Non-interventional Study on Guideline Directed Medical Therapy for Patients With Heart Failure (HF) in Germany

Official title

PHenotype-based RApid SEquencing of Guideline-directed Medical Therapy for Heart Failure With Reduced Ejection Fraction (PHRASE-HF): A Multicentre, Prospective, Non-interventional Study to Examine Outcomes of Rapid In-hospital Implementation of GDMT and Its Translation From Discharge Into Routine Care

Overview

Heart failure (HF) is a global public health issue that affects more than 63 million people worldwide. The clinical and economic burden of HF on health care systems is substantial. Heart failure with reduced ejection fraction (HFrEF) represents approximately 50% of the HF patient population.The burden of HF is expected to increase substantially as the population ages, and despite improvements in treatment, hospitalisation and mortality rates remain especially high in HFrEF patients. The current guideline recommendation of directed medical therapy for HFrEF combines four drug classes with proven prognostic benefit: Angiotensin receptor-neprilysin inhibitor (ARNI)/angiotensin converting enzyme inhibitors (ACE I)/angiotensin receptor blockers (ARB), betablockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i). The 2023 ESC (European Society of Cardiology) HF guideline update additionally recommends a rapid in-hospital sequencing approach of guideline-directed medical therapy (GDMT) with frequent physician visits during the first 6 weeks post discharge. Studies investigating the implementation of GDMT in a real-world setting have shown that a significant proportion of patients did not receive the recommended drug combination therapy. Delayed initiation of GDMT contributes to the low number of patients receiving guideline concordant HFrEF therapy, which ultimately may affect patient outcomes. One approach to implement the 2023 ESC guideline updates for heart failure treatment regarding early in-hospital initiation and rapid up-titration of GDMT could be to provide specific training on GDMT recommendations. Such a standardised training is offered to the physicians treating HF patients within selected hospitals of the German Helios hospital network (Helios-GDMT-program). Evidence is needed in order to assess whether in-hospital initiation and up-titration of all phenotype concordant classes of GDMT at hospital discharge can be observed after standardised physician training and whether the GDMT-program implementation also translates into real-world routine outpatient care with respect to use of GDMT and clinical outcomes.

Detailed description

The overall aim of PHRASE-HF is to evaluate the use of GDMT at hospital discharge, the translation of in-hospital implementation and possible maximisation of phenotype-based GDMT into real-world routine outpatient care, HF symptoms, patient reported outcomes (PROs), clinically relevant outcomes (e.g. rehospitalisation, mortality), use of diuretics and concomitant drug classes in patients admitted for in-hospital treatment of HFrEF to sites trained within the Helios-GDMT-program. The analyses will primarily be done in a total study population, and as defined by exploratory objectives in subgroups of interest.

Primary outcome measures

• Proportion of patients treated with HFrEF GDMT [Time frame: Baseline to hospital discharge, on average 6 days after hospitalization/baseline]

Secondary outcome measures (12)

• Number of recommended HF-drug classes [Time frame: Baseline to hospital discharge, on average 6 days after hospitalization/baseline]
• Change of percentage in HFrEF GDMT [Time frame: Baseline to 12 months]
• Change of phenotype-concordant guideline-recommended HF drug classes [Time frame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months]
• Reasons for GDMT adjustments [Time frame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months]
• Reasons for not having guideline-recommended drug classes or doses [Time frame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months]
• Number of outpatient post-discharge visits [Time frame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 3 months]
• Proportion of patients conducting post-discharge visits [Time frame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 3 months]
• Absolute change from baseline in NYHA class [Time frame: Measured at 6 and 12 months]
• Change from Baseline in blood pressure [Time frame: Baseline to 12 months]
• Change from Baseline in heart rate [Time frame: Baseline to 12 months]
• Change from Baseline in electrolyte level [Time frame: Baseline to 12 months]
• Change from Baseline in potassium level [Time frame: Baseline to 12 months]

Eligibility criteria

Inclusion criteria

• Age ≥18 years at the time of signing the informed consent
• Hospitalised in a participating site and receiving full inpatient treatment (at least 24h hospital stay)
• Diagnosis of HFrEF according to the current guidelines of the European Society of Cardiology (ESC) with a left ventricular EF of ≤40% (as measured per echocardiography during the index hospital stay or within 3 months prior to index hospitalisation with available reports from imaging (ejection fraction) at the time of study inclusion)
• Treated with a maximum of 2 of the indicated drug classes (ACE-I/ARNI/ARB, BB, MRA, SGLT2i) according to guideline recommendation (GDMT) at admission.
• Signed and dated written informed consent prior to enrolment in the study
• Willing and capable to fulfil requirements listed in the ICF

Exclusion criteria

• Initial presentation (index hospitalisation) in cardiogenic shock or other kinds of shock
• Status post heart transplantation
• History of intolerance to one or more GDMT drug classes (ACE-I/ARNI/ARB, BB, MRA, SGLT2i) or significant side effects that led to the discontinuation of two or more substances within one drug class (except from ACE-I/ARB, e.g., if 2 different ACE inhibitors triggered cough, but sartans are tolerated, then the patient is not excluded)
• Current or planned participation in a clinical trial
• Decision by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures
• Pregnancy or breast-feeding

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Germany · 6 centers

• Research Site — Berlin
• Research Site — Erfurt
• Research Site — Gifhorn
• Research Site — Leipzig
• Research Site — Schwerin
• Research Site — Wuppertal

Identifiers

NCT: NCT06675552 · D1699R00045

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗