A multicenter, randomized, double-blind, parallel group, active-controlled study to evaluate the efficacy and safety of LCZ696 compared to enalapril on morbidity and mortality in patients with chronic heart failure and reduced ejection fraction

Study ID
STU 012011-025

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • UT Southwestern University Hospital—St. Paul

Contact
Lynn Fernandez
214-645-8040
lynn.fernandez@utsouthwestern.edu

Principal Investigator
Alpesh Amin

Summary

This study is a multicenter, randomized, double-blind, parallel group, active controlled study to evaluate the superiority of LCZ696 to enalapril, on morbidity and mortality reduction in chronic heart failure patients (nYHa Class ii-iV) with reduced ejection fraction. The trial consists of two main periods: a single-blind run-in period, which will last from 5 to 10 weeks, and a double-blind run-in period, which is projected to last from 22 to 43 months.

There will be 15 local subjects consented, with approximately half (7) of the participants projected as screen failures and/or early withdrawals (during the run-in period). The goal of the study is to enroll a total of 7,980 patients worldwide at approximately 1200 centers. The study is projected to last from 23 to 45 months.

Participant Eligibility

1. Patients must give written informed consent before any assessment is performed.
2. Outpatients >= 18 years of age, male or female.
3. Patients with a diagnosis of CHF NYHA class II-IV and reduced ejection fraction:
o LVEF <= 35% at Visit 1 (any local measurement, made within the past 6 months using
echocardiography, MUGA, CT scanning, MRI or ventricular angiography is
acceptable, provided no subsequent measurement above 35%)
o BNP >= 150 pg/ml (or NT-proBNP >= 600 pg/ml) at Visit 1 OR BNP >= 100 pg/mL (or
NT-proBNP >= 400 pg/ml) at Visit 1 and a hospitalization for HF within the last 12
months
4. Patients must be on an ACEI or an ARB at a stable dose of at least enalapril 10 mg/d or
equivalent for at least 4 weeks before Visit 1
o For this protocol doses of other ACEIs considered to be equivalent to enalapril 10
mg/d include benazepril 20 mg/d, captopril 100 mg/d, cilazapril 2.5 mg/d, fosinopril
20 mg/d, lisinopril 10 mg/d, moexipril 7.5 mg/d, perindopril 4 mg/d, quinapril 20
mg/d, ramipril 5 mg/d, trandolapril 2 mg/d, and zofenopril 30 mg/d.
o For this protocol doses of ARBs considered to be equivalent to enalapril 10 mg/d
include candesartan 16 mg/d, eprosartan 400 mg/d, irbesartan 150 mg/d, losartan 50
mg/d, olmesartan 10 mg/d, telmisartan 40 mg/d, and valsartan 160 mg/d.
5. Patients must be treated with a [BETA]-blocker, unless contraindicated or not tolerated, at a
stable dose for at least 4 weeks prior to Visit 1 (reason should be documented for patients
not on CHF target doses per local guidelines, or in absence of that medication).
6. An aldosterone antagonist should also be considered in all patients, taking account of renal
function, serum potassium and tolerability. If given, the dose of aldosterone antagonist
should be optimized according to guideline recommendations and patient tolerability, and
should be stable for at least 4 weeks prior to Visit 1. Other evidence-based therapy for
heart failure should also be considered e.g. cardiac resynchronization therapy and an
implantable cardioverter-defibrillator in selected patients, as recommended by guidelines.