomization | 
| Percentage of patients with potassium binder prescription | Percentage of participants with active prescription for potassium binders | Measured at 5 months post randomization | 
| Percentage of patients with potassium binder prescription | Percentage of participants with active prescription for potassium binders | Measured at 6 months post randomization | 
| Percentage of patients with potassium binder + MRA prescription | Percentage of participants with active prescription for potassium binders and MRA | Measured at 1 month post randomization | 
| Percentage of patients with potassium binder + MRA prescription | Percentage of participants with active prescription for potassium binders and MRA | Measured at 2 months post randomization | 
| Percentage of patients with potassium binder + MRA prescription | Percentage of participants with active prescription for potassium binders and MRA | Measured at 3 months post randomization | 
| Percentage of patients with potassium binder + MRA prescription | Percentage of participants with active prescription for potassium binders and MRA | Measured at 4 months post randomization | 
| Percentage of patients with potassium binder + MRA prescription | Percentage of participants with active prescription for potassium binders and MRA | Measured at 5 months post randomization | 
| Percentage of patients with potassium binder + MRA prescription | Percentage of participants with active prescription for potassium binders and MRA | Measured at 6 months post randomization | 
| Type of potassium binder prescribed | Type of first potassium binder prescribed | First potassium binder prescribed at any point between enrollment and study completion | 
| Rationale for provider not prescribing an MRA if indicated (intervention group only) | Provider-documented (via the best practice alert) rationale for not prescribing indicated MRA (intervention group only) | Any rationale provided within one year post randomization | 
| Rationale for provider not prescribing a potassium binder if indicated (intervention group only) | Provider-documented (via the best practice alert) rationale for not prescribing indicated potassium binder (intervention group only) | Any rationale provided within one year post randomization | 
| Percentage of patients with ED visits | Percentage of patients with any ED visit | Measured at 1 month post randomization | 
| Percentage of patients with ED visits | Percentage of patients with any ED visit | Measured at 3 months post randomization | 
| Percentage of patients with ED visits | Percentage of patients with any ED visit | Measured at 6 months post randomization | 
| Percentage of patients with ED visits | Percentage of patients with any ED visit | Measured at 12 months post randomization | 
| ED visit count | Count of ED visits per patient | Measured at 1 month post randomization | 
| ED visit count | Count of ED visits per patient | Measured at 3 months post randomization | 
| ED visit count | Count of ED visits per patient | Measured at 6 months post randomization | 
| ED visit count | Count of ED visits per patient | Measured at 12 months post randomization | 
| Rates of Heart failure-related hospital admissions | Rates of HF-related hospital admissions (uses computations phenotype) | Measured at 1 month post randomization | 
| Rates of Heart failure-related hospital admissions | Rates of HF-related hospital admissions (uses computations phenotype) | Measured at 3 months post randomization | 
| Rates of Heart failure-related hospital admissions | Rates of HF-related hospital admissions (uses computations phenotype) | Measured at 6 months post randomization | 
| Rates of Heart failure-related hospital admissions | Rates of HF-related hospital admissions (uses computations phenotype) | Measured at 12 months post randomization | 
| Rates Outpatient visits | Rates of outpatient visits | Measured at 1 monnh post randomization | 
| Rate of Outpatient visits | Rates of outpatient visits | Measured at 3 months post randomization | 
| Rate of Outpatient visits | Rates of outpatient visits | Measured at 6 months post randomization | 
| Rate of Outpatient visits | Rates of outpatient visits | Measured at 12 months post randomization | 
| Rate of ED visit + IV diuretics | Rates of total ED visits in which a dose of IV diuretics was given | Measured at 1 month post randomization | 
| Rate of ED visit + IV diuretics | Rates of total ED visits in which a dose of IV diuretics was given | Measured at 3 months post randomization | 
| Rate of ED visit + IV diuretics | Rates of total ED visits in which a dose of IV diuretics was given | Measured at 6 months post randomization | 
| Rate of ED visit + IV diuretics | Rates of total ED visits in which a dose of IV diuretics was given | Measured at 12 months post randomization | 
| All-cause mortality | Rates of all-cause mortality | Measured at 1 month post randomization | 
| All-cause mortality | Rates of all-cause mortality | Measured at 3 months post randomization | 
| All-cause mortality | Rates of all-cause mortality | Measured at 6 months post randomization | 
| All-cause mortality | Rates of all-cause mortality | Measured at 12 months post randomization | 
| Total healthcare associated costs | Total healthcare-associated cost per patient | Measured at 1 month post randomization | 
| Total healthcare associated costs | Total healthcare-associated cost per patient | Measured at 3 months post randomization | 
| Total healthcare associated costs | Total healthcare-associated cost per patient | Measured at 6 months post randomization | 
| Total healthcare associated costs | Total healthcare-associated cost per patient | Measured at 12 months post randomization | 
| Rates of documented hyperkalemia at an ED visit | Documented hyperkalemia (K ≥ 5.5 mEq/L) at an ED visit | Within one year post randomization | 
| Rates of documented hyperkalemia at an outpatient visit | Documented hyperkalemia (K ≥ 5.5 mEq/L) at an outpatient visit | Within one year post randomization | 
| Rates of documented hyperkalemia during a hospital HF admission | Documented hyperkalemia (K ≥ 5.5 mEq/L) at an HF-related hospital admission | Within one year post randomization | 
| Frequency of outpatient potassium monitoring | Frequency of outpatient potassium monitoring | Within one year post randomization | 
| Frequency of outpatient potassium monitoring +/- MRA | Frequency of outpatient potassium monitoring for those with an active prescription of MRA vs. not | Within one year post randomization | 
| Frequency of outpatient potassium monitoring +/- potassium binder | Frequency of outpatient potassium monitoring for those with an active prescription of potassium binder vs. not | Within one year post randomization |