Heart Failure and Reduced Ejection Fraction Clinical Trial
— EVALUATE-HFOfficial title:
A Multicenter, Randomized, Double-blind, Double-dummy, Parallel Group, Active-controlled, Forced-titration, 12-week Comparison of Combined Angiotensin-neprilysin Inhibition With Sacubitril and Valsartan Versus Enalapril on Changes in Central Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction (HFrEF)
| Verified date | March 2020 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
To determine whether treatment with sacubitril/valsartan provides a superior effect on aortic characteristic impedance compared to enalapril in patients with heart failure and reduced ejection fraction (left ventricular ejection fraction [LVEF] ≤ 40%) after 12 weeks of treatment. The primary endpoint is the change in aortic characteristic impedance (Zc = dP/dQ in early systole) between baseline and Week 12.
| Status | Completed |
| Enrollment | 465 |
| Est. completion date | January 26, 2019 |
| Est. primary completion date | December 13, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 50 Years and older |
| Eligibility | Inclusion Criteria: - History of HTN and one of the following at BOTH screening and pre-randomization: 1. SBP >105 mm Hg on antihypertensive medication. 2. SBP >/= 140 mm Hg and NOT on antihypertensive medication. - NYHA class I-III heart failure and with reduced ejection fraction </= 40%, as determined by any local measurement made within the past 12 months using echocardiography, MUGA, CT scanning, MRI, ventricular angiography or single-photon emission computed tomography (SPECT), provided no subsequent measurement above 40%. Patients who have had an intervening medical event (e.g. myocardial infarction) or procedure (e.g. revascularization, cardiac resynchronization), must have a reassessment of EF = 3 months following the event to ensure that eligibility criteria are still met. - On stable doses of treatment with guideline-directed therapy, other than ACEis and ARBs prior to randomization. 1. If the patient is currently taking an ACEi, a 36-hour washout is required prior to randomization (Visit 2). 2. If the patient is currently taking an ARB, they must discontinue the ARB before initiation of study treatment however washout is not required. - On an optimal medical regiment of diuretics and background medications to effectively treat co-morbidities such as HTN, DM, and coronary artery disease. Key Exclusion Criteria: - History of hypersensitivity to any of the study drigs, including history of hypersensitivity to drugs of similar chemical classes, or allergy to ACEis, ARBs, or NEP inhibitors as well as known or suspected contraindications to the study drugs. - Previous history of intolerance to sacubitril and valsartan, ACEi or ARB standard of care doses despite appropriate and gradual up-titration. - History of angioedema, drug-related or otherwise. - Requirement of treatment with both ACE inhibitor and ARB. - Current or prior treatment with sacubitril and valsartan. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Novartis Investigative Site | Alpena | Michigan |
| United States | Novartis Investigative Site | Amarillo | Texas |
| United States | Novartis Investigative Site | Athens | Georgia |
| United States | Novartis Investigative Site | Atlantis | Florida |
| United States | Novartis Investigative Site | Augusta | Georgia |
| United States | Novartis Investigative Site | Aventura | Florida |
| United States | Novartis Investigative Site | Baltimore | Maryland |
| United States | Novartis Investigative Site | Baton Rouge | Louisiana |
| United States | Novartis Investigative Site | Beverly Hills | California |
| United States | Novartis Investigative Site | Birmingham | Alabama |
| United States | Novartis Investigative Site | Blue Ridge | Georgia |
| United States | Novartis Investigative Site | Bradenton | Florida |
| United States | Novartis Investigative Site | Bronx | New York |
| United States | Novartis Investigative Site | Buffalo | New York |
| United States | Novartis Investigative Site | Charlotte | North Carolina |
| United States | Novartis Investigative Site | Coeur d'Alene | Idaho |
| United States | Novartis Investigative Site | Coral Gables | Florida |
| United States | Novartis Investigative Site | Daytona Beach | Florida |
| United States | Novartis Investigative Site | Doral | Florida |
| United States | Novartis Investigative Site | Eatonton | Georgia |
| United States | Novartis Investigative Site | Eunice | Louisiana |
| United States | Novartis Investigative Site | Fairview Heights | Illinois |
| United States | Novartis Investigative Site | Fort Lauderdale | Florida |
| United States | Novartis Investigative Site | Greenville | North Carolina |
| United States | Novartis Investigative Site | Greenwich | Connecticut |
| United States | Novartis Investigative Site | Gurnee | Illinois |
| United States | Novartis Investigative Site | Hialeah | Florida |
| United States | Novartis Investigative Site | Hillsborough | New Jersey |
| United States | Novartis Investigative Site | Houston | Texas |
| United States | Novartis Investigative Site | Huntington Beach | California |
| United States | Novartis Investigative Site | Inverness | Florida |
| United States | Novartis Investigative Site | Jackson | Tennessee |
| United States | Novartis Investigative Site | Jacksonville | Florida |
| United States | Novartis Investigative Site | Jupiter | Florida |
| United States | Novartis Investigative Site | Lake Success | New York |
| United States | Novartis Investigative Site | Las Vegas | Nevada |
| United States | Novartis Investigative Site | Lenoir | North Carolina |
| United States | Novartis Investigative Site | Lincoln | Nebraska |
| United States | Novartis Investigative Site | Linden | New Jersey |
| United States | Novartis Investigative Site | Little Rock | Arkansas |
| United States | Novartis Investigative Site | Macon | Georgia |
| United States | Novartis Investigative Site | Manalapan | New Jersey |
| United States | Novartis Investigative Site | Manitowoc | Wisconsin |
| United States | Novartis Investigative Site | McKinney | Texas |
| United States | Novartis Investigative Site | McKinney | Texas |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | Novartis Investigative Site | Minden | Louisiana |
| United States | Novartis Investigative Site | Monroe | Louisiana |
| United States | Novartis Investigative Site | Mountain Lakes | New Jersey |
| United States | Novartis Investigative Site | Naples | Florida |
| United States | Novartis Investigative Site | Newark | Delaware |
| United States | Novartis Investigative Site | Newport Beach | California |
| United States | Novartis Investigative Site | Northridge | California |
| United States | Novartis Investigative Site | Norwalk | Connecticut |
| United States | Novartis Investigative Site | Omaha | Nebraska |
| United States | Novartis Investigative Site | Overland Park | Kansas |
| United States | Novartis Investigative Site | Owensboro | Kentucky |
| United States | Novartis Investigative Site | Owosso | Michigan |
| United States | Novartis Investigative Site | Richland | Washington |
| United States | Novartis Investigative Site | Richmond | Virginia |
| United States | Novartis Investigative Site | Rosedale | New York |
| United States | Novartis Investigative Site | Saginaw | Michigan |
| United States | Novartis Investigative Site | Saint Augustine | Florida |
| United States | Novartis Investigative Site | Santa Ana | California |
| United States | Novartis Investigative Site | Sherman | Texas |
| United States | Novartis Investigative Site | Slidell | Louisiana |
| United States | Novartis Investigative Site | Spokane | Washington |
| United States | Novartis Investigative Site | Stamford | Connecticut |
| United States | Novartis Investigative Site | Tomball | Texas |
| United States | Novartis Investigative Site | Trumbull | Connecticut |
| United States | Novartis Investigative Site | Van Nuys | California |
| United States | Novartis Investigative Site | Webster | Texas |
| United States | Novartis Investigative Site | Yardley | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change From Baseline in Aortic Characteristic Impedance at Week 12 | Aortic characteristic impedance, Zc, is the ratio of the change in pressure (dP)produced by a given change in flow (dQ) in early systole, i.e., Zc = dP/dQ. Zc is related directly to aortic wall stiffness and inversely to lumen area. | Baseline, Week 12 | |
| Secondary | Pearson Correlation Coefficient Between Change From Baseline in Aortic Characteristic Impedance and Biomarker Levels: B-type Natriuretic Peptide (BNP) During Both Trough and 4 Hours Post-dose at Week 4 | Pearson correlation coefficients between changes from baseline in aortic characteristic impedance (dyne x sec/cm5) and biomarker levels such as BNP (pg/ML) during both trough and 4 hours post-dose at Week 4 | Pre-dose and 4 hours post dose at week 4 | |
| Secondary | Pearson Correlation Coefficient Between Change From Baseline in Aortic Characteristic Impedance and Biomarker Levels: cGMP/U-creatinine During Both Trough and 4 Hours Post-dose at Week 4 | Pearson correlation coefficient between changes from baseline in aortic characteristic impedance (dyne x sec/cm5) and biomarker levels such as U-cGMP/U-creatinine ratio (nmol/mmol) during both trough and 4 hours post-dose at Week 4 | pre-dose and 4 hours post dose at week 4 | |
| Secondary | Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) | Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) | Baseline, Week 12 | |
| Secondary | Change From Baseline in Echocardiographic Measure: Global Longitudinal Strain | Parameter measured by echocardiography. | Baseline, Week 12 | |
| Secondary | Change From Baseline in Echocardiographic Measure: Left Atrial Volume Index (LAVi) | Parameter measured by echocardiography | Baseline, Week 12 | |
| Secondary | Change From Baseline in Echocardiographic Measure: Mitral Annular E' Velocity (Doppler Tissue Imaging) | Parameter measured by echocardiography | Baseline, Week 12 | |
| Secondary | Change From Basekine in Echocardiographic Measure: Mitral E/E' | Parameter measured by echocardiography | Baseline, Week 12 | |
| Secondary | Change From Baseline in Echocardiographic Measure: Left Ventricular Ejection Fraction (LVEF) | Parameter measured by echocardiography | Baseline, Week 12 | |
| Secondary | Change From Baseline in Echocardiographic Measure: Ventricular-vascular Coupling (Ea/Ees) | Parameter measured by echocardiography | Baseline, Week 12 | |
| Secondary | Change From Baseline in Echocardiographic Measure: Left Ventricular End Systolic Volume Index (LVESVi) | Parameter measured by echocardiography | Baseline, Week 12 | |
| Secondary | Change From Baseline in Echocardiographic Measure: Left Ventricular End Diastolic Volume Index (LVEDVi) | Parameter measured by echocardiography | Baseline, Week 12 |