Description of Tolerability of LCZ696 (Sacubitril / Valsartan) in Heart Failure With Reduced Ejection Fraction (HFrEF) Treated in Real Life Setting (PARASAIL)

Novartis

Status and phase: Completed; Phase 4

Conditions: Hearth Failure With Reduced Ejection Fraction (HFrEF)

Treatments: Drug: LCZ696 (sacubitril/valsartan)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02690974

CLCZ696BCA02

Details and patient eligibility

About

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.

Enrollment: 302 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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302 participants in 1 patient group

LCZ696 (sacubitril / valsartan)

Other group

Description:

All patients were initiated on either LCZ696 at 24 mg sacubitril / 26 mg valsartan or LCZ696 at 49 mg sacubitril / 51 mg valsartan bid for 2-4 weeks and were up-titrated to the next higher dose for another 2 - 4 weeks as applicable.

Treatment:

Drug: LCZ696 (sacubitril/valsartan)