Study of Sacubitril/ValsarTan on MyocardIal OxygenatioN and Fibrosis in Heart Failure With Preserved Ejection Fraction

NCT04128891 | Withdrawn Phase 3

• 1 other identifier: FlindersU
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To assess the effect of ARNI on myocardial deoxygenation at stress and myocardial fibrosis, and correlate this to changes in myocardial systolic and diastolic function in HFpEF patients.

Conditions

Heart Failure With Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• • To study the effects of Sacubitril/Valsartan on microvascular function and ischaemia in HFpEF patients.

  The HFpEF participants on Sacubitril/valsartan with improvement in microvascular function and ischaemia, as assessed by OS-CMR at rest and stress (ΔSI: signal intensity change, at baseline and at 12 months).

  12 Months

Secondary Outcomes (8)

• 2.1 Incidence of microvascular dysfunction in HFpEF

  12 Months

• 2.2 Extent of myocardial fibrosis in HFpEF

  12 Months

• 2.3 Assessment of left ventricular diastolic function in HFpEF

  12 Months

• 2.4 New York Heart Association (NYHA) class

  12 Months

• 2.5 Functional assessment

  12 Months

Study Arms (2)

Sacubitril/Valsartan

EXPERIMENTAL

30 participants to be administered Sacubitril/Valsartan (Entresto) tablets, minimum dose of 49/51mg or maximum dose of 97/103 mg twice daily for the duration of the study (two years).

Drug: Sacubitril-Valsartan

Valsartan

ACTIVE COMPARATOR

30 participants to be administered Valsartan tablets, minimum dose 80 mg or maximum dose of 160 mg twice daily for the duration of the study (two years).

Drug: Sacubitril-Valsartan

Interventions

Sacubitril-Valsartan DRUG

Cardiomagnetic Resonance Imaging

Also known as: Valsartan

Sacubitril/Valsartan; Valsartan

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent will be obtained before any assessment is performed
• ≥ 40 years of age, male or female
• LVEF ≥45% by echocardiography during the screening period
• Symptom(s) of heart failure requiring treatment with diuretic(s) for at least 30 days prior to screening visit
• Current symptom(s) of heart failure (NYHA functional class II to IV)
• Structural heart disease evidenced by at least 1 of the following echocardiography findings:
• Left atrial (LA) enlargement defined by at least 1 of the following: LA width (diameter) ≥3.8 cm or LA length ≥5.0 cm or LA area ≥20 cm2 or LA volume ≥55 ml or LA volume index ≥29 ml/m2
• Left ventricular hypertrophy defined by septal thickness or posterior wall thickness ≥1.2 cm
• Elevated NT-proBNP (atleast 1 of the following)
• NT-proBNP \>300 pg/ml for patients not in atrial fibrillation or \>900 pg/ml for patients in atrial fibrillation during initial screening
• Heart failure hospitalization (defined as heart failure listed as the major reason for hospitalization) within 9 months prior to screening visit and NT-proBNP \>200 pg/ml for patients not in atrial fibrillation or \>600 pg/ml for patients in atrial fibrillation during initial screening

You may not qualify if:

• Any prior echocardiographic measurement of LVEF \<45%
• Acute coronary syndrome (including myocardial infarction), cardiac surgery, other major cardiovascular surgery, or percutaneous coronary intervention within 3 months
• Known unrevascularized epicardial coronary artery disease (\> 50% stenosis in any major epicardial coronary artery)
• Current acute decompensated heart failure requiring augmented therapy with intravenous diuretic agents, vasodilator agents, and/or inotropic drugs
• Patients who require treatment with 2 or more of the following: an angiotensin converting enzyme inhibitor, an angiotensin receptor blocker, or a renin inhibitor
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
• Patients with a known history of angioedema
• Probable alternative diagnoses that in the opinion of the investigator could account for the patient's heart failure symptoms such as significant pulmonary disease (including primary pulmonary hypertension), anaemia, or obesity. Specifically, patients with the following are excluded:
• Severe pulmonary disease including chronic obstructive pulmonary disease (i.e., requiring home oxygen therapy, chronic oral steroid therapy or hospitalized for pulmonary decompensation within 12 months) or
• Haemoglobin \<10 g/dl, or
• Body mass index \>40 kg/m2
• Patients with any of the following:
• Systolic blood pressure (SBP) ≥180 mm Hg at entry, or
• SBP \>150 mm Hg and \<180 mm Hg at entry unless the patient is receiving 3 or more antihypertensive drugs.
• SBP \<110 mm Hg at entry

Sponsors & Collaborators

• Flinders University: lead

Related Publications (38)

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MeSH Terms

Interventions

sacubitril and valsartan sodium hydrate drug combination; Valsartan

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Carmine De Pasquale, Assoc Prof

  Flinders Medical Centre

  PRINCIPAL INVESTIGATOR

• Majo Joseph, Doctor

  Flinders Medical Centre

  PRINCIPAL INVESTIGATOR

• Rajiv Ananthakrishna, Doctor

  Flinders Medical Centre

  PRINCIPAL INVESTIGATOR

• Michael Stokes, Doctor

  Royal Adelaide Hospital

  PRINCIPAL INVESTIGATOR

• Sean Lal, Doctor

  Royal Prince Alfred

  PRINCIPAL INVESTIGATOR

• David Kaye, Professor

  Baker Institute/ Alfred Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: October 16, 2019
• Study Start: February 1, 2020
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2024
• Last Updated: August 30, 2021

Record last verified: 2021-08