Treating Heart Dysfunction Related to Cancer Therapy With Sacubitril/Valsartan (TREAT-HF)

Treating Heart Dysfunction Related to Cancer Therapy With Sacubitril/Valsartan (Treat HF)

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Heart Dysfunction
• Intervention / Treatment: Drug: Sacubitril-valsartan; Drug: Valsartan; Drug: Carvedilol

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 Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Massey CTO CPC Team; Phone Number: 804-628-6430; Email: MasseyCPC@vcu.edu

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
      • Principal Investigator: Wendy Bottinor, MD
      • Contact: Massey CTO CPC Team; Phone Number: 804-628-6430; Email: MasseyCPC@vcu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Sacubitril-valsartan; Sacubitril-valsartan administered orally twice daily at a maximally tolerate dose (max dose 97mg/103mg twice daily).	Drug: 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)	Drug: 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)	Drug: Carvedilol; Administered orally twice daily at a maximally tolerated dose (max dose 25mg twice daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Number of participants screened for the clinical trial.	24 Months
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.	Number of participants enrolled on the trial	27 Months
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.	Number of participants that complete therapy	27 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	Number of deaths while on study due to cardiac event	27 Months
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	Number of deaths while on study due to non-cardiac events	90 Days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By the number of Adverse events at 60 days	60 Days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By determining number of participants with interval change utilizing a 6-minute walk test distance	90 Days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By the number of Adverse events at 30 days	30 Days after start of treatment
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By the number of Adverse events at 180 days	180 Days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By the number of Adverse events at 270 days	270 Days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By the number of Adverse events at 365 days	365 Days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By determining number of participants with interval change utilizing a 6-minute walk test distance	Baseline, Day 60 days, 365 Days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By number of participants with cardiovascular magnetic resonance imaging assessment change in cardiac fibrosis burden.	Baseline, 90 Days, 365 Days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By number of participants with cardiovascular magnetic resonance imaging assessment change in microvascular perfusion.	Baseline, 90 Days, 365 days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By number of participants with cardiovascular magnetic resonance imaging assessment change in arterial stiffness/4D flow.	Baseline, 90 Days, 365 days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By number of participants with cardiovascular magnetic resonance imaging assessment change in left ventricular ejection fraction.	Baseline, 90 Days, 365 days
Evaluate early efficacy of sacubitril-valsartan in the treatment of stage B heart failure among survivors of cancer diagnosed at or before age 39.	By number of participants with cardiovascular magnetic resonance imaging assessment change in change in left ventricular strain.	Baseline, 90 Days, 365 Days

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Wendy Bottinor, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2022
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: January 3, 2022
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Amines; Indoles; Amino Acids; Alcohols; Propanolamines; Amino Alcohols; Propanols; Amino Acids, Essential; Heterocyclic Compounds, 3-Ring; Tetrazoles; Carbazoles; Valine; Amino Acids, Branched-Chain; Valsartan; Carvedilol; sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: MCC-21-18830; HM20023601 (Other Identifier: Virginia Commonwealth University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are no plans to make individual participant data available to other researchers at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No