Effect of Sacubitril-Valsartan on Cardiac Structure and Function

Effect of Sacubitril-Valsartan on Cardiac Structure and Function in Adults With Congenital Heart Disease

The purpose of this study is to compare changes in cardiac structure and function, biomarkers, and patient reported outcomes between adults with congenital heart disease (ACHD) randomized to angiotensin receptor-neprilysin inhibitor (ARNI) therapy vs placebo.

Study Overview

• Status: Recruiting
• Conditions: Congenital Heart Disease
• Intervention / Treatment: Drug: Entresto Pill; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Amanda Wozniak; Phone Number: 507-266-1976; Email: Wozniak.Amanda@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Amanda Wozniak; Phone Number: 507-266-1976; Email: Wozniak.Amanda@mayo.edu
      • Principal Investigator: Alexander C Egbe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Congenital Heart Disease Diagnosis
• Age 18 or Older

Exclusion Criteria:

• Stage IV chronic kidney disease defined as creatinine clearance <30 ml/min
• Hyperkalemia defined as serum potassium >5.2 mmol/l,
• Hypotension defined as systolic blood pressure <100 mmHg,
• History of angioedema related to previous ACE or ARB therapy
• Patients diagnosed with diabetes using Aliskiren,
• Pregnancy.

• Drug Therapies

  • Amifostine
  • Droperidol
  • Dantrolene
  • CYP3A4 Inhibitors
  • Obinutuzumab
  • Aliskiren
  • Lithium
  • Sparsentan
  • ACE inhibitor
  • ARB
  • ARNI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Patients taking placebo tablets will take 1 tablet orally, twice daily
Experimental: Entresto	Drug: Entresto Pill; Patients will take a 24/26 mg dose orally, twice daily, for weeks 1 and 2, 49/51 mg orally, twice daily, for weeks 3 and 4, and 97/103 mg orally twice daily, for the remaining 48 weeks (total duration: 52 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventricular function	Ventricular Function will be determined by indices of Right Ventricle (RV) and Left Ventricle (LV) systolic and diastolic function indices acquired from CMRI and transthoracic echocardiographic imaging.	Baseline, Week 52
Change from baseline in Hs-Troponin	Hs-Troponin will be determined by blood specimen and will be measured in ng/L. A higher value indicates damage to the heart.	Baseline, Week 52
Change from baseline in Galectin 3	Galectin 3 will be determined by blood specimen and will be measure in ng/mL. A higher value indicates a higher severity of heart disease.	Baseline, Week 52
Change from baseline in Cystatin C	Cystatin C will be determined by blood specimen and measured in mg/L. A lower value reflects better kidney function.	Baseline, Week 52
Change in baseline in Soluble ST-2 (sST-2)	Soluble ST-2 (sST-2) will be determined by blood specimen and measured in ng/mL. A higher value indicates a higher severity of heart failure.	Baseline, Week 52
Patient reported outcomes	Patient reported outcomes will be determined by a quality-of-life questionnaire. A self-assessment survey to assess the extent to which heart failure (HF) affects the patient's activities of daily living and quality of life. The questionnaire is 12 questions and a lower score reflects more severe the limitations on daily life.	Baseline, Week 52
Ventricular structure	Ventricular structure will be determined by Right Ventricle (RV) and Left Ventricle (LV) size and wall thickness acquired from CMRI and transthoracic echocardiographic imaging.	Baseline, Week 52

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Alexander Egbe, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Actual): November 18, 2024

Study Record Updates

• Last Update Posted (Estimated): October 7, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Defects, Congenital; Molecular Mechanisms of Pharmacological Action; Angiotensin Receptor Antagonists; sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: 24-009099; 5R01HL162830-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No