Hyperkalaemia and Its Impact on Therapy With RAASi (REVIEW)

BuRden of Hyperkalaemia and EValuatIon of changEs to Therapy With Renin-angiotensin-aldosterone System Inhibitors Following Episodes of Elevated Potassium

Renin-angiotensin-aldosterone system inhibitors (RAASi) have transformed prognosis of patients with heart failure with reduced ejection fraction, diabetic nephropathy and chronic kidney disease. However, in everyday clinical practice patients often receive suboptimal doses of RAASi. The development of hyperkalaemia is one of the reasons for dose reduction or complete withdrawal of RAASi and this in turn is likely to have an adverse impact on patient outcomes. Yet it remains unknown precisely how often hyperkalaemia leads to changes to RAASi doses, if it is the sole reason, or whether this occurs in combination with other clinical situations such as worsened renal function and hypotension. It is also unclear what influences the decision-making process of healthcare professionals in managing patients with hyperkalaemia who take RAASi and if this is influenced by specialty, experience or indications for RAASi.

In order to improve our understanding of the problem we are taking forward a research study (made up of 3 complimentary studies). These data are needed to help achieve our ultimate goal of improving the care of patients with prognostic indication for RAASi.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction; Left Ventricular Systolic Dysfunction; Hyperkalaemia

Detailed Description

The study aims to answer the following research questions:

1. What is the incidence of hyperkalaemia following RAASi therapy initiation and uptitration in patients with a new diagnosis of HFrEF including those with a new diagnosis of post myocardial infarction (MI) left ventricular systolic dysfunction?
2. How does it impact on RAASi prescription?
3. How does hyperkalaemia impact on RAASi therapy according to the clinical indication for the drug(s) in an adult population of patients who are hospitalised or attending the emergency department (and not receiving dialysis) with hyperkalaemia and receiving RAASi?
4. At what level of hyperkalaemia do healthcare professionals consider making changes to RAASi and does it vary according to the clinical indication for the drug(s)?

• Study Type: Observational
• Enrollment (Anticipated): 900

Contacts and Locations

• Study Contact: Name: Sarah M Birkhoelzer, Dr; Phone Number: +44 02392 286000; Email: sarah.birkhoelzer@gmail.com
• Study Contact Backup: Name: Elena Cowan, Dr; Phone Number: 6750 +44 02392 286000; Email: elena.cowan@porthosp.nhs.uk

Study Locations

• United Kingdom
  • Portsmouth, United Kingdom
    • Recruiting
    • Portsmouth Hospitals University NHS Trust
    • Contact: Elena Cowan, Dr; Email: elena.cowan@porthosp.nhs.uk
    • Principal Investigator: Paul Kalra, Dr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Newly diagnosed heart failure with reduced ejection fraction (within 4 weeks of diagnosis, including those with post myocardial infarction left-ventricular systolic dysfunction)

Patients in ED or inpatients who already receive RAASi and who have at least 1 blood test with a potassium level of ≥5.5 mmol/l and not receiving dialysis prior to the episode of hyperkalaemia.

Healthcare professionals managing patients with hyperkalaemia and/or heart failure

Description

For patients with heart failure

Inclusion criteria

1. Patients with newly diagnosed HFrEF (within 4 weeks of diagnosis, including those with post MI LVSD, identified as outpatients or during hospital admission, typically for decompensated heart failure or post myocardial infarction) who are initiated on RAASi or have a clinical indication for uptitration of current RAASi (in patients already receiving RAASi for other indications).
2. Able to provide informed consent.
3. Age 18 and above.

Exclusion criteria: 1. Patients receiving dialysis.

For patients with hyperkalaemia

Inclusion criteria

1. Patients in ED or inpatients who already receive RAASi and who have at least 1 blood test with a potassium level of ≥5.5 mmol/l.
2. Able to provide informed consent.
3. Age 18 and above.

Exclusion criteria: 1. Patients receiving dialysis.

For healthcare professionals:

Inclusion criteria

1. Doctors, pharmacists, non-medical prescribers working at primary and secondary care.
2. Able to provide informed consent.
3. Age 18 and above.

Exclusion criteria: 1. None

As this is an observational study, patients in other research studies or receiving any specific treatments for hyperkalaemia (other than chronic dialysis) will not be excluded. After consent, patients will also be permitted to participate in other research studies should they so wish. Patients with covid-19 can also be included.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Patients with new diagnosis of heart failure with reduced ejection fraction; Patients with new diagnosis of heart failure with reduced ejection fraction who will be started on renin-angiotensin-aldosterone system inhibitors or in whom there is a plan to increase renin-angiotensin-aldosterone system inhibitors (if already taking prior to diagnosis of heart failure).
Patients with hyperkalaemia; Hospitalised patients and patients attending emergency department who have at least 1 blood test with a potassium level of ≥5.5 mmol/l.
Healthcare professionals managing patients with hyperkalaemia; Healthcare professionals (doctors, pharmacists, non-medical prescribers) who manage patients with hyperkalaemia and/or heart failure and hyperkalaemia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hyperkalaemia in patients with new diagnosis of HFrEF	Incidence of hyperkalaemia in patients with new heart failure with reduced ejection fraction started on renin-angiotensin-aldosterone receptor inhibitor(s)	12 months
Frequency of dose reduction/withdrawal for RAASi after hyperkalaemia in patients with HFrEF	Proportion of patients with new HFrEF started on RAASi who experienced RAASi dose reduction/withdrawal/prevention of dose uptitration due to hyperkalaemia.	12 months
Proportion of patients with hyperkalaemia (hospitalised or attending ED) who experienced changes to RAASi after episodes of hyperkalaemia	3. Proportion of hospitalised patients/ED attenders with documented hyperkalaemia, receiving RAASi for prognostic benefit who experience RAASi dose reduction/withdrawal, assessed at discharge	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of repeated episodes of hyperkalaemia	Incidence of repeated episodes of hyperkalaemia after initial episode.	12 months
RAASi discontinuation due to other causes rather than hyperkalaemia	Proportion of patients discontinuing RAASi due to other causes than hyperkalaemia (hypotension, worsening renal function, other).	12 months
Mortality	Number and causes (all cause, cardiovascular or HF) of mortality at 12 months.	12 months
Hospitalisations	Number and causes (all cause, cardiovascular or HF) of hospitalisation at 12 months.	12 months
Hyperkalaemia level at which healthcare professionals make changes to RAASi	Level of hyperkalaemia at which healthcare professionals reduce/stop RAASi in patients with and without clear prognostic indications for RAASi.	12 months
Description of healthcare professionals making changes to RAASi after episodes of hyperkalaemia	Proportion of different grades and specialties of healthcare professionals reducing dose/stopping RAASi in hyperkalaemic patients.	12 months
Awareness of RAASi benefits and target doses for patients with HFrEF	Proportion of different grades and specialties of healthcare professionals who are aware of RAASi target doses and benefits in HFrEF.	12 months

Collaborators and Investigators

• Sponsor: Portsmouth Hospitals NHS Trust
• Collaborators: Vifor Pharma
• Investigators: Principal Investigator: Paul R Kalra, Professor, Queen Alexandra Hospital, Portsmouth, UK

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Anticipated): April 30, 2024
• Study Completion (Anticipated): April 30, 2025

Study Registration Dates

• First Submitted: January 29, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Actual): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 10, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Heart failure with reduced ejection fraction; Hyperkalaemia; Left Ventricular Systolic Dysfunction; Renin-angiotensin-aldosterone system inhibitors; Decision making process; Hyperkalaemia due to RAASi
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Water-Electrolyte Imbalance; Heart Murmurs; Ventricular Dysfunction; Heart Failure; Systolic Murmurs; Hyperkalemia; Ventricular Dysfunction, Left
• Other Study ID Numbers: PHT/2020/11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan to share IDP

Drug and device information, study documents

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