Treating Heart Dysfunction Related to Cancer Therapy With Sacubitril/Valsartan
Purpose
To determine feasibility of recruitment and tolerability of treatment with sacubitril-valsartan among adult age survivors of cancer diagnosed at or before age 39 who have stage B heart failure.
Conditions
- Heart Failure
- Heart Dysfunction
Eligibility
- Eligible Ages
- Between 18 Years and 120 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Age </= 39 years old at time of cancer diagnosis - Clinical records adequate to determine diagnosis and treatment regimen - Previous anthracycline chemotherapy - Global longitudinal strain <18% and/or - Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal but >/=40% on echocardiogram or cardiac magnetic resonance imaging (MRI) - No symptoms of heart failure (shortness of breath, fatigue, swelling). Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath).
Exclusion Criteria
- -Age <18 years - Inability to obtain consent from patient or legally authorized representative - Active acute or chronic psychiatric illness that in the opinion of the investigator may prevent compliance with study instructions - Limited English or Spanish proficiency that in the opinion of the investigator may prevent understanding the content of the informed consent form or safely completing the study procedures - Participation in another concurrent intervention study within 30 days or treatment with an investigational drug within 5 half-lives prior to randomization - Greater than mild mitral or aortic valve regurgitation/stenosis known pre-cancer therapy - Severe kidney disease (glomerular filtration rate (GFR) <30 milliliters (mL)/minute (min)/1.73 meters squared (m2)) - Chronic hyperkalemia (>5millimoles per liter (mmol/L)) - Evidence of Coronavirus (COVID-19) within the last 60 days or recent (21 days) exposure to close personal contact with COVID-19. - Greater than moderate tricuspid or pulmonary valve regurgitation/stenosis known pre-cancer therapy - Hemodynamically significant congenital heart disease in the opinion of the investigator (not including patent foramen ovale (PFO)/small atrial septal defect (ASD) or small ventricular septal defect (VSD)) - Greater than moderate pericardial effusion - Constrictive cardiomyopathy diagnosed pre-cancer therapy - Family history of genetic cardiomyopathy - Evidence of infiltrative cardiomyopathy - Symptomatic heart disease based on New York Heart Association (NYHA) classification - Allergy to valsartan or sacubitril - Inability to complete cardiac magnetic resonance (CMR) or 6-minute walk test - Inability to measure non-invasive blood pressure and heart rate in the ambulatory/home setting - Pregnant/lactating - History of severe hypersensitivity reactions to gadolinium-based contrast agents (will perform limited cardiac imaging without contrast) - Concomitant use of other angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), aliskiren, non-steroidal anti-inflammatories (NSAIDs) or lithium or the inability to stop these medications for the study
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Supportive Care
- Masking
- Single (Outcomes Assessor)
- Masking Description
- Cardiac magnetic resonance studies will be de-identified and assigned a study number. The identification key will not be available to cardiac magnetic resonance readers so that they are blinded to treatment allocation
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm 1: Sacubitril-valsartan |
Sacubitril-valsartan administered orally twice daily at a maximally tolerate dose (max dose 97mg/103mg twice daily). |
|
|
Experimental Arm 2: Valsartan |
Valsartan administered orally twice daily at a maximally tolerate dose (max dose 160mg twice daily) |
|
|
Experimental Arm 3: Carvedilol |
Administered orally twice daily at a maximally tolerated dose (max dose 25mg twice daily) |
|
Recruiting Locations
Virginia Commonwealth University
Richmond, Virginia 23298
Richmond, Virginia 23298
More Details
- Status
- Recruiting
- Sponsor
- Virginia Commonwealth University
Detailed Description
The current study will test the hypothesis that among adult age survivors of cancer diagnosed at age < 39 years treatment of Stage B heart failure with sacubitril-valsartan is feasible and safe.