Treating Heart Dysfunction Related to Cancer Therapy With Sacubitril/Valsartan

Phase 1

Recruiting

• Conditions: Heart Failure; Heart Dysfunction
• Interventions: Drug: Sacubitril-valsartan; Drug: Valsartan

• Registration Number: NCT05194111
• Lead Sponsor: Virginia Commonwealth University

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2022-01-03
• Study First Submitted QC: 2022-01-03
• Study First Posted: 2022-01-18
• Study Start: 2022-08-11
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-21
• Primary Completion: 2025-11-30
• Study Completion: 2025-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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
• L VEF below the institutional lower limit of normal but >/=40% on echocardiogram or cardiac 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 (GFR <30 mL/min/1.73m2)
• Chronic hyperkalemia (>5mmol/L)
• Evidence of 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 PFO/small ASD or small 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 NYHA classification
• Allergy to valsartan or sacubitril
• Inability to complete 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 ACE inhibitors or ARBs, aliskiren, NSAIDs or lithium or the inability to stop these medications for the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Sacubitril-valsartan	Sacubitril-valsartan	Sacubitril-valsartan administered orally twice daily at a maximally tolerate dose (max dose 97mg/103mg twice daily).
Arm 2: Valsartan	Valsartan	Valsartan administered orally twice daily at a maximally tolerate dose (max dose 160mg twice daily)

Primary Outcome Measures

Name	Time	Method
Determine feasibility of recruitment to this pilot trial by evaluating the eligibility requirements among adult age survivors of cancer diagnosed at or before age 39 who have stage B heart failure.	24 Months	Number of participants screened for the clinical trial.
Determine the feasibility of recruitment to this pilot trial by evaluating the eligibility requirements among adult age survivors of cancer diagnosed at or before age 39 who have stage B heart failure.	27 Months	Number of participants enrolled on the trial
Determine tolerability of treatment with sacubitril-valsartan among adult age survivors of cancer diagnosed at or before age 39 who have stage B heart failure.	27 Months	Number of participants that complete therapy

Secondary Outcome Measures

Name	Time	Method
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	90 Days	By number of participants with cardiovascular magnetic resonance imaging assessment change in change in left ventricular strain.

Trial Locations

Locations (1)

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States