Clinical trial NCT06675552: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Disease
Heart Failure
Cardiovascular Disease
Heart Failure, Systolic
Keywords: Heart Failure with Reduced Ejection Fraction (HFrEF)
Guideline Directed Medical Therapy
Real-World Evidence
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-11-05
Enrollment: 438
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Approximately 438 patients with reduced ejection fraction (HFrEF) admitted for in-hospital treatment with a maximum of 2 of the indicated guideline recommended drug classes (ACE-I/ARNI/ARB, BB, MRA, SGLT2i) in the current medication plan are planned to be enrolled consecutively. Recruitment will take place at 5-7 inpatient cardiology departments at Helios hospitals trained by Helios-GDMT-Program throughout Germany.

Brief summary: 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.

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

Primary outcomes:
measure: Proportion of patients treated with HFrEF GDMT
timeFrame: Baseline to hospital discharge, on average 6 days after hospitalization/baseline
Secondary outcomes:
measure: Number of recommended HF-drug classes
timeFrame: Baseline to hospital discharge, on average 6 days after hospitalization/baseline
measure: Change of percentage in HFrEF GDMT
timeFrame: Baseline to 12 months
measure: Change of phenotype-concordant guideline-recommended HF drug classes
timeFrame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months
measure: Reasons for GDMT adjustments
timeFrame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months
measure: Reasons for not having guideline-recommended drug classes or doses
timeFrame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months
measure: Number of outpatient post-discharge visits
timeFrame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 3 months
measure: Proportion of patients conducting post-discharge visits
timeFrame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 3 months
measure: Absolute change from baseline in NYHA class
timeFrame: Measured at 6 and 12 months
measure: Change from Baseline in blood pressure
timeFrame: Baseline to 12 months
measure: Change from Baseline in heart rate
timeFrame: Baseline to 12 months
measure: Change from Baseline in electrolyte level
timeFrame: Baseline to 12 months
measure: Change from Baseline in potassium level
timeFrame: Baseline to 12 months
measure: Change from Baseline in estimated glomerular filtrations rate
timeFrame: Baseline to 12 months
measure: Change from Baseline in serum creatinine concentration
timeFrame: Baseline to 12 months
measure: Number of rehospitalization for heart failure
timeFrame: Hospital Discharge (on average 6 days after hospitalization/baseline) to 12 months
measure: Overall Survival
timeFrame: Baseline to 12 months
measure: CV-specific survival
timeFrame: Baseline to 12 months
measure: Absolute change from baseline in Medication Adherence Report Scale (MARS)-5 questionnaire
timeFrame: Measured at 6 and 12 months
measure: Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
timeFrame: Measured at 6 and 12 months
measure: Absolute change from baseline in PROMIS Global Health 10
timeFrame: Measured at 6 and 12 months
measure: Absolute change from baseline in the Nine-Item Patient Health Questionnaire (PHQ-9)
timeFrame: Measured at 6 and 12 months
measure: Number of diuretics changes
timeFrame: Baseline to 12 months
measure: Number of concomitant medication changes
timeFrame: Baseline to 12 months
Other outcomes:
Locations:
city: Erfurt
country: Germany
facility: Research Site
city: Gifhorn
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Schwerin
country: Germany
facility: Research Site
city: Wuppertal
country: Germany
facility: Research Site
Study officials:
References: