Real-world Dapagliflozin Treatment in Patients With Heart Failure in Portugal (EVOLUTION-HF) (EVOLUTION-HF)

Early Treatment of Heart Failure: a Non-interventional Observational Study of Patients With Heart Failure and Initiated on Dapagliflozin in Portugal

Heart failure (HF) is a global, public health issue that affects more than 63 million people worldwide; this burden is expected to increase substantially as the population ages. Despite advancements in treatment, a HF diagnosis still leads to significant morbidity and mortality; there is also an immense impact on patients' health-related quality of life (HRQoL). On May 5, 2020, the US Food and Drug Administration (FDA) announced the approval of dapagliflozin for heart failure with reduced ejection fraction (HFrEF), regardless of whether the patient has diabetes. Subsequently, there have been additional approvals for this indication by regulatory authorities across the globe." Real-world observational data are necessary to describe dapagliflozin use in real-world settings with detailed clinical data on heart failure symptoms, outcomes, and HRQoL.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure

Detailed Description

Heart failure (HF) is a global, public health issue that affects more than 63 million people worldwide; this burden is expected to increase substantially as the population ages. Despite advancements in treatment, a HF diagnosis still leads to significant morbidity and mortality; there is also an immense impact on patients' health-related quality of life (HRQoL). On May 5, 2020, the US Food and Drug Administration (FDA) announced the approval of dapagliflozin for heart failure with reduced ejection fraction (HFrEF), regardless of whether the patient has diabetes. Subsequently, there have been additional approvals for this indication by regulatory authorities across the globe." Real-world observational data are necessary to describe dapagliflozin use in real-world settings with detailed clinical data on heart failure symptoms, outcomes, and HRQoL. EVOLUTION-HF will help obtaining relevant insights from clinical practice through the analysis of detailed data on heart failure symptoms/severity for patients receiving dapagliflozin in real-world setting.

Study aims are to describe the characteristics of patients newly prescribed dapagliflozin for the treatment of HFrEF, to provide early insights into real-world dapagliflozin treatment patterns, and to describe patients-reported outcomes, medication adherence and work productivity losses in these patients.

This observational, longitudinal cohort study will include patients with a physician diagnosis of HFrEF who are initiated on dapagliflozin in clinical practice. The study will include 2 cohorts of patients: one fully retrospective and one prospective cohort, in which patient-reported outcomes (PROs) including quality of life will be collected

• Study Type: Observational
• Enrollment (Actual): 287

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Portugal
  • Almada, Portugal
    • Research Site
  • Amadora, Portugal
    • Research Site
  • Coimbra, Portugal
    • Research Site
  • Lisboa, Portugal
    • Research Site
  • Penafiel, Portugal
    • Research Site
  • Porto, Portugal
    • Research Site
  • Setubal, Portugal
    • Research Site
  • Vila Real, Portugal
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with registered hospital diagnosis of HF who have received treatment with dapagliflozin for HFrEF will be eligible for enrolment by physicians from both outpatient and inpatient settings. In all cases, the decision to treat a patient with dapagliflozin must be made prior to the decision to enrol the patient into the study. To help ensure this, patients cannot be enrolled <30 days after starting dapagliflozin treatment. Therefore, the earliest date at which all data collected directly from patients such as PROs may be captured is 30 days following initiation of dapagliflozin. Patients may have discontinued from dapagliflozin prior to enrolment onto the study, as long as their dapagliflozin initiation was ≥30 days and ≤60 days prior to enrolment onto the study. Data on other parameters may be obtained at the date of initiation of dapagliflozin by extracting this information retrospectively from medical charts.

Description

Inclusion Criteria:

• Age ≥18 years as of study index date; the study index date is date of initiation of treatment with dapagliflozin

• Patient received/receiving treatment with dapagliflozin for HFrEF (EF ≤40%) in accordance with the local dapagliflozin product label:

  • Retrospective study: their dapagliflozin initiation was between 1st of March 2021 and 31st of October 2021.
  • Prospective study: their dapagliflozin initiation was ≥30 days and ≤60 days prior to enrollment onto the study
• Signed and dated informed consent prior to enrollment in the study (only applicable for the prospective cohort, informed consent waiver will be requested for retrospective cohort)

Exclusion Criteria:

• Patient is enrolled less than 30 days following initiation of dapagliflozin
• Prior treatment with dapagliflozin or other SGLT2i treatment
• Initiation of dapagliflozin outside of local HF label
• Diagnosis of Type 1 diabetes prior to enrolment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Retrospective cohort; Patients who have initiated treatment with dapagliflozin for HFrEF between 1st of March 2021 and 31st of October 2021 (prior to study initiation date).
Prospective Cohort; Patients who have started treatment with dapagliflozin for HFrEF from 1st April 2022 onwards. At least 30 days must have elapsed (but no more than 60 days) from first prescription of dapagliflozin before a patient can be enrolled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to dapagliflozin treatment discontinuation	Time from dapagliflozin treatment initiation until the time at which participants stop taking the medication for any reason.	Baseline to 12 months
Proportion of reasons for dapagliflozin treatment discontinuation	Proportion of reasons for dapagliflozin treatment discontinuation as noted by a health care professional will extracted and described as the number and proportion of participants who have discontinued dapagliflozin according to each reasons presented.	Baseline to 12 months
Number of dapagliflozin treatment changes	The number of participants who switch to another HF medication other than dapagliflozin.	Baseline to 12 months
Percentage of dapagliflozin treatment changes	The percentage of participants who switch to another HF medication other than dapagliflozin.	Baseline to 12 months
Number of dapagliflozin treatment discontinuation	The number of participants who discontinued treatment with dapagliflozin.	Baseline to 12 months
Percentage of dapagliflozin treatment discontinuation	The percentage of participants who discontinued treatment with dapagliflozin.	Baseline to 12 months
Number of other heart failure treatment initiation	The number of participants who initiate new heart failure medication other than dapagliflozin.	Baseline to 12 months
Percentage of other heart failure treatment initiation	The percentage of participants who initiate new heart failure medication other than dapagliflozin.	Baseline to 12 months
Number of other heart failure treatment dosage changes	The number of participants with dosage changes for heart failure medication other than dapagliflozin.	Baseline to 12 months
Percentage of other heart failure treatment dosage changes	The percentage of participants with dosage changes for heart failure medication other than dapagliflozin.	Baseline to 12 months
Number of other heart failure treatment discontinuation	The number of participants who discontinue treatment with heart failure medication other than dapagliflozin.	Baseline to 12 months
Percentage of other heart failure treatment discontinuation	The percentage of participants who discontinue treatment with heart failure medication other than dapagliflozin.	Baseline to 12 months
Number of glucose lowering medication initiation	The number of participants who initiate new glucose lowering medication other than dapagliflozin.	Baseline to 12 months
Percentage of glucose lowering medication initiation	The percentage of participants who initiate new glucose lowering medication other than dapagliflozin.	Baseline to 12 months
Number of glucose lowering medication dosage changes	The number of participants with dosage changes for glucose lowering medication other than dapagliflozin.	Baseline to 12 months
Percentage of glucose lowering medication dosage changes	The percentage of participants with dosage changes for glucose lowering medication other than dapagliflozin.	Baseline to 12 months
Number of glucose lowering medication discontinuation	The number of participants who discontinue treatment with glucose lowering medication other than dapagliflozin.	Baseline to 12 months
Percentage of glucose lowering medication discontinuation	The percentage of participants who discontinue treatment with glucose lowering medication other than dapagliflozin.	Baseline to 12 months
Number of reasons for dapagliflozin treatment discontinuation	Number of reasons for dapagliflozin treatment discontinuation as noted by a health care professional will be extracted and described as the number and proportion of participants who have discontinued dapagliflozin according to each reasons presented.	Baseline to 12 months
Time to other HF medication discontinuation	Time from initiation of heart failure medication other than dapagliflozin until the time at which participants discontinued treatment with that medication.	Baseline to 12 months
Time to glucose lowering medication discontinuation	Time from initiation of glucose lowering medication until the time at which participants discontinued treatment with that medication.	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) score	The KCCQ is a 23-item questionnaire that quantifies physical limitations, self-efficacy, social interference and quality of life. Summary scores will be examined at each assessment point during follow-up. For each of the assessment periods, descriptive statistics for the observed value, change from baseline and the 95% two-sided confidence interval for the mean change will be presented. The proportions of participants with overall health status classified as poor, fair, good, and excellent will be examined at each assessment point. Additionally, the proportions of participants who experience clinically meaningful changes in overall health status: improvement (≥5 point increase), deterioration (≥5 point decrease), and stable (<5 point increase or decrease) will be examined at each assessment point. Only applicable to Prospective cohort.	Measured at 3, 6 and 12 months
Absolute change from baseline in Medication Adherence Report Scale (MARS)-5 questionnaire	The MARS-5 is five-item self-report adherence scale which assesses both intentional and non-intentional non-adherence. Respondents rate the frequency with which the five different medication-taking behaviours occur, scoring each item on a 1-5-point scale with higher scores indicating higher reported adherence. The MARS-5 has been shown to be reliable and valid across a variety of health conditions, including cardiovascular and pulmonary diseases. Only applicable to Prospective cohort.	Measured at 3, 6 and 12 months
Absolute change from baseline in Work Productivity and Activity Impairment (WPAI) score	The WPAI is a validated instrument to measure impairments in paid and unpaid work and activities. It measures absenteeism (work time missed), presenteeism (impairment at work / reduced on-the-job effectiveness) as well as the impairments in unpaid activity because of health problems during the past seven days. It has been validated to quantify work impairments for numerous diseases such as asthma, psoriasis, irritable bowel syndrome, and Crohn's disease, but has not yet been validated for use in heart failure participants. Scores will be derived from the overall work impairment at each timepoint and then changes of from baseline will be reported. Only applicable to Prospective cohort.	Measured at 3, 6 and 12 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2022
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: June 28, 2022
• First Submitted That Met QC Criteria: July 15, 2022
• First Posted (Actual): July 19, 2022

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Heart Failure; Dapagliflozin; Heart Failure with Reduced Ejection Fraction; HFrEF; Real-world
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: D1699R00036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

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