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

NCT02690974 | Completed Phase 4 Results

• 1 other identifier: CLCZ696BCA02
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 32

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.

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants on LCZ696 200 mg Bid at Month 6

  The tolerability of LCZ696 was defined as the percentage of patients on LCZ696 at the dose of 97 mg sacubitril / 103 mg valsartan twice daily (bid) who did not experience down titration or treatment discontinuation because of adverse events while on this dose at month 6. Only descriptive analysis done.

  Month 6

Secondary Outcomes (7)

• Percentage of Participants on LCZ696 200 mg Bid at Month 12

  Month 12

• Percentage of Participants Requiring Down-titration From LCZ696 200 mg

  Month 12

• Percentage of Participants With Down-titration Changes From LCZ696 200 mg During 12 Months of Treatment

  Month 12

• Change From Baseline in the Six Minute Walk Test (6MWT) at Month 6 and Month 12

  Baseline, Month 6 and Month 12

• Time to Each Up-titration to LCZ696 100 mg and LCZ696 200 mg

  Baseline, Week 2, Week 4, Month 3, Month 6 and Month 12

Study Arms (1)

LCZ696 (sacubitril / valsartan)

OTHER

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.

Drug: LCZ696 (sacubitril/valsartan)

Interventions

LCZ696 (sacubitril/valsartan) DRUG

All patients were treated with the LCZ696 (sacubitril and valsartan) tablets

LCZ696 (sacubitril / valsartan)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Symptomatic hypotension and/or a SBP \< 100 mmHg at baseline visit.
• Estimated GFR \< 30 mL/min/1.73m\^2 as measured by the simplified Modification of Diet in Renal Disease (MDRD) formula at baseline visit.
• Known history of angioedema related to previous ACEI or ARBs therapy, or history of hereditary or idiopathic angioedema.
• Requirement of concomitant treatment with both ACEIs and ARBs.
• Concurrent participation in other clinical trials or receiving other investigational drugs within 30 days of enrollment.
• Hypersensitivity to the active substances, sacubitril or valsartan, or to any of the excipients.
• 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).
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (32)

Novartis Investigative Site

Edmonton, Alberta, T5H 3V9, Canada

Location

Novartis Investigative Site

New Westminster, British Columbia, V3L 3W4, Canada

Location

Novartis Investigative Site

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Novartis Investigative Site

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Novartis Investigative Site

Moncton, New Brunswick, E1C 2Z3, Canada

Location

Novartis Investigative Site

Moncton, New Brunswick, E1G 1A7, Canada

Location

Novartis Investigative Site

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Novartis Investigative Site

Burlington, Ontario, L7M 4Y1, Canada

Location

Novartis Investigative Site

Cambridge, Ontario, N1R 6V6, Canada

Location

Novartis Investigative Site

Greater Sudbury, Ontario, P3E 3B8, Canada

Location

Novartis Investigative Site

Greater Sudbury, Ontario, P3E 5M9, Canada

Location

Novartis Investigative Site

London, Ontario, N6A 5A5, Canada

Location

Novartis Investigative Site

Mississauga, Ontario, L5K 2L3, Canada

Location

Novartis Investigative Site

Newmarket, Ontario, L3Y 2P6, Canada

Location

Novartis Investigative Site

Newmarket, Ontario, L3Y 8C3, Canada

Location

Novartis Investigative Site

Ottawa, Ontario, K1Y 4W7, Canada

Location

Novartis Investigative Site

Peterborough, Ontario, K9J 0B2, Canada

Location

Novartis Investigative Site

Sarnia, Ontario, N7T 4X3, Canada

Location

Novartis Investigative Site

Scarborough Village, Ontario, M1E 5E9, Canada

Location

Novartis Investigative Site

Scarborough Village, Ontario, M1P 2V5, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M6R 1B5, Canada

Location

Novartis Investigative Site

Waterloo, Ontario, N2T 0C1, Canada

Location

Novartis Investigative Site

Weston, Ontario, M9N 1W4, Canada

Location

Novartis Investigative Site

Greenfield Park, Quebec, J4V 2G8, Canada

Location

Novartis Investigative Site

Joliette, Quebec, J6E 6J2, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H1T 3Y7, Canada

Location

Novartis Investigative Site

Saint-Jean-sur-Richelieu, Quebec, J3A 1J2, Canada

Location

Novartis Investigative Site

Terrebonne, Quebec, J6V 2H2, Canada

Location

Novartis Investigative Site

Brossard, J4Z 2K9, Canada

Location

Novartis Investigative Site

Hamilton, L8L 0A9, Canada

Location

Novartis Investigative Site

Québec, GIV 4G5, Canada

Location

Novartis Investigative Site

Saint-Lambert, J4P 2J2, Canada

Location

MeSH Terms

Conditions

Heart Failure, Systolic

Interventions

sacubitril and valsartan sodium hydrate drug combination; sacubitril; Valsartan

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2016
• First Posted: February 24, 2016
• Study Start: March 8, 2016
• Primary Completion: June 7, 2017
• Study Completion: November 29, 2017
• Last Updated: June 7, 2019
• Results First Posted: June 7, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (32)