Real-world Study on Dapagliflozin Usage in Patients With Heart Failure (HF) in Germany (EvolutionHF-DE)

Early Treatment of Heart Failure: a Non-interventional Study Program of Patients With Heart Failure and Initiated on Dapagliflozin (EVOLUTION-HF DEallEF)

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). Dapagliflozin was recently granted approval for heart failure by the European Commission, regardless of ejection fraction and whether the patient has diabetes. Real-world observational data are necessary to describe dapagliflozin use in real-world settings in order to assess treatment patterns, HF symptoms and their impact on physical limitation, HRQoL and work productivity, as well as health care utilization of patients treated with dapagliflozin in this setting under local treatment standard conditions in Germany.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Diseases; Cardiovascular Diseases; Heart Failure

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

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

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients who have received treatment with dapagliflozin for HF since 14-90 day before entering the study will be eligible for enrolment by either primary or secondary care healthcare professionals from outpatient settings. All treatment decisions (i.e., dose and duration of treatment) will be at the discretion of the patient's healthcare provider. Patients may have discontinued from dapagliflozin prior to enrolment onto the study, as long as their dapagliflozin initiation was ≥14 days and ≤90 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. Patients will only be enrolled after they have given consent to participate in the study. It is at the discretion of the physician whether or not to initiate patients on treatment with dapagliflozin and enrol them in the study.

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 in accordance with the local dapagliflozin product label for symptomatic chronic heart failure (HF) and at timepoint of dapagliflozin initiation with:

  • preserved ejection fraction (HFpEF; EF≥50%) OR mildly reduced ejection fraction (HFmrEF; EF 41-49%)
  • OR reduced ejection fraction (HFrEF EF ≤40%)
• Patient is enrolled within 14 to 90 days following initiation of dapagliflozin
• Signed and dated informed consent prior to enrolment in the study

Exclusion Criteria:

• Patient should not be enrolled if he/she is less than 14 days or more than 90 days following initiation of dapagliflozin
• Prior treatment with dapagliflozin or other SGLT2i treatment
• Initiation of dapagliflozin outside of the local HF label
• Diagnosis of Type 1 diabetes prior to enrolment
• Current or planned participation in a clinical trial using an investigational medical product for treating HF
• Patient is involved in the planning and/or conduction of the study
• Hypersensitivity to dapagliflozin or to any of the excipients listed in the SmPC

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
HFpEF; Adult patients with preserved ejection fraction (HFpEF; EF≥50%) who receive treatment with dapagliflozin in accordance with the local dapagliflozin product label for symptomatic chronic heart failure.
HFmrEF; Adult patients with mildly reduced ejection fraction (HFmrEF; EF 41-49%) who receive treatment with dapagliflozin in accordance with the local dapagliflozin product label for symptomatic chronic heart failure.
HFrEF; Adult patients with reduced ejection fraction (HFrEF; EF ≤40%) who receive treatment with dapagliflozin in accordance with the local dapagliflozin product label for symptomatic chronic heart failure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to other heart failure treatment 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
Number of other heart failure treatment initiation	The number 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
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
Number of glucose lowering medication initiation	The number 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
Number of glucose lowering medication discontinuation	The number of participants who discontinue treatment with glucose lowering medication other than dapagliflozin.	Baseline to 12 months
Time to discontinuation of dapagliflozin	Time from dapagliflozin treatment initiation until the time at which participants stop taking the medication for any reason (from the perspective of the prescriber).	Baseline to 12 months
Reasons for discontinuation of dapagliflozin	Reasons for discontinuation (from the perspective of the prescriber) of patients initiated on dapagliflozin for HF will be described.	Baseline to 12 months
Dose changes of dapagliflozin	The number of participants with doses changes for dapagliflozin	Baseline to 12 months
Number of patients with dapagliflozin treatment interruptions	The number of participants who discontinue treatment with dapagliflozin.	Baseline to 12 month
Treatment switches from dapagliflozin to other SGLT2i	The number of participants who switch from dapagliflozin to another SGLT2i (Sodium-glucose cotransporter-2 inhibitor) treatment for HF.	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Measured at 3, 6, 9 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.	Measured at 3, 6, 9 and 12 months
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. Several summary scores may be calculated including: Total Symptom score (measuring symptom frequency and symptom burden), Physical limitation score (measuring limitations in common physical activities), Clinical Summary score (measure of physical limitations and total symptoms), and an Overall Summary score (measure of physical limitations, total symptoms, HRQoL, and social limitations). Summary scores will be examined at each assessment point during follow-up.	Measured at 3, 6, 9 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The absolute change from baseline in occurrence of depressions in patients initiated on dapagliflozin for HF as captured by the Patient Health Questionnaire-9 (PHQ-9)	The PHQ-9 comprises 9 items that capture depressed mood and anhedonia. It has been validated as a screening tool with good evidence of responsiveness. The PHQ-9 score is obtained by adding the score for each question (total points). PHQ-9 score ≥10 showed a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 have been shown to represent mild, moderate, moderately severe, and severe depression, respectively.	Measured at 3, 6, 9 and 12 months
Healthcare resource utilisation - Number of hospitalisations since dapagliflozin initiation	The number of patients hospitalised will be examined at each assessment point.	Measured at 3, 6, 9 and 12 months
Healthcare resource utilisation - Length of HF-related hospital stay since dapagliflozin initiation	Duration of outpatient clinic visits in days, will be examined at each assessment point.	Measured at 3, 6, 9 and 12 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: March 22, 2024
• First Submitted That Met QC Criteria: March 22, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Dapagliflozin; Real-World; Heart Failure with preserved ejection fraction (HFpEF); Heart Failure with mildly reduced ejection fraction (HFmrEF); Heart Failure with Reduced Ejection Fraction (HFrEF)
• Additional Relevant MeSH Terms: Heart Failure; Heart Diseases; Cardiovascular Diseases
• Other Study ID Numbers: D1699R00050

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

Drug and device information, study documents

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