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

Primary Purpose

Hearth Failure With Reduced Ejection Fraction (HFrEF)

Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
LCZ696 (sacubitril/valsartan)
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Hearth Failure With Reduced Ejection Fraction (HFrEF) focused on measuring HFrEF,, ACEi,, ACE inhibitor,, ARBs,, systolic heart failure,, chronic heart failure,, CHF,, reduced EF,, Ejection Fraction

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

LCZ696 (sacubitril / valsartan)

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Percentage of Participants on LCZ696 200 mg Bid at Month 12
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 12. Only descriptive analysis done.
Percentage of Participants Requiring Down-titration From LCZ696 200 mg
The impact of the titration scheme on the tolerability of patients maintained on LCZ696 97 mg sacubitril / 103 mg valsartan bid was defined as the percentage of patients on LCZ696 200mg requiring down-titration. Only descriptive analysis done.
Percentage of Participants With Down-titration Changes From LCZ696 200 mg During 12 Months of Treatment
The impact of the titration scheme on the tolerability of patients maintained on LCZ696 97 mg sacubitril / 103 mg valsartan bid was defined as the number of down-titration during the 12 months treatment period. Dow-titration schemes considered for the analysis are 200 mg to 100 mg; 100 mg to 50 mg; and 50 mg to 0 mg (i.e. treatment discontinuation). The down-titration scheme of 50mg to 0 mg was taken in account in this analysis to ensure to reflect all actual changes in dose. Only descriptive analysis done.
Change From Baseline in the Six Minute Walk Test (6MWT) at Month 6 and Month 12
The impact of LCZ696 on functional exercise capacity was measured by the Six Minute Walk Test at 6 and 12 months. The 6MWT measures the distance an individual is able to walf over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. Only descriptive analysis done.
Time to Each Up-titration to LCZ696 100 mg and LCZ696 200 mg
To describe the time of up-titration for each dose (24 mg sacubitril / 26 mg valsartan bid and 49 mg sacubitril / 51 mg valsartan bid) of LCZ696. Only descriptive analysis done.
Median Time to Reach LCZ696 200 mg
To describe the time of up-titration for each dose (24 mg sacubitril / 26 mg valsartan bid and 49 mg sacubitril / 51 mg valsartan bid) of LCZ696. Only descriptive analysis done.
Percentage of Participants on Guideline Recommended Dose of Beta-blockers and MRAs Over Time
To describe the adherence to guideline recommended dosing of beta-blockers and MRAs at 6 and 12 months of treatment of LCZ696. Only descriptive analysis done.

Full Information

First Posted
February 15, 2016
Last Updated
March 5, 2019
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02690974
Brief Title
Description of Tolerability of LCZ696 (Sacubitril / Valsartan) in Heart Failure With Reduced Ejection Fraction (HFrEF) Treated in Real Life Setting
Acronym
PARASAIL
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

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
March 8, 2016 (Actual)
Primary Completion Date
June 7, 2017 (Actual)
Study Completion Date
November 29, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hearth Failure With Reduced Ejection Fraction (HFrEF)
Keywords
HFrEF,, ACEi,, ACE inhibitor,, ARBs,, systolic heart failure,, chronic heart failure,, CHF,, reduced EF,, Ejection Fraction

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
302 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LCZ696 (sacubitril / valsartan)
Arm Type
Other
Arm 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.
Intervention Type
Drug
Intervention Name(s)
LCZ696 (sacubitril/valsartan)
Intervention Description
All patients were treated with the LCZ696 (sacubitril and valsartan) tablets
Primary Outcome Measure Information:
Title
Percentage of Participants on LCZ696 200 mg Bid at Month 6
Description
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.
Time Frame
Month 6
Secondary Outcome Measure Information:
Title
Percentage of Participants on LCZ696 200 mg Bid at Month 12
Description
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 12. Only descriptive analysis done.
Time Frame
Month 12
Title
Percentage of Participants Requiring Down-titration From LCZ696 200 mg
Description
The impact of the titration scheme on the tolerability of patients maintained on LCZ696 97 mg sacubitril / 103 mg valsartan bid was defined as the percentage of patients on LCZ696 200mg requiring down-titration. Only descriptive analysis done.
Time Frame
Month 12
Title
Percentage of Participants With Down-titration Changes From LCZ696 200 mg During 12 Months of Treatment
Description
The impact of the titration scheme on the tolerability of patients maintained on LCZ696 97 mg sacubitril / 103 mg valsartan bid was defined as the number of down-titration during the 12 months treatment period. Dow-titration schemes considered for the analysis are 200 mg to 100 mg; 100 mg to 50 mg; and 50 mg to 0 mg (i.e. treatment discontinuation). The down-titration scheme of 50mg to 0 mg was taken in account in this analysis to ensure to reflect all actual changes in dose. Only descriptive analysis done.
Time Frame
Month 12
Title
Change From Baseline in the Six Minute Walk Test (6MWT) at Month 6 and Month 12
Description
The impact of LCZ696 on functional exercise capacity was measured by the Six Minute Walk Test at 6 and 12 months. The 6MWT measures the distance an individual is able to walf over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. Only descriptive analysis done.
Time Frame
Baseline, Month 6 and Month 12
Title
Time to Each Up-titration to LCZ696 100 mg and LCZ696 200 mg
Description
To describe the time of up-titration for each dose (24 mg sacubitril / 26 mg valsartan bid and 49 mg sacubitril / 51 mg valsartan bid) of LCZ696. Only descriptive analysis done.
Time Frame
Baseline, Week 2, Week 4, Month 3, Month 6 and Month 12
Title
Median Time to Reach LCZ696 200 mg
Description
To describe the time of up-titration for each dose (24 mg sacubitril / 26 mg valsartan bid and 49 mg sacubitril / 51 mg valsartan bid) of LCZ696. Only descriptive analysis done.
Time Frame
Baseline, Week 2, Week 4, Month 3, Month 6 and Month 12
Title
Percentage of Participants on Guideline Recommended Dose of Beta-blockers and MRAs Over Time
Description
To describe the adherence to guideline recommended dosing of beta-blockers and MRAs at 6 and 12 months of treatment of LCZ696. Only descriptive analysis done.
Time Frame
Baseline, Month 6 and Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: 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. Key Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T5H 3V9
Country
Canada
Facility Name
Novartis Investigative Site
City
New Westminster
State/Province
British Columbia
ZIP/Postal Code
V3L 3W4
Country
Canada
Facility Name
Novartis Investigative Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
Novartis Investigative Site
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R2H 2A6
Country
Canada
Facility Name
Novartis Investigative Site
City
Moncton
State/Province
New Brunswick
ZIP/Postal Code
E1C 2Z3
Country
Canada
Facility Name
Novartis Investigative Site
City
Moncton
State/Province
New Brunswick
ZIP/Postal Code
E1G 1A7
Country
Canada
Facility Name
Novartis Investigative Site
City
St. John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1B 3V6
Country
Canada
Facility Name
Novartis Investigative Site
City
Burlington
State/Province
Ontario
ZIP/Postal Code
L7M 4Y1
Country
Canada
Facility Name
Novartis Investigative Site
City
Cambridge
State/Province
Ontario
ZIP/Postal Code
N1R 6V6
Country
Canada
Facility Name
Novartis Investigative Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Novartis Investigative Site
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L5K 2L3
Country
Canada
Facility Name
Novartis Investigative Site
City
Newmarket
State/Province
Ontario
ZIP/Postal Code
L3Y 2P6
Country
Canada
Facility Name
Novartis Investigative Site
City
Newmarket
State/Province
Ontario
ZIP/Postal Code
L3Y 8C3
Country
Canada
Facility Name
Novartis Investigative Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
Facility Name
Novartis Investigative Site
City
Peterborough
State/Province
Ontario
ZIP/Postal Code
K9J 0B2
Country
Canada
Facility Name
Novartis Investigative Site
City
Sarnia
State/Province
Ontario
ZIP/Postal Code
N7T 4X3
Country
Canada
Facility Name
Novartis Investigative Site
City
Scarborough
State/Province
Ontario
ZIP/Postal Code
M1E 5E9
Country
Canada
Facility Name
Novartis Investigative Site
City
Scarborough
State/Province
Ontario
ZIP/Postal Code
M1P 2V5
Country
Canada
Facility Name
Novartis Investigative Site
City
Sudbury
State/Province
Ontario
ZIP/Postal Code
P3E 3B8
Country
Canada
Facility Name
Novartis Investigative Site
City
Sudbury
State/Province
Ontario
ZIP/Postal Code
P3E 5M9
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6R 1B5
Country
Canada
Facility Name
Novartis Investigative Site
City
Waterloo
State/Province
Ontario
ZIP/Postal Code
N2T 0C1
Country
Canada
Facility Name
Novartis Investigative Site
City
Weston
State/Province
Ontario
ZIP/Postal Code
M9N 1W4
Country
Canada
Facility Name
Novartis Investigative Site
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2G8
Country
Canada
Facility Name
Novartis Investigative Site
City
Joliette
State/Province
Quebec
ZIP/Postal Code
J6E 6J2
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 3Y7
Country
Canada
Facility Name
Novartis Investigative Site
City
St-Jean-sur-Richelieu
State/Province
Quebec
ZIP/Postal Code
J3A 1J2
Country
Canada
Facility Name
Novartis Investigative Site
City
Terrebonne
State/Province
Quebec
ZIP/Postal Code
J6V 2H2
Country
Canada
Facility Name
Novartis Investigative Site
City
Brossard
ZIP/Postal Code
J4Z 2K9
Country
Canada
Facility Name
Novartis Investigative Site
City
Hamilton
ZIP/Postal Code
L8L 0A9
Country
Canada
Facility Name
Novartis Investigative Site
City
Quebec
ZIP/Postal Code
GIV 4G5
Country
Canada
Facility Name
Novartis Investigative Site
City
St-Lambert
ZIP/Postal Code
J4P 2J2
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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