Pragmatic Trial Of Alerts for Use of Mineralocorticoid Receptor Antagonists (PROMPT-MRA)

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Behavioral: Best Practice Alert

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1210
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Cardiology/Internal Medicine Outpatient Clinics of Yale New Health System

Participation Criteria

Eligibility Criteria

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

Description

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

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: Intervention - Best Practice Alert; 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; 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.
No Intervention: Usual Care; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subgroup Analysis: Hyperkalemia at randomization	Hyperkalemia at randomization at both thresholds of ≥ 5.0 mEq/L and K ≥ 5.5 mEq/L	At randomization
Subgroup Analysis: Prior hyperkalemia (IDC-10 Code)	Prior documentation of hyperkalemia by ICD-10 Code during the past 1 year	From one year prior to randomization up to randomization
Subgroup Analysis: Prior hyperkalemia (K history)	Prior documentation of hyperkalemia by history of K 5.0 mEq/L during the past 1 year	From one year prior to randomization up to randomization
Subgroup Analysis: Patient demographics	The following demographics subgroups will be captured: Age <65 years of age, sex, race	At randomization
Subgroup Analysis: Chronic Kidney Disease	Chronic kidney disease (CKD) stage ≥ stage III, glomerular filtration rate (GFR) <60	At randomization
Subgroup Analysis: Insurance status	Insurance status (commercial, public (Medicare, Medicaid), other, none)	At randomization
Subgroup Analysis: GDMT medications	Number of concomitant active prescriptions for GDMT medications (beta blocker, ACEi/ARB/ARNI, SGLT2-inhibitor)	At randomization
Subgroup Analysis: Provider type	The following provider characteristics will be captured: title (advanced practitioner, resident physician, fellow physician, attending physician), history of or current Cardiology fellowship training, years of training post-graduate medical school	At randomization

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Vifor Pharma; Relypsa, Inc.
• Investigators: Principal Investigator: Francis P Wilson, MD MSCE, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2021
• Primary Completion (Actual): August 6, 2023
• Study Completion (Actual): February 6, 2024

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: May 21, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 22, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 2000030513

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data underlying results for publication will be shared upon publication.
• IPD Sharing Time Frame: Upon publication; indefinitely.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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