Comparing ARNI With ACE Inhibitor on Endothelial Function

• Status: Withdrawn
• Trial end date: 2019-08-01
• Target enrollment: 0
• Participant gender: All

Summary

PARADOR is multisite, randomized, double-blind, phase IV clinical trial to compare the effect of sacubitril/valsartan (Entresto™) to enalapril (Vasotec®) on blood vessel function in subjects with heart failure with reduced ejection fraction (HFREF).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital; University of Wisconsin, Madison
• Collaborators: Brigham and Women's Hospital; Novartis Pharmaceuticals
• Treatments: Angiotensin-Converting Enzyme Inhibitors; Enalapril; Enalaprilat; LCZ 696; Valsartan

Criteria

Inclusion Criteria:

• Willing to provide written informed consent

• Willing to comply with all study procedures and be available for the duration of the study

• Male or female, at least 18 years of age

• Documented diagnosis of heart failure

• Documented history of left ventricular ejection fraction < 40% in the 6 months of randomization

• NYHA functional class II or III

• Current treatment with an ACEI at a stable dose of at least enalapril 5 mg twice daily or equivalent for at least 30 days

• Stable heart failure medications (ACEi, +/-beta blocker, +/-mineralocorticoid receptor antagonist) for the past 30 days (with the exception of diuretics) Females of childbearing potential must have a negative urine pregnancy test prior to randomization and agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to randomization, for the duration of study participation, and for 7 days following completion of therapy.

A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

Exclusion Criteria:

• Documented or self-reported history of hereditary or idiopathic angioedema

• History of acute coronary syndrome, cardiac bypass procedure, stroke, or transient ischemic attack within three months of randomization

• Placement of a biventricular pacemaker device within 6 months of randomization

• History of hypersensitivity or allergy to any of the study drugs or drugs of similar chemical classes

• Current use of sacubitril/valsartan

• Previous intolerance to ACE inhibitors

• Baseline Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m2 per the Modification of Diet in Renal Disease (MDRD) formula

• History of bilateral renal artery stenosis

• History of hepatic dysfunction

• Baseline serum potassium greater than 5.2 mmol/L

• Baseline systolic blood pressure less than 110 mmHg or greater than 180 mmHg

• Enrolled in another clinical trial or has used of any investigational drugs, biologics, or devices within 30 days prior to randomization

• Women who are pregnant or breast-feeding

• Not suitable for study participation due to other reasons at the discretion of the investigator