Comparing ARNI With ACE Inhibitor on Endothelial Function

NCT03119623 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: 2017P002389/PHS
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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).

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

Heart Failure; Endothelial function; Brachial Artery Reactivity Test; Sacubitril/Valsartan; Enalapril; HFREF

Outcome Measures

Primary Outcomes (1)

• Flow Mediated Vasodilation

  To test the hypothesis that sacubitril/valsartan will improve endothelial function compared to enalapril, evidenced by increased flow mediated vasodilation (FMD) measured by brachial artery reactivity test (BART)

  At study treatment completion (10 weeks)

Secondary Outcomes (1)

• B-type natriuretic peptide

  At study treatment completion (10 weeks)

Study Arms (2)

Sacubitril/Valsartan

ACTIVE COMPARATOR

Sacubitril/valsartan 100mg (Dose Level 1) titrated up if tolerated to 200 mg twice daily (Dose Level 2)

Drug: sacubitril/valsartan

Enalapril

ACTIVE COMPARATOR

Enalapril 5mg (Dose Level 1) titrated up if tolerated to 10mg twice daily (Dose Level 2)

Drug: Enalapril

Interventions

sacubitril/valsartan DRUG

Sacubitril/valsartan 100mg titrated up to sacubitril/valsartan 200mg

Also known as: ENTRESTO, LCZ696

Sacubitril/Valsartan

Enalapril DRUG

enalapril 5mg, titrated up to 10mg po BID

Also known as: Vasotec

Enalapril

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Novartis Pharmaceuticals: collaborator

MeSH Terms

Conditions

Heart Failure

Interventions

sacubitril and valsartan sodium hydrate drug combination; Enalapril; Enalaprilat

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Orly Vardeny, PharmD, MS

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 18, 2017
• Study Start: June 1, 2017
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: October 11, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share