Exercise-Based Cardiac Rehabilitation for Patients With Heart Failure With Preserved Ejection Fraction (EMPOWER-HFpEF)

NCT07727096 | Not Yet Recruiting DMC

• 1 other identifier: EMPOWER-HFpEF
• Study Type: interventional
• Target: 390
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure with preserved ejection fraction (HFpEF) is a common condition among older adults. It is associated with frequent hospitalizations, impaired functional capacity, reduced quality of life, and high healthcare utilization. Despite recent advances in pharmacological therapy, many patients continue to experience recurrent clinical deterioration and functional decline. Exercise-based cardiac rehabilitation has demonstrated benefits in improving physical performance and quality of life. Still, its effect on long-term clinical outcomes in patients with high-risk HFpEF has not been established. The EMPOWER-HFpEF study is a multicenter, randomized, controlled trial designed to evaluate whether an early, individualized, multimodal exercise-based cardiac rehabilitation program improves clinical outcomes compared with usual care in patients with HFpEF. Eligible participants will be randomly assigned in a 1:1 ratio to receive either usual care alone or usual care plus a structured 12-month exercise-based cardiac rehabilitation program. The intervention includes an initial 6-month supervised phase, followed by a 6-month hybrid phase combining supervised sessions with structured home- or community-based exercise to promote long-term adherence and maintenance of physical activity. The primary objective is to determine whether this rehabilitation strategy reduces adverse clinical outcomes, including all-cause mortality, heart failure hospitalizations, all-cause hospitalizations, and outpatient heart failure decompensation, while improving functional capacity and health-related quality of life over 12 months. The results of this study will provide evidence on the effectiveness of a long-term multimodal exercise-based cardiac rehabilitation program as part of the comprehensive management of patients with HFpEF.

Conditions

HF - Heart Failure; HFpEF - Heart Failure With Preserved Ejection Fraction; Readmission Rates; Exercise Training; Cardiac Rehab

Keywords

Heart Failure with Preserved Ejection Fraction; Cardiac Rehabilitation; Quality of Life; Readmission

Outcome Measures

Primary Outcomes (1)

• Hierarchical composite clinical outcome (win ratio)

  Comparison between treatment groups using a hierarchical composite endpoint analyzed according to the win ratio method. The hierarchical endpoint includes, in order of priority, all-cause mortality, heart failure hospitalization, all-cause hospitalization, outpatient heart failure decompensation without hospitalization, days alive and out of hospital, change in physical function assessed by the Short Physical Performance Battery (SPPB; total score range 0-12, with higher scores indicating better physical function), and change in health-related quality of life assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS; score range 0-100, with higher scores indicating better health status).

  12 months

Secondary Outcomes (5)

• All-Cause Mortality

  12 months

• Heart Failure Hospitalization or Outpatient Heart Failure Decompensation

  12 months

• All-Cause Hospitalization

  12 months

• Health-Related Quality of Life

  Baseline and 12 months

• Physical Function

  Baseline and 12 months

Other Outcomes (7)

• Peak Oxygen Uptake

  Baseline and 12 months

• Left Ventricular Diastolic Function

  Baseline and 12 months

• Right Ventricular Systolic Function

  Baseline and 12 months

Study Arms (2)

Guideline-Directed Medical Therapy

ACTIVE COMPARATOR

Participants receive guideline-directed medical therapy, regular follow-up in the heart failure clinic, lifestyle education, and individualized recommendations for home-based physical activity, in accordance with current clinical practice.

Other: Guideline-Directed Medical Therapy

Exercise-Based Cardiac Rehabilitation

EXPERIMENTAL

Participants receive guideline-directed medical therapy plus a structured 12-month exercise-based cardiac rehabilitation program consisting of a 6-month supervised phase followed by a 6-month hybrid supervised and home-based phase.

Behavioral: Exercise-Based Cardiac Rehabilitation; Other: Guideline-Directed Medical Therapy

Interventions

Exercise-Based Cardiac Rehabilitation BEHAVIORAL

A structured, individualised, multimodal exercise-based cardiac rehabilitation program delivered over 12 months. The intervention includes aerobic exercise, resistance training, inspiratory muscle training, and lifestyle counselling. It consists of an initial 6-month supervised phase, followed by a 6-month hybrid phase that combines supervised and home-based exercise to promote long-term adherence and maintenance of physical activity.

Exercise-Based Cardiac Rehabilitation

Guideline-Directed Medical Therapy OTHER

Participants receive guideline-directed medical therapy according to current heart failure guidelines, regular follow-up in the heart failure clinic, lifestyle education, and individualized recommendations to maintain regular physical activity as part of routine clinical care.

Exercise-Based Cardiac Rehabilitation; Guideline-Directed Medical Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 years or older.
• Diagnosis of heart failure with preserved ejection fraction (HFpEF) according to current clinical guidelines, defined by: a) signs and/or symptoms of heart failure; b) left ventricular ejection fraction ≥50%; c) elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) (≥220 pg/mL); and, d) objective evidence of structural and/or functional cardiac abnormalities consistent with HFpEF.
• High-risk clinical profile, defined by at least one of the following: a) hospitalization for acute or worsening heart failure within the previous 120 days; b) outpatient worsening heart failure within the previous 120 days requiring emergency department evaluation or intensification of oral or intravenous diuretic therapy in a specialized heart failure clinic; c) recent diagnosis of symptomatic HFpEF (≤120 days) with New York Heart Association (NYHA) functional class II-III; or d) stable symptomatic HFpEF (NYHA class II-III) with at least two of the following comorbidities: hypertension, diabetes mellitus, obesity (body mass index ≥30 kg/m²), chronic kidney disease, dyslipidemia, obstructive sleep apnea, or stable coronary artery disease, together with elevated NT-proBNP (≥220 pg/mL in patients in sinus rhythm or ≥600 pg/mL in patients with atrial fibrillation).
• Clinically stable at the time of enrollment, with no requirement for intravenous therapy or major changes in heart failure treatment during the previous 2 weeks.
• Considered by the investigator to be able to participate in a structured exercise-based cardiac rehabilitation program safely.
• Able and willing to provide written informed consent before any study-specific procedures.

You may not qualify if:

• Inability to safely participate in a structured exercise-based cardiac rehabilitation program because of severe neurological or musculoskeletal disorders, significant cognitive impairment, or severe psychiatric illness that, in the opinion of the investigator, would interfere with study participation.
• Clinically unstable heart failure at the time of enrollment, defined by the need for intravenous therapy, recent major changes in heart failure treatment, or ongoing heart failure decompensation.
• Severe valvular heart disease considered to be the primary cause of the patient's symptoms.
• Acute coronary syndrome, unstable angina, or coronary revascularization within the previous 2 weeks.
• Uncontrolled hypertension, defined as resting systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg, or resting heart rate ≥110 beats/min despite guideline-directed medical therapy.
• Severe primary pulmonary disease predominantly limiting functional capacity, including significant pulmonary hypertension, chronic thromboembolic pulmonary disease, or severe chronic obstructive pulmonary disease.
• Primary cardiomyopathy or known infiltrative heart disease.
• Severe non-cardiac comorbidity associated with an estimated life expectancy of less than 1 year, in the opinion of the investigator.
• Inability to provide written informed consent or to comply with study procedures and follow-up requirements.

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead
• Generalitat Valenciana: collaborator

Study Sites (1)

INCLIVA

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Central Study Contacts

Patricia Fernández Saiz, PhD

CONTACT

96 162 89 18; patricia.fernandez@incliva.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: No additional parties are masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2026
• First Posted: July 27, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2031
• Last Updated: July 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: De-identified individual participant data and supporting documents will be considered for sharing following publication of the primary study results, for a period to be determined in accordance with institutional policies and applicable regulations.
• Access Criteria: Access to de-identified individual participant data and supporting documentation will be considered upon reasonable request. Requests will be reviewed on a case-by-case basis by the study investigators in accordance with institutional policies, ethical requirements, and applicable legal and regulatory frameworks. Access may require a data sharing agreement

Locations

ES (1)