Plasma ExtrAcellular RNAs and Biomarkers of Heart FaiLure During Decongestion: PEARL-HF Study

Active, not recruiting

• Conditions: Congestive Heart Failure
• Interventions: Other: Monitoring on heart failure therapy

• Registration Number: NCT02632656
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

The primary objective is to measure the association between extracellular RNA (ex-RNA) levels in plasma in patients receiving aggressive outpatient therapy for CHF with (1) cardiac remodeling and (2) cardiovascular events. The investigators will follow patients during standard medical therapy for CHF to assess changes in ex-RNA levels in the plasma, and how these are associated with cardiac remodeling (by cardiac imaging) and outcomes.

Detailed Description

Nearly 5 million people in the United States have congestive heart failure (CHF). Although medical therapy such as beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs) and aldosterone antagonists has improved prognosis, the overall rate of hospital admissions has continued to rise in the last decade and the mortality for patients with symptomatic heart failure remains worse than the majority of cancers in this country. Accordingly, significant opportunities exist for the improvement in outcomes of patients with CHF, both from a morbidity and mortality standpoint. Such opportunities may lie in the outpatient medical management of patients with CHF.

In this study, the primary objective is to measure the association between extracellular RNA (ex-RNA) levels in plasma in patients receiving aggressive outpatient therapy for CHF with (1) cardiac remodeling and (2) cardiovascular events. The investigators will follow patients during standard medical therapy for CHF to assess changes in ex-RNA levels in the plasma, and how these are associated with cardiac remodeling (by cardiac imaging) and outcomes.

Study Timeline

• Study Start: 2015-12
• Study First Submitted: 2015-12-11
• Study First Submitted QC: 2015-12-14
• Study First Posted: 2015-12-17
• Status Verified: 2022-07
• Last Update Submitted: 2023-07-20
• Last Update Posted: 2023-07-24
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Age > 21 years of age
2. Left ventricular ejection fraction ≤ 50% (at any time in the past)
3. Symptomatic (NYHA class II-IV) heart failure (as diagnosed by clinician, radiographic images, or abnormal natriuretic peptide level)
4. Hospital admission, Emergency Department visit, or outpatient diuretic escalation of therapy for destabilized HF at least once in the 6 months prior to enrollment

Exclusion Criteria

1. Severe renal insufficiency defined as serum creatinine > 2.5 mg/dl
2. United Organ Network Sharing status 1B for heart transplantation (outpatient inotrope use, LV assist device)
3. Inoperable aortic valvular heart disease
4. Life expectancy <1 year due to causes other than HF such as advanced cancer
5. Cardiac transplantation or revascularization indicated or expected within 6 months
6. Severe obstructive or restrictive pulmonary disease, defined as a forced expiratory volume in 1 sec <1 L (when diagnosed as standard of care)
7. Subject unable or unwilling to provide written informed consent
8. Coronary revascularization (percutaneous coronary intervention or bypass surgery) within the previous 3 months

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with congestive heart failure	Monitoring on heart failure therapy	Patients with congestive heart failure (CHF) who are followed in the hospital or clinic setting, with optimization of medical therapy

Primary Outcome Measures

Name	Time	Method
Time to stroke or transient ischemic attack	24 hours
Time to decompensated heart failure (HF) requiring in-patient admission or ER visit or IV diuretic therapy in the outpatient realm	24 months	• New onset of classic symptoms and signs of destabilized HF, including lower extremity edema, jugular venous distension, bibasilar crackles, orthopnea and paroxysmal nocturnal dyspnea
Time to acute coronary syndrome	24 months	Myocardial infarction
Time to death	24 months
Time to ventricular arrhythmia	24 months	Clinically significant ventricular arrhythmia, defined as ventricular arrhythmia plus one of the following:

Secondary Outcome Measures

Name	Time	Method
Change in left ventricular (LV) end-systolic volume (in %)	12 months
Change in LV ejection fraction (%)	12 months

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States