PRIME HFrEF: Novel Exercise for Older Patients with Heart Failure with Reduced Ejection Fraction

Not Applicable

Recruiting

• Conditions: Heart Failure with Reduced Ejection Fraction
• Interventions: Other: COMBO; Other: PRIME

• Registration Number: NCT05609097
• Lead Sponsor: University of Virginia

Brief Summary

This study is trying to find out whether performing a hybrid aerobic-resistance exercise training program (titled PRIME: Peripheral Remodeling via Intermittent Muscular Exercise) results in better health outcomes than the traditional exercise training program (called COMBO) that is used in individuals with heart failure with reduced ejection fraction (HFrEF). Participants will be randomized (like the flip of a coin) to either PRIME (investigational) or the traditional exercise program (standard of care).

Detailed Description

This study is a two-arm, prospective randomized clinical trial with participants randomized, in a 1:1 ratio to 4 weeks of either standard progressive whole-body aerobic plus resistance training (COMBO) or PRIME training (Phase 1), followed by 8 weeks of progressive whole-body COMBO assigned to all participants (Phase 2). The objective of this study is to determine whether PRIME exercise training can outperform traditional (COMBO) exercise training to improve outcomes in HFrEF patients. The study aims to test 92 HFrEF patients (46 randomized to PRIME and 46 to COMBO training) over a 5-year period. Data will be collected at each visit and patients will return for a 6-month follow up from the date of the final visit.

Study Timeline

• Study First Submitted: 2022-11-01
• Study First Submitted QC: 2022-11-01
• Study First Posted: 2022-11-08
• Study Start: 2023-04-14
• Status Verified: 2024-07
• Last Update Submitted: 2025-03-13
• Last Update Posted: 2025-03-18
• Primary Completion: 2026-11-30
• Study Completion: 2028-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

• Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
• Subjects may be of either sex with age > 65 years.
• Subjects must be diagnosed with HFrEF as per established echocardiographic criteria (New York Heart Association Class II-III) with an ejection fraction <40%.
• Cardiologist approve after thorough chart review and physical examination
• Hemoglobin of at least 10.0 g/dL

Exclusion Criteria

• Progressive worsening of exercise tolerance or dyspnea at rest or on exertion over previous 3-5 days
• Significant ischemia at low exercise intensities (<2 METS or ~50 W)
• Uncontrolled diabetes (HbA1c >10%)
• Acute systemic illness of fever
• Recent embolism (in the 6 weeks)
• Deep Vein Thrombophlebitis
• Active pericarditis or myocarditis
• Severe aortic stenosis (aortic valve area <1.0 cm2)
• Regurgitant valvular heart disease requiring surgery
• Myocardial infarction within previous 3 weeks
• New onset atrial fibrillation (in the last 4 weeks)
• Resting Heart Rate >120bpm

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
COMBO only	COMBO	4 weeks of standard progressive whole-body aerobic plus resistance training (COMBO) followed by 8 weeks continued COMBO training.
PRIME + COMBO	PRIME	PRIME training (Phase 1), followed by 8 weeks of progressive whole-body COMBO training.
PRIME + COMBO	COMBO	PRIME training (Phase 1), followed by 8 weeks of progressive whole-body COMBO training.

Primary Outcome Measures

Name	Time	Method
VO2peak	12 weeks	Change in cardiorespiratory fitness (peak oxygen consumption \[V̇O2peak\]) after 12 weeks of training. The primary null hypothesis will test if mean change in V̇O2peak after 12 weeks of training is the same for subjects who initially undergo 4 weeks of PRIME before undergoing 8 weeks of progressive whole-body COMBO, versus subjects who undergo the whole 12 weeks of progressive COMBO. The alternative hypothesis is that the mean change in V̇O2peak after 12 weeks of training is not the same for subjects who initially undergo 4 weeks of PRIME training before undergoing 8 weeks of progressive COMBO, versus subjects who undergo the whole 12 weeks of progressive COMBO. Secondary endpoints include blood pressure, vascular function \[arterial stiffness, endothelial function (FMD)\] muscle characteristics and histochemistry, blood chemistry, physical fitness testing, quality of life questionnaires, and adherence.

Secondary Outcome Measures

Name	Time	Method
Muscular fitness	40- weeks	Evaluated using 1 repetition maximal strength \[1RM\] measured in kg units
Physical Function	40- weeks	Evaluated by the Senior Fitness Test scores \[SFT\], measured in percentile units.

Trial Locations

Locations (1)

University of Virginia, Department of Kinesiology; 🇺🇸 Charlottesville, Virginia, United States