The Effect of Angiotensin Receptor-Neprilysin Inhibition on Cardiac Fibrosis in Patients With HFpEF (ARNICFH)
Primary Purpose
Heart Failure With Preserved Ejection Fraction
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Angiotensin Receptor-Neprilysin Inhibition
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure With Preserved Ejection Fraction
Eligibility Criteria
Inclusion Criteria:
- Signed and dated written informed consent
- Age ≥ 45 years at time of screening
- Preserved systolic left ventricular function, defined by left ventricular ejection fraction (LVEF) ≥ 50%
- NYHA classes II-IV
- H2FPEF score ≥ 6 or HFA-PEFF score ≥ 5
Exclusion Criteria:
- Patients with a known history of angioedema
- History of hypersensitivity to ARNI
- Any prior echocardiographic measurement of LVEF <45%
- Significant congenital heart disease
- Rheumatic valvular heart disease
- Acute coronary syndrome, cardiac surgery, other major cardiovascular surgery
- Probable alternative diagnoses could account for the patient's HF symptoms
- Systolic blood pressure(BP) >180 mm Hg or diastolic BP >120 mm Hg at visit
- Diastolic BP <90 mm Hg at visit 1, or symptomatic hypotension
- Patients with a cardiac pacemaker therapy device
- eGFR <30 ml/min/1.73 m2
- Serum potassium >5.2 mmol/l at visit 1
- Pregnant or nursing women
Sites / Locations
- The first affiliated Hospital of Chongqing Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
HFpEF with ARNI treatment
Control group
Arm Description
Sacubitril/valsartan (ARNI, 100mg bid)
placebo (100mg bid)
Outcomes
Primary Outcome Measures
Extracellular volume [ECV]
Extracellular volume [ECV] assessment by CMR
Secondary Outcome Measures
myocardial infarction, hospitalization for heart failure and death
myocardial infarction, hospitalization for heart failure and all-cause death
Full Information
NCT ID
NCT05089539
First Posted
October 21, 2021
Last Updated
October 21, 2021
Sponsor
Chongqing Medical University
1. Study Identification
Unique Protocol Identification Number
NCT05089539
Brief Title
The Effect of Angiotensin Receptor-Neprilysin Inhibition on Cardiac Fibrosis in Patients With HFpEF
Acronym
ARNICFH
Official Title
The Effect of Angiotensin Receptor-Neprilysin Inhibition on Cardiac Fibrosis in Patients With HFpEF: A Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2021 (Anticipated)
Primary Completion Date
February 1, 2022 (Anticipated)
Study Completion Date
April 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chongqing Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The effectively therapeutic approaches for Heart failure with preserved ejection fraction (HFpEF) remain limited. The PARAGON-HF trial found that Angiotensin Receptor-Neprilysin Inhibition (ARNI) has potential benefits for the management of HFpEF. Nevertheless, the role of ARNI in cardiac fibrosis in HFpEF are still unclear. We will conduct a prospective randomized controlled trial to evaluate the effect of ARNI on cardiac fibrosis in patients with HFpEF by cardiac magnetic resonance (CMR).
Detailed Description
Heart failure with preserved ejection fraction (HFpEF) comprises approximately 50% of all heart failure. The effectively therapeutic approaches for HFpEF remain limited. The PARAGON-HF trial found that Angiotensin Receptor-Neprilysin Inhibition (ARNI) has potential benefits for the management of HFpEF. Nevertheless, the role of ARNI in cardiac fibrosis in HFpEF are still unclear. We will conduct a prospective randomized controlled trial to evaluate the effect of ARNI on cardiac fibrosis in patients with HFpEF by cardiac magnetic resonance (CMR). We will randomly assign 60 patients with HFpEF (NYHA II-IV) class, ejection fraction ≥ 50% and elevated level of natriuretic peptides to receive sacubitril-valsartan (target 100mg bid) or placebo (100mg bid). The primary endpoint is change in extracellular volume [ECV] measured by CMR. The secondary endpoints were 6-minute walking distance(6-WMD), KCCQ, hospitalizations for heart failure, myocardial infarction and death.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Preserved Ejection Fraction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HFpEF with ARNI treatment
Arm Type
Experimental
Arm Description
Sacubitril/valsartan (ARNI, 100mg bid)
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
placebo (100mg bid)
Intervention Type
Drug
Intervention Name(s)
Angiotensin Receptor-Neprilysin Inhibition
Other Intervention Name(s)
Sacubitril/valsartan
Intervention Description
Sacubitril/valsartan [100 mg] bid). Continuous treatment was maintained for at least three months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo [100 mg] bid). Continuous treatment was maintained for at least three months.
Primary Outcome Measure Information:
Title
Extracellular volume [ECV]
Description
Extracellular volume [ECV] assessment by CMR
Time Frame
Before ARNI or placebo treatment and after 3 months of continuous ANRI or palcebo treatment
Secondary Outcome Measure Information:
Title
myocardial infarction, hospitalization for heart failure and death
Description
myocardial infarction, hospitalization for heart failure and all-cause death
Time Frame
After 3 months of continuous ANRI or palcebo treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed and dated written informed consent
Age ≥ 45 years at time of screening
Preserved systolic left ventricular function, defined by left ventricular ejection fraction (LVEF) ≥ 50%
NYHA classes II-IV
H2FPEF score ≥ 6 or HFA-PEFF score ≥ 5
Exclusion Criteria:
Patients with a known history of angioedema
History of hypersensitivity to ARNI
Any prior echocardiographic measurement of LVEF <45%
Significant congenital heart disease
Rheumatic valvular heart disease
Acute coronary syndrome, cardiac surgery, other major cardiovascular surgery
Probable alternative diagnoses could account for the patient's HF symptoms
Systolic blood pressure(BP) >180 mm Hg or diastolic BP >120 mm Hg at visit
Diastolic BP <90 mm Hg at visit 1, or symptomatic hypotension
Patients with a cardiac pacemaker therapy device
eGFR <30 ml/min/1.73 m2
Serum potassium >5.2 mmol/l at visit 1
Pregnant or nursing women
Facility Information:
Facility Name
The first affiliated Hospital of Chongqing Medical University
City
Chongqing
ZIP/Postal Code
400042
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31475794
Citation
Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Dungen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP; PARAGON-HF Investigators and Committees. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019 Oct 24;381(17):1609-1620. doi: 10.1056/NEJMoa1908655. Epub 2019 Sep 1.
Results Reference
background
PubMed Identifier
32221596
Citation
Vaduganathan M, Jhund PS, Claggett BL, Packer M, Widimsky J, Seferovic P, Rizkala A, Lefkowitz M, Shi V, McMurray JJV, Solomon SD. A putative placebo analysis of the effects of sacubitril/valsartan in heart failure across the full range of ejection fraction. Eur Heart J. 2020 Jul 1;41(25):2356-2362. doi: 10.1093/eurheartj/ehaa184.
Results Reference
background
PubMed Identifier
31146820
Citation
van der Meer P, Gaggin HK, Dec GW. ACC/AHA Versus ESC Guidelines on Heart Failure: JACC Guideline Comparison. J Am Coll Cardiol. 2019 Jun 4;73(21):2756-2768. doi: 10.1016/j.jacc.2019.03.478.
Results Reference
background
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The Effect of Angiotensin Receptor-Neprilysin Inhibition on Cardiac Fibrosis in Patients With HFpEF
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