Clinical trial NCT02690974: Description of Tolerability of LCZ696 (Sacubitril / Valsartan) in Heart Failure With Reduced Ejection Fraction (HFrEF) Treated in Real Life Setting
Official title: Prospective, Multi-center, Open lAbel, Post-appRovAl Study AImed at Characterizing the Use of LCZ696 at 97 mg Sacubitril / 103 mg Valsartan Bid in Patients With HFrEF
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hearth Failure With Reduced Ejection Fraction (HFrEF)
Keywords: HFrEF,
ACEi,
ACE inhibitor,
ARBs,
systolic heart failure,
chronic heart failure,
CHF,
reduced EF,
Ejection Fraction
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-02-24
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The primary purpose of the study was to describe the tolerability of treatment with the optimal dose of LCZ696 (97 mg sacubitril / 103 mg valsartan bid), over six (6) months, in patients with heart failure with reduced ejection fraction (HFrEF) in Canada.

The study was also to describe the overall tolerability, effectiveness and safety of LCZ696 for the management of HFrEF over 12 months of treatment, as well as describe the patterns of LCZ696 up and down dose titrations occurring during the management of patients with HFrEF.


Eligibility criteria: Key Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. Age ≥ 18 years and ≤ 80 years.
3. Males or females.
4. Diagnosis of Heart Failure NYHA class II-III.
5. Diagnosis of Heart Failure with reduced Ejection Fraction (LVEF =\< 40%) and NYHA class II or III.
6. Stable on any dose of ACEI or ARB prior to enrolment in the study
7. Stable on any dose of a beta-blocker prior to enrolment in the study.
8. Eligible for treatment with LCZ696 as per Canadian product monograph.
9. Treated as an outpatient.
10. Signed an informed consent agreeing to participate in the study.

Key Exclusion Criteria:

1. Symptomatic hypotension and/or a SBP \< 100 mmHg at baseline visit.
2. Estimated GFR \< 30 mL/min/1.73m\^2 as measured by the simplified Modification of Diet in Renal Disease (MDRD) formula at baseline visit.
3. Known history of angioedema related to previous ACEI or ARBs therapy, or history of hereditary or idiopathic angioedema.
4. Requirement of concomitant treatment with both ACEIs and ARBs.
5. Concurrent participation in other clinical trials or receiving other investigational drugs within 30 days of enrollment.
6. Hypersensitivity to the active substances, sacubitril or valsartan, or to any of the excipients.
7. Concomitant use of aliskiren-containing drugs in patients with diabetes mellitus (type 1 or type 2) or moderate to severe renal impairment (GFR \<60ml/min/1.73m\^2).
8. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
9. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
11. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. Effective contraception methods are described in the protocol.

Primary outcomes:
measure: Percentage of Participants on LCZ696 200 mg Bid at Month 6
timeFrame: Month 6
Secondary outcomes:
measure: Percentage of Participants on LCZ696 200 mg Bid at Month 12
timeFrame: Month 12
measure: Percentage of Participants Requiring Down-titration From LCZ696 200 mg
timeFrame: Month 12
measure: Percentage of Participants With Down-titration Changes From LCZ696 200 mg During 12 Months of Treatment
timeFrame: Month 12
measure: Change From Baseline in the Six Minute Walk Test (6MWT) at Month 6 and Month 12
timeFrame: Baseline, Month 6 and Month 12
measure: Time to Each Up-titration to LCZ696 100 mg and LCZ696 200 mg
timeFrame: Baseline, Week 2, Week 4, Month 3, Month 6 and Month 12
measure: Median Time to Reach LCZ696 200 mg
timeFrame: Baseline, Week 2, Week 4, Month 3, Month 6 and Month 12
measure: Percentage of Participants on Guideline Recommended Dose of Beta-blockers and MRAs Over Time
timeFrame: Baseline, Month 6 and Month 12
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: New Westminster
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Novartis Investigative Site
state: Manitoba
city: Moncton
country: Canada
facility: Novartis Investigative Site
state: New Brunswick
city: Moncton
country: Canada
facility: Novartis Investigative Site
state: New Brunswick
city: St. John's
country: Canada
facility: Novartis Investigative Site
state: Newfoundland and Labrador
city: Burlington
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Cambridge
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Mississauga
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Newmarket
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Newmarket
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Peterborough
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Sarnia
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Scarborough
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Scarborough
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Sudbury
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Sudbury
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Waterloo
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Weston
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Greenfield Park
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Joliette
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: St-Jean-sur-Richelieu
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Terrebonne
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Brossard
country: Canada
facility: Novartis Investigative Site
city: Hamilton
country: Canada
facility: Novartis Investigative Site
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: St-Lambert
country: Canada
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: